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Research article
Evaluation of injection-site-related adverse events with galcanezumab: a post hoc analysis of Phase 3 studies in participants with migraine
Virginia L. Stauffer
Eli Lilly and Co
Corresponding Author
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Background: Injection-site reactions have been reported with biologicals. In this post hoc analysis of Phase 3 studies in participants with migraine, we provide a comprehensive overview and detailed summary of injection-site reaction with galcanezumab.
Methods: Data were obtained from two randomised clinical studies in participants with episodic migraine (EVOLVE-1 and EVOLVE-2), one randomised study in participants with chronic migraine (REGAIN) and one open-label study (Study CGAJ) in participants with episodic or chronic migraine. The injection-site reactions were measured for two different cohorts: 1) six-month double-blind treatment phase in the EVOLVE-1 and EVOLVE-2 studies and three-month double-blind treatment phase in the REGAIN study, where participants received placebo and galcanezumab (placebo-controlled analysis set); 2) three month double-blind (Month 0 to Month 3; 1:1:placebo:galcanezumab) + nine months open-label extension phase (Month 3 to Month 12) of REGAIN and twelve month open-label phase of Study CGAJ, where participants received only galcanezumab (galcanezumab exposure analysis set).
Results: A total of 477 participants in the placebo-controlled analysis set (galcanezumab 240 mg, 166/730 [22.7%]; galcanezumab 120 mg, 128/705 [18.2%]; placebo, 183/1451 [12.6%]) reported at least one injection-site reaction. Most of the injection-site reactions were reported as injection-site pain, unspecified injection-site reaction, injection-site erythema, and injection-site pruritus. The incidence of injection-site pain was highest among all reported Injection-site reactions and were reported with similar frequency by participants receiving galcanezumab (galcanezumab 120mg, 10.1%; galcanezumab 240 mg, 11.6%) and placebo (9.5%) and was the most common injection-site reaction reported within 60 minutes of injection (~86% of participants). The frequency of unspecified injection-site reaction, injection-site erythema and injection-site pruritus was significantly (P<0.001) higher in participant receiving galcanezumab versus placebo. In the galcanezumab exposure analysis set participants received up to 12 doses and the frequency of injection-site reactions reported for both doses combined was 21.8%. The reporting of injection-site reactions did not increase with the number of doses received. No ISR-related serious adverse events were reported in both the placebo-controlled and galcanezumab exposure analysis sets.
Conclusions: The most common adverse event of galcanezumab is injection-site reactions. However, these events were generally mild-to-moderate in severity, non-serious, resolved spontaneously, and discontinuations due to injection-site reactions were low (1%).
Keywords
Injection-site reaction, monoclonal antibody, migraine, physiological, formulation factors.
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CURRENT STATUS: Under Review
Version 2
Posted 13 May, 2020
No community comments so far
Editorial decision: Minor revision
On 06 May, 2020
Editor assigned
On 29 Apr, 2020
Editor invited
On 28 Apr, 2020
Submission checks complete
On 20 Feb, 2020
No comments provided
Editorial decision: Minor revision
On 12 Apr, 2020
Review #3 received
Received 11 Apr, 2020
Review #2 received
Received 09 Apr, 2020
Reviewer #3 agreed
On 30 Mar, 2020
Review #1 received
Received 24 Feb, 2020
Reviewer #2 agreed
On 24 Feb, 2020
Reviewer #1 agreed
On 23 Feb, 2020
Reviewers invited
Invitations sent on 21 Feb, 2020
Editor assigned
On 18 Feb, 2020
Submission checks complete
On 17 Feb, 2020
Editor invited
On 17 Feb, 2020
First submitted
On 15 Feb, 2020
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This preprint is under consideration at BMC Neurology. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Evaluation of injection-site-related adverse events with galcanezumab: a post hoc analysis of Phase 3 studies in participants with migraine
Virginia L. Stauffer
Eli Lilly and Co
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 2
Posted 13 May, 2020
No community comments so far
Editorial decision: Minor revision
On 06 May, 2020
Editor assigned
On 29 Apr, 2020
Editor invited
On 28 Apr, 2020
Submission checks complete
On 20 Feb, 2020
No comments provided
Editorial decision: Minor revision
On 12 Apr, 2020
Review #3 received
Received 11 Apr, 2020
Review #2 received
Received 09 Apr, 2020
Reviewer #3 agreed
On 30 Mar, 2020
Review #1 received
Received 24 Feb, 2020
Reviewer #2 agreed
On 24 Feb, 2020
Reviewer #1 agreed
On 23 Feb, 2020
Reviewers invited
Invitations sent on 21 Feb, 2020
Editor assigned
On 18 Feb, 2020
Submission checks complete
On 17 Feb, 2020
Editor invited
On 17 Feb, 2020
First submitted
On 15 Feb, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Injection-site reactions have been reported with biologicals. In this post hoc analysis of Phase 3 studies in participants with migraine, we provide a comprehensive overview and detailed summary of injection-site reaction with galcanezumab.
Methods: Data were obtained from two randomised clinical studies in participants with episodic migraine (EVOLVE-1 and EVOLVE-2), one randomised study in participants with chronic migraine (REGAIN) and one open-label study (Study CGAJ) in participants with episodic or chronic migraine. The injection-site reactions were measured for two different cohorts: 1) six-month double-blind treatment phase in the EVOLVE-1 and EVOLVE-2 studies and three-month double-blind treatment phase in the REGAIN study, where participants received placebo and galcanezumab (placebo-controlled analysis set); 2) three month double-blind (Month 0 to Month 3; 1:1:placebo:galcanezumab) + nine months open-label extension phase (Month 3 to Month 12) of REGAIN and twelve month open-label phase of Study CGAJ, where participants received only galcanezumab (galcanezumab exposure analysis set).
Results: A total of 477 participants in the placebo-controlled analysis set (galcanezumab 240 mg, 166/730 [22.7%]; galcanezumab 120 mg, 128/705 [18.2%]; placebo, 183/1451 [12.6%]) reported at least one injection-site reaction. Most of the injection-site reactions were reported as injection-site pain, unspecified injection-site reaction, injection-site erythema, and injection-site pruritus. The incidence of injection-site pain was highest among all reported Injection-site reactions and were reported with similar frequency by participants receiving galcanezumab (galcanezumab 120mg, 10.1%; galcanezumab 240 mg, 11.6%) and placebo (9.5%) and was the most common injection-site reaction reported within 60 minutes of injection (~86% of participants). The frequency of unspecified injection-site reaction, injection-site erythema and injection-site pruritus was significantly (P<0.001) higher in participant receiving galcanezumab versus placebo. In the galcanezumab exposure analysis set participants received up to 12 doses and the frequency of injection-site reactions reported for both doses combined was 21.8%. The reporting of injection-site reactions did not increase with the number of doses received. No ISR-related serious adverse events were reported in both the placebo-controlled and galcanezumab exposure analysis sets.
Conclusions: The most common adverse event of galcanezumab is injection-site reactions. However, these events were generally mild-to-moderate in severity, non-serious, resolved spontaneously, and discontinuations due to injection-site reactions were low (1%).