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Emgality ® ▼ (galcanezumab)
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What was the incidence, duration and treatment of injection site reactions in patients treated with Emgality® (galcanezumab)?
Injection site-related adverse reactions were the most frequently reported ARs in the migraine phase 3 studies. The majority of injection site reactions were mild to moderate and on average resolved within 5 days. Comfort measures were allowed.
Content overview
- Injection site-related adverse drug reactions from the Summary of Product Characteristics
- Injection site-related adverse events in galcanezumab migraine prevention clinical studies
- Incidence of injection-site-related adverse events
- Serious adverse events and discontinuations due to injection-site-related AEs
- Characterization of injection site-related adverse events
- The incidence of injection-site–related AEs reported over the treatment course
- Injection-site reactions by antidrug antibody status
- Prevention and management of injection site-related adverse events in galcanezumab phase 3 migraine prevention clinical studies
- Postmarketing spontaneous reports related to injection-site-related AEs
- References
- Appendix
-
Injection site-related adverse drug reactions from the Summary of Product Characteristics
Injection site pain or reactions
The reported adverse drug reactions for 120 mg and 240 mg in migraine clinical trials were
- injection site pain (10.1 %/11.6 %),
- injection site reactions (9.9 %/14.5 %1
- The recommended dose is 120 mg galcanezumab injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose.1 Please note that the results of a maintenance dose of 240 mg galcanezumab once monthly are also included in this response. Even though this dose has been tested in pivotal studies, it has not been approved and therefore is not recommended.
With regard to Injection site reactions, the most frequently reported terms (≥ 1 %) were:
- Injection site reaction
- Injection site erythema
- Injection site pruritus
- Injection site bruising
- Injection site swelling.1
The majority of reactions related to the injection site were mild to moderate and less than 0.5 % of patients exposed to galcanezumab during the phase 3 studies discontinued the treatment due to an injection site reaction.1
The majority of injection site reactions were reported within 1 day and on average resolved within 5 days. In 86 % of the patients reporting injection site pain, the reaction occurred within 1 hour of injection and resolved on average in 1 day.1
One percent of the patients exposed to galcanezumab during the phase 3 studies experienced severe pain at the injection site.1
Pruritus
Pruritus is a common adverse reaction of galcanezumab. Pruritus was reported by 0.7 % and 1.2 % of patients with 120 mg and 240 mg galcanezumab, respectively.1
Urticaria
Urticaria is an uncommon adverse reaction of galcanezumab. Urticaria was reported by 0.3 % and 0.1 % of patients with 120 mg and 240 mg galcanezumab, respectively.1
While urticaria is uncommon, serious cases of urticaria have been reported in galcanezumab clinical studies. 1
Back to Content overview.
Injection site-related adverse events in galcanezumab migraine prevention clinical studies
Please refer to the Evaluation of injection-site–related adverse events in the galcanezumab migraine prevention clinical studies for information on
- galcanezumab clinical trials for migraine prevention
- administration of galcanezumab during the clinical trials (including device used).
Incidence of injection-site-related adverse events
Injection-site–related adverse events (AEs) occurred in significantly more galcanezumab-treated patients than placebo in
- EVOLVE-1, EVOLVE-2, and REGAIN (20.5% galcanezumab pooled vs 12.6% placebo, Summary of Injection-Site–Related AEs During Phase 3 Double-Blind Treatment: EVOLVE-1, EVOLVE-2, REGAIN)2 and
- the phase 2 study in Japanese patients (32.8% galcanezumab pooled vs 5.7% placebo, Summary of Injection-Site–Related AEs: Phase 2 Study in Japanese Patients With Episodic Migraine).3
In the CONQUER study, injection-site–related AEs occurred more frequently in placebo-treated patients (10%) than galcanezumab-treated patients (6.9%) during the double-blind treatment phase (Summary of Injection-Site–Related AEs: CONQUER Study).4
Injection-site–related AEs were reported by 21.8% of galcanezumab-treated patients in the long-term analysis set (REGAIN and CGAJ).2
Most commonly reported injection site-related adverse events
The most commonly reported injection-site–related AE was
These results are summarized in Summary of Injection-Site–Related AEs During Phase 3 Double-Blind Treatment: EVOLVE-1, EVOLVE-2, REGAIN, Summary of Injection-Site–Related AEs: CONQUER Study, and Summary of Injection-Site–Related AEs: Phase 2 Study in Japanese Patients With Episodic Migraine in the Appendix.
Serious adverse events and discontinuations due to injection-site-related AEs
No serious adverse events (SAEs) related to injection sites were reported in any of the studies (EVOLVE-1, EVOLVE-2, REGAIN, CONQUER, CGAJ, or CGAN).2,3,5-7
Discontinuations due to injection-site–related AEs in galcanezumab-treated patients occurred
No placebo-treated patients discontinued due to injection-site–related AEs.2,5
In the EVOLVE-1, EVOLVE-2, and REGAIN studies, injection-site–related AEs resulting in study discontinuation were
- moderate unspecified injection-site reaction (n=4)
- moderate injection-site pain (n=1)
- severe injection site-erythema (n=1), and
- moderate injection-site swelling (n=1).2
All discontinuations due to injection-site–related AEs resolved without sequelae.3
During the CONQUER study,
In the long-term analysis set, 9 patients discontinued due to injection-site–related AEs during open-label treatment. All discontinuations were observed following multiple doses of galcanezumab.2
In the CGAN study, 2 galcanezumab-treated patients (240 mg) reported severe injection-site reactions, but only 1 patient discontinued as a result. These were
- injection-site erythema and injection-site pruritus (discontinued due to the injection-site erythema), and
- injection-site pruritus, injection-site erythema, and injection-site induration (did not discontinue).8
Characterization of injection site-related adverse events
The majority of patients reporting injection-site–related AEs (excluding pain) had events that
In EVOLVE-1, EVOLVE-2, and REGAIN, all the 67 galcanezumab-treated patients who reported a nonspecified AE of injection-site reaction had at least 1 follow-up form completed to further characterize the unspecified injection site reaction: Characterization of Nonspecific Injection-Site Reactions Reported by Galcanezumab-Treated Patients During Double-Blind Treatment: EVOLVE-1, EVOLVE-2, REGAIN.2
GMB 120 mg |
GMB 240 mg |
|
Pain |
81% |
71% |
Itching |
59% |
60% |
Rash or redness |
59% |
84% |
Hardening of the injection site |
59% |
44% |
Abbreviation: GMB = galcanezumab.
aA nonspecified adverse event of injection-site reaction: some sites recorded the adverse event of “injection-site reaction” without further qualification while others were more specific in recording the symptom the patient reported at the site of the injection.
In CONQUER, each injection-site reaction was characterized based on a series of follow-up questions. Overall, 12.5% of galcanezumab-treated patients reported an injection-site reaction which was assessed using the injection-site reaction follow-up form: Characterization of Injection-Site Reactions Reported by Galcanezumab-Treated Patients in the CONQUER Study.7 More details were collected on the follow-up questions in the CONQUER study compared to the EVOLVE-1, EVOLVE-2, and REGAIN studies.
Injection-Site Reaction |
GMB-Treated Timea |
Patients with >1 record of ISR follow-up form |
57 (12.47) |
Pain |
|
Mild |
27 (5.9) |
Moderate |
8 (1.8) |
Severe |
2 (0.4) |
Erythema |
|
Very mild |
20 (4.4) |
Clearly red |
17 (3.7) |
Bright red |
3 (0.7) |
Pruritus |
|
Mild |
15 (3.3) |
Moderate |
3 (0.7) |
Severe |
1 (0.2) |
Induration |
|
Barely noticeable |
10 (2.2) |
Slight |
3 (0.7) |
Moderate |
5 (1.1) |
Severe |
3 (0.7) |
Edema |
|
Mild |
7 (1.5) |
Moderate |
5 (1.1) |
Severe |
5 (1.1) |
Abbreviations: GMB = galcanezumab; ISR = injection-site reaction.
aPatients were treated for up to 6 months with GMB (3 months double-blind/3 months open-label) or up to 3 months GMB (3 months placebo in double-blind/3 months GMB in open-label).
The incidence of injection-site–related AEs reported over the treatment course
In the CONQUER study, most patients received either 3 or 6 monthly injections over the course of 6 months, and the reporting of injection-site reactions did not increase with the number of doses.7
In the long-term analysis set, the reporting of injection-site reactions (excluding pain) by galcanezumab-treated patients did not increase with multiple dose administrations. Overall, 81% of patients received 9 doses or more of galcanezumab and most patients reported 1 to 3 events with monthly injections over 9 to 12 months.2
Top 4 Injection-Site Reactions and Severity in Galcanezumab-Treated Patients in Study CGAJ: https://www.kaltura.com/tiny/9t3qu illustrates the top 4 injection-site reactions (including severity) reported by galcanezumab-treated patients in the 12-month open-label safety study CGAJ.3
Note: This animation depicts injection-site reactions over time from study CGAJ and is not representative of injection-site reaction rates in all galcanezumab migraine prevention studies.
Injection-site reactions by antidrug antibody status
A post hoc analysis of EVOLVE-1, EVOLVE-2, REGAIN, and CGAJ studies reported no evidence that injection-site–related AEs were mediated by treatment-emergent anti-drug antibodies (TE ADA) in galcanezumab-treated patients. No specific injection-site–related AEs were reported exclusively in TE ADA+ patients.2,10
In TE ADA+ patients who reported injection-site–related AEs (Injection-Site–Related AEs and ADA in Galcanezumab-Treated Patients: Cases That Met Flagging for Further Review in Phase 3 Migraine Prevention Studies)
- 1 patient reported injection-site inflammation before the development of TE ADA which did not recur after the detection of titer increase of antibodies, and
- 2 patients had already detectable TE ADA before reporting injection-site rash.10
Preferred Term |
TE ADA Status |
N |
n (%) |
Injection-site rash |
Yes |
92 |
2 (2.2) |
No |
1562 |
10 (0.6) |
|
Injection-site inflammation |
Yes |
92 |
1 (1.1) |
No |
1562 |
1 (0.1) |
Abbreviations: ADA = anti-drug antibodies; AE = adverse event; N = number of patients in the analysis population; n = number of patients within each specific category; TE ADA = treatment-emergent anti-drug antibody.
aCriteria for case level review were based on odds ratio and p value from the Cochran-Mantel-Haenszel test that compared the proportions of patients with ≥1 preferred term related to injection-sites between TE ADA+ and TE ADA- patients, stratified by study. Events with an odds ratio >2.0 or p≤.05 met flagging criteria for further review.
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Prevention and management of injection site-related adverse events in galcanezumab phase 3 migraine prevention clinical studies
Safe practices for administering subcutaneous (SQ) injections include
- leaving the medication to sit at room temperature for 30 minutes prior to injection
- washing hands
- cleaning and drying the site prior to injection
- rotation of injection sites
- not injecting into areas where the skin is tender, bruised, red, or hard, and
- not massaging or rubbing the site after injection.3,11,12
Comfort measures used at injection sites
In the CONQUER study, staff were encouraged to administer comfort measures, such as cold compress, ice pack, or topical anesthetic cream, to the injection site prior to or after the injection at their clinical discretion as needed.7
The percentage of patients who used comfort measures around the time of injection was low and similar between treatment groups during double-blind treatment: Comfort Measures Used at Injection Sites During Double-Blind Treatment: CONQUER. The most frequently used comfort measure was application of an ice pack.3
|
PBO |
GMB 120 mg |
Comfort measures used before injection |
12 (1.3) |
15 (1.6) |
Ice pack |
10 (1.1) |
15 (1.6) |
Cold compress |
2 (0.2) |
0 (0.0) |
Topical anesthetic or analgesic cream |
0 (0.0) |
0 (0.0) |
Comfort measures used after injection |
23 (2.5) |
29 (3.2) |
Ice pack |
19 (2.1) |
27 (2.9) |
Cold compress |
4 (0.4) |
2 (0.2) |
Topical anesthetic or analgesic cream |
0 (0.0) |
0 (0.0) |
Abbreviations: GMB = galcanezumab; M = number of injections used for the analysis population; PBO = placebo.
Although management of injection-site–related AEs was not outlined in the phase 3 study protocols (EVOLVE-1, EVOLVE-2, REGAIN, CGAJ for migraine prevention or CGAL, CGAM, and CGAR for cluster headache), premedication was not prohibited.3
Concomitant medications including acetaminophen (paracetamol) and nonsteroidal anti-inflammatory drugs were permitted. Other concomitant medications such as topical steroids and topical or oral antihistamines were not prohibited. The use of oral steroids was prohibited.3
Management of injection-site–related AEs in the EVOLVE-1, EVOLVE-2, REGAIN, CGAJ, CGAL, CGAM, and CGAR studies was at the discretion of the study investigators.3 The decision whether to premedicate a patient prior to galcanezumab injection should be made at the discretion of the prescribing physician.
Factors for injection site pain and adverse events
Injection-site pain and AEs following SQ injection might vary depending on patient-related factors, properties of the compound, and the cellular dynamics at the site of injection.2,13 Examples include
- injection speed (injection-site pain with fast injections)
- patient differences in pain tolerance
- formulation temperature (should ideally be close to body temperature)
- type of injectable device (prefilled syringe or autoinjector)
- injection volume (ideally should be ≤3 mL)
- physiologic pH, and
- excipients.2
As noted in Summary of Injection-Site–Related AEs During Phase 3 Double-Blind Treatment: EVOLVE-1, EVOLVE-2, REGAIN, a similar incidence of injection-site pain was observed during short-term exposure between placebo- and galcanezumab-treated patients. This may explain the possibility that formulation-based factors could have resulted in injection-site pain, including
- a nonphysiological pH of less than 7 (galcanezumab pH is 5.3-6.3), and
- the presence of polysorbate 80.2
Other inactive excipients in the galcanezumab formulation include L-histidine, histidine hydrochloride monohydrate, and sodium chloride.2
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Postmarketing spontaneous reports related to injection-site-related AEs
Through September 27, 2022, Medical Dictionary for Regulatory Activities terms related to injection-site reactions that have been reported in the Eli Lilly and Company spontaneous AE database are provided in Galcanezumab Postmarketing Reporting Rates of Injection-Site Reactions Through 27 September 2022.3
Uncommonly Reported (≥0.1% and <1%) |
Rarely Reported (≥0.01% and <0.1%) |
Very Rarely Reported (<0.01%) |
Injection site erythema, injection site hemorrhage, injection site pain, injection site pruritus, injection site reaction, injection site swelling |
Injection site bruising, injection site discomfort, injection site hypersensitivity, injection site induration, injection site injury, injection site irritation, injection site mass, injection site rash, injection site urticaria, injection site warmth |
Injection site abscess, injection site atrophy, injection site cellulitis, injection site coldness, injection site cyst, injection site dermatitis, injection site discharge, injection site discoloration, injection site dryness, injection site eczema, injection site exfoliation, injection site extravasation, injection site hematoma, injection site hyperesthesia, injection site hypertrophy, injection site hypoesthesia, injection site infection, injection site inflammation, injection site joint erythema, injection site laceration, injection site macule, injection site nodule, injection site edema, injection site pallor, injection site papule, injection site paresthesia, injection site plaque, injection site pustule, injection site scab, injection site scar, injection site streaking, injection site vesicles |
Abbreviation: MedDRA = Medical Dictionary for Regulatory Activities.
aMedDRA preferred terms.
Postmarketing data do not necessarily represent the rate of occurrence of an AE in a treated population, but they represent a reporting rate of a particular AE to the company. Spontaneous reporting of AEs can be highly variable and is not appropriately controlled clinical information on which to base an assessment of whether a particular drug product is the causal agent of an event.14
Spontaneous reporting has limited use due to
- lack of control population
- under-reporting or reporting bias, and
- missing or incomplete information regarding medical history or concomitant medications.14
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References
1Emgality [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.
2Stauffer VL, Wang S, Bonner J, et al. Evaluation of injection-site-related adverse events with galcanezumab: a post hoc analysis of phase 3 studies in participants with migraine. BMC Neurol. 2020;20(1):194. https://doi.org/10.1186/s12883-020-01775-4
3Data on file, Eli Lilly and Company and/or one of its subsidiaries.
4Mulleners WM, Kim BK, Láinez MJA, et al. Safety and efficacy of galcanezumab in patients for whom previous migraine preventive medication from two to four categories had failed (CONQUER): a multicentre, randomised, double-blind, placebo-controlled, phase 3b trial. Lancet Neurol. 2020;19(10):814-825. http://dx.doi.org/10.1016/S1474-4422(20)30279-9
5Bangs ME, Kudrow D, Wang S, et al. Safety and tolerability of monthly galcanezumab injections in patients with migraine: integrated results from migraine clinical studies. BMC Neurol. 2020;20(1):25. https://doi.org/10.1186/s12883-020-1609-7
6Camporeale A, Kudrow D, Sides R, et al. A phase 3, long-term, open-label safety study of galcanezumab in patients with migraine. BMC Neurol. 2018;18(1):188. http://dx.doi.org/10.1186/s12883-018-1193-2
7Stauffer VL, Lanteri-Minet M, García-Azorín D, et al. Characterization of injection-site reactions from the CONQUER study of galcanezumab in patients with treatment-resistant migraine. Cephalalgia. 2020;40(suppl 1):18-110. Migraine Trust Virtual 2020 - Digital Symposium abstract MTV20-DP-053. https://doi.org/10.1177/0333102420962305
8Sakai F, Ozeki A, Skljarevski V. Efficacy and safety of galcanezumab for prevention of migraine headache in Japanese patients with episodic migraine: a phase 2 randomized controlled clinical trial. Cephalalgia Rep. 2020;3:251581632093257. http://dx.doi.org/10.1177/2515816320932573
9Pozo-Rosich P, Detke HC, Wang S, et al. Long-term treatment with galcanezumab in patients with chronic migraine: results from the open-label extension of the REGAIN study. Curr Med Res Opin. 2022;38(5):731-742. https://doi.org/10.1080/03007995.2022.2059975
10Martinez JM, Hindiyeh N, Anglin G, et al. Assessment of immunogenicity from galcanezumab phase 3 trials in patients with episodic or chronic migraine. Cephalalgia. 2020;40(9):978-989. https://doi.org/10.1177/0333102420920642
11Ogston-Tuck S. Subcutaneous injection technique: an evidence-based approach. Nurs Stand. 2014;29(3):53-58. http://dx.doi.org/10.7748/ns.29.3.53.e9183
12Emgality [package insert]. Indianapolis, IN: Eli Lilly and Company; 2021.
13Workman B. Safe injection techniques. Nurs Stand. 1999;13(39):47-53. https://doi.org/10.7748/ns1999.06.13.39.47.c2623
14Goldman SA. Limitations and strengths of spontaneous reports data. Clin Ther. 1998;20(suppl 3):C40-C44. http://dx.doi.org/10.1016/S0149-2918(98)80007-6
15Stauffer VL, Dodick DW, Zhang Q, et al. Evaluation of galcanezumab for the prevention of episodic migraine: the EVOLVE-1 randomized clinical trial. JAMA Neurol. 2018;75(9):1080-1088. http://dx.doi.org/10.1001/jamaneurol.2018.1212
16Skljarevski V, Matharu M, Millen BA, et al. Efficacy and safety of galcanezumab for the prevention of episodic migraine: results of the EVOLVE-2 phase 3 randomized controlled clinical trial. Cephalalgia. 2018;38(8):1442-1454. http://dx.doi.org/10.1177/0333102418779543
17Detke HC, Goadsby PJ, Wang S, et al. Galcanezumab in chronic migraine: the randomized, double-blind, placebo-controlled REGAIN study. Neurology. 2018;91(24):e2211-e2221. http://dx.doi.org/10.1212/WNL.0000000000006640
18Detke HC, Reuter U, Lucas C, et al. Galcanezumab in patients with treatment-resistant migraine: results from the open-label phase of the CONQUER phase 3 trial. Eur J Neurol. 2020;27(suppl 1):298. Congress of the European Academy of Neurology abstract EPR2071. https://doi.org/10.1111/ene.14307
19Stauffer VL, Sides R, Lanteri-Minet M, et al. Comparison between prefilled syringe and autoinjector devices on patient-reported experiences and pharmacokinetics in galcanezumab studies. Patient Prefer Adherence. 2018;12:1785-1795. http://dx.doi.org/10.2147/ppa.s170636
20Reuter U, Lucas C, Dolezil D, et al. Galcanezumab in patients with multiple previous migraine preventive medication category failures: results from the open-label period of the CONQUER trial. Adv Ther. 2021;38:5465-5483. http://dx.doi.org/10.1007/s12325-021-01911-7
Appendix
Evaluation of injection-site–related adverse events in the galcanezumab migraine prevention clinical studies
Injection-site–related AEs were evaluated in phase 3 galcanezumab studies including
- 2 randomized, double-blind, placebo-controlled, 6-month episodic migraine prevention studies (EVOLVE-1 and EVOLVE-2)15,16
- 1 randomized, double-blind, placebo-controlled, 3-month chronic migraine prevention study with an optional 9-month open-label extension phase (REGAIN)17
- 1 randomized, double-blind, placebo-controlled, 3-month migraine prevention study with an optional 3-month open-label extension phase in patients with episodic or chronic migraine who had not benefited from multiple previous migraine preventive treatments (CONQUER), and4,18
- a 12-month, open-label safety study in patients with episodic or chronic migraine (CGAJ).6
The recommended dose of galcanezumab is 120 mg galcanezumab injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose.1 The results of a maintenance dose of galcanezumab 240 mg once monthly are also described here. Even though this dose has been tested in pivotal studies, it has not been approved and therefore is not recommended.
In addition, injection-site–related AEs from a phase 2, double-blind, placebo-controlled, 6-month study in Japanese patients with episodic migraine (study CGAN) are also summarized.8
The long-term analysis set discussed below includes galcanezumab-treated patients from the
- double-blind and open-label extension phase of REGAIN (month 0-12), and
- 12-month open-label safety study, CGAJ.2
There were differences in the device and who administered the injections between EVOLVE-1, EVOLVE-2, REGAIN, CONQUER, CGAJ, and study CGAN as shown in Device and Injection Administration in Galcanezumab Migraine Prevention Studies.
In study... |
Patients received... |
SQ injectionsa were administered... |
With a volume of... |
By... |
Using the following device... |
2 SQ injectionsb |
monthly |
1 mLc |
investigative site personnel |
prefilled syringe |
|
1 or 2 SQ injectionsd |
monthly |
1 mLc |
self-administratione |
prefilled syringe or autoinjectorf |
|
1 or 2 SQ injectionsg |
monthly |
1 mLc |
investigative site personnel |
prefilled syringe |
|
1 or 2 SQ injectionsh |
monthly |
1 mLc |
investigative site personnel |
prefilled syringe |
Abbreviation: SQ = subcutaneous.
aPossible injection sites included the abdomen, thigh, upper arm, or buttocks.
bEVOLVE-1, EVOLVE-2, REGAIN, and CGAN: patients received 2 injections of 1 mL each via SQ injection at each visit. Patients received either galcanezumab 120 mg (2 injections of galcanezumab 120 mg as loading dose at first dosing visit, followed by 1 injection each of galcanezumab 120 mg and placebo at all subsequent dosing visits), galcanezumab 240 mg (2 injections of galcanezumab 120 mg), or placebo (2 placebo injections).
cEach injection was 1 mL.
dCGAJ: Patients randomized to the galcanezumab 120-mg dose received an initial loading dose of 240 mg (2 SQ injections of 120 mg each; 1 mL each) and 1 injection of 120 mg at each subsequent dosing visit. Patients randomized to the galcanezumab 240-mg dose received 2 SQ injections of 120 mg at each dosing visit.
eInvestigative site personnel administered the first injection. Self/caregiver administration started at the second injection visit after the loading dose administration by site staff and review of instructions for use for self-administration.
fPatients were switched from the prefilled syringe device to the autoinjector device. The device switch started after all patients had completed at least month 9 of the study, and 179 patients in study CGAJ received ≥1 galcanezumab dose using the autoinjector. Patients had up to 3-months exposure with the autoinjector.
gCONQUER: At the beginning of double-blind treatment, patients received either galcanezumab 120 mg (2 injections of galcanezumab 120 mg as loading dose at first dosing visit, followed by 1 injection of galcanezumab 120 mg at all subsequent dosing visits), or placebo (2 placebo injections at the first dosing visit, followed by 1 injection of placebo at subsequent dosing visits). At the beginning of open-label treatment, all patients received 2 injections to allow for blinded 240-mg loading dose of galcanezumab at month 3. Specifically, patients randomized to placebo during double-blind treatment received a loading dose of galcanezumab 240 mg, and patients randomized to galcanezumab during double-blind treatment received 1 injection of galcanezumab 120 mg and 1 injection of placebo.
hEVOLVE-1, EVOLVE-2, REGAIN, and CGAN: patients received 2 injections of 1 mL each via SQ injection at each visit. Patients received either galcanezumab 120 mg (2 injections of galcanezumab 120 mg as loading dose at first dosing visit, followed by 1 injection each of galcanezumab 120 mg and placebo at all subsequent dosing visits), galcanezumab 240 mg (2 injections of galcanezumab 120 mg), or placebo (2 placebo injections).
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Summary of injection site-related adverse events in galcanezumab migraine prevention clinical studies
PBO |
GMB 120 mg |
GMB 240 mg |
GMB Pooled |
|
Patients with ≥1 TEAE |
183 (12.6) |
128 (18.2)d |
294 (20.5)d |
|
Patients with ≥1 TEAE, excluding injection site painf |
60 (4.1) |
70 (9.9)d |
176 (12.3)d |
|
Injection site pain |
138 (9.5) |
71 (10.1) |
85 (11.6) |
156 (10.9) |
Unspecified injection site reaction |
14 (1.0) |
22 (3.1)d |
67 (4.7)d |
|
Injection site erythema |
20 (1.4) |
20 (2.8)i |
29 (4.0)d |
49 (3.4)d |
Injection site pruritus |
2 (0.1) |
15 (2.1)d |
24 (3.3)d |
39 (2.7)d |
Injection site bruising |
9 (0.6) |
4 (0.6) |
10 (1.4) |
14 (1.0) |
Injection site swelling |
1 (0.1) |
8 (1.1)d |
4 (0.6)j |
12 (0.8)k |
Injection site rash |
2 (0.1) |
6 (0.9)l |
4 (0.6) |
10 (0.7)m |
Injection site induration |
1 (0.1) |
3 (0.4) |
3 (0.4) |
6 (0.4) |
Injection site discomfort |
3 (0.2) |
3 (0.4) |
2 (0.3) |
5 (0.4) |
Injection site hematoma |
7 (0.5) |
1 (0.1) |
3 (0.4) |
4 (0.3) |
Injection site hypersensitivity |
0 (0.0) |
1 (0.1) |
3 (0.4)n |
4 (0.3)o |
Injection site mass |
0 (0.0) |
3 (0.4)p |
0 (0.0) |
3 (0.2) |
Injection site hemorrhage |
2 (0.1) |
1 (0.1) |
1 (0.1) |
2 (0.1) |
Injection site inflammation |
0 (0.0) |
1 (0.1) |
1 (0.1) |
2 (0.1) |
Injection site irritation |
3 (0.2) |
1 (0.1) |
1 (0.1) |
2 (0.1) |
Injection site urticaria |
1 (0.1) |
1 (0.1) |
1 (0.1) |
2 (0.1) |
Injection site discoloration |
0 (0.0) |
0 (0.0) |
1 (0.1) |
1 (0.1) |
Injection site edema |
1 (0.1) |
1 (0.1) |
0 (0.0) |
1 (0.1) |
Injection site papule |
0 (0.0) |
1 (0.1) |
0 (0.0) |
1 (0.1) |
Injection site vesicles |
0 (0.0) |
0 (0.0) |
1 (0.1) |
1 (0.1) |
Injection site warmth |
1 (0.1) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
Abbreviations: AE = adverse event; GMB = galcanezumab; MedDRA = Medical Dictionary for Regulatory Activities; PBO = placebo; TEAE = treatment-emergent adverse event.
aPrefilled syringe was used in these trials.
bPreferred term.
cAll AEs listed in the MedDRA version 19.1 high-level term of "injection-site reactions" were analyzed.
dp<.001 vs PBO.
ep=.033 vs GMB 120 mg.
fMost frequently reported terms (not less than 1.5% of all preferred terms which included: injection-site reaction, injection-site erythema, and injection-site pruritus).
gp=.008 vs GMB 120 mg.
hp=.006 vs GMB 120 mg.
ip=.017 vs PBO.
jp=.028 vs PBO.
kp=.002 vs PBO.
lp=.011 vs PBO.
mp=.02 vs PBO.
np=.015 vs PBO.
op=.044 vs PBO.
pp=.012 vs PBO.
|
PBO |
GMB 120 mg |
GMB 120 mg |
Double-Blind Treatment Phase |
Open-Label Treatment Phased |
||
Patients with ≥1 TEAE |
23.0 (10.0) |
16 (6.9) |
50 (10.9) |
Injection-site erythema |
6 (2.6) |
8 (3.5) |
19 (4.2) |
Injection-site pain |
13 (5.7) |
5 (2.2) |
20 (4.4) |
Injection-site pruritus |
0 (0.0) |
3 (1.3) |
9 (2.0) |
Injection-site edema |
0 (0.0) |
2 (0.9) |
3 (0.7) |
Injection-site discoloration |
1 (0.4) |
1 (0.4) |
3 (0.7) |
Injection-site hypersensitivity |
0 (0.0) |
1 (0.4) |
1 (0.2) |
Injection-site induration |
4 (1.7) |
1 (0.4) |
5 (1.1) |
Injection-site paresthesia |
3 (1.3) |
1 (0.4) |
3 (0.7) |
Injection-site swelling |
0 (0.0) |
1 (0.4) |
2 (0.4) |
Injection-site bruising |
4 (1.7) |
0 (0.0) |
2 (0.4) |
Injection-site hematoma |
1 (0.4) |
0 (0.0) |
1 (0.2) |
Injection-site reaction |
6 (2.6)e |
0 (0.0) |
8 (1.8) |
Injection-site inflammation |
NR |
NR |
1 (0.2) |
Injection-site irritation |
NR |
NR |
1 (0.2) |
Injection-site rash |
NR |
NR |
1 (0.2) |
Injection-site vesicles |
NR |
NR |
1 (0.2) |
Injection-site warmth |
NR |
NR |
1 (0.2) |
Abbreviations: AE = adverse event; GMB = galcanezumab; MedDRA = Medical Dictionary for Regulatory Activities; NR = not reported; PBO = placebo; TEAE = treatment-emergent adverse event.
aPrefilled syringe was used in this study.
bPreferred term.
cAdverse events related to injection-sites were defined using terms from the MedDRA version 22.0 high level-term of "Injection site reactions".
dGalcanezumab-treated population: patients who received up to 6 months of GMB treatment in addition to patients on PBO in the double-blind treatment phase who received GMB during open-label treatment.
ep=.015 vs GMB 120 mg.
PBO |
GMB 120 mg |
GMB 240 mg |
GMB Pooled |
|
Patients with ≥1 TEAE |
13 (5.7) |
30 (26.1)d |
75 (32.8)d |
|
Patients with ≥1 TEAE, excluding injection-site pain |
12 (5.2) |
27 (23.5)d |
70 (30.6)d |
|
Injection-site erythema |
5 (2.2) |
17 (14.8)d |
48 (21.0)d |
|
Injection-site pruritus |
0 (0.0) |
10 (8.7)d |
33 (14.4)d |
|
Injection-site swelling |
3 (1.3) |
12 (10.4)d |
12 (10.5)d |
24 (10.5)d |
Injection-site pain |
3 (1.3) |
7 (6.1)i |
8 (7.0)j |
15 (6.6)k |
Injection-site induration |
1 (0.4) |
3 (2.6) |
3 (2.6) |
6 (2.6) |
Injection-site inflammation |
0 (0.0) |
3 (2.6)l |
0 (0.0) |
3 (1.3) |
Injection-site rash |
2 (0.9) |
0 (0.0) |
3 (2.6) |
3 (1.3) |
Injection-site warmth |
0 (0.0) |
2 (1.7) |
1 (0.9) |
3 (1.3) |
Injection-site bruising |
4 (1.7) |
2 (1.7) |
0 (0.0) |
2 (0.9) |
Injection-site mass |
0 (0.0) |
1 (0.9) |
1 (0.9) |
2 (0.9) |
Injection-site urticaria |
0 (0.0) |
1 (0.9) |
1 (0.9) |
2 (0.9) |
Injection-site dermatitis |
0 (0.0) |
0 (0.0) |
1 (0.9) |
1 (0.4) |
Injection-site eczema |
0 (0.0) |
0 (0.0) |
1 (0.9) |
1 (0.4) |
Injection-site hemorrhage |
1 (0.4) |
1 (0.9) |
0 (0.0) |
1 (0.4) |
Injection-site discoloration |
1 (0.4) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
Injection-site discomfort |
1 (0.4) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
Injection-site reaction |
1 (0.4) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
Abbreviations: AE = adverse event; GMB = galcanezumab; MedDRA = Medical Dictionary for Regulatory Activities; PBO = placebo; TEAE = treatment-emergent adverse event.
aPrefilled syringe was used in this study.
bPreferred term.
cAdverse events related to injection-sites were defined using terms from the MedDRA version 21.1 high-level term of "Injection site reactions".
dp<.001 vs PBO.
ep=.035 vs GMB 120 mg.
fp=.022 vs GMB 120 mg.
gp=.024 vs GMB 120 mg.
hp=.015 vs GMB 120 mg.
ip=.018 vs PBO.
jp=.008 vs PBO.
kp=.004 vs PBO.
lp=.036 vs PBO.
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▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.
Date of Last Review: 03 August 2023