A Placebo-Controlled Study of Galcanezumab in Patients with Episodic Cluster Headache: Results from the 8-Week Double-Blind Treatment Phase (Plen02.004)

Objective: To assess the efficacy and safety of galcanezumab in individuals with episodic cluster headache (CH). Background: Patients with episodic CH experience recurrent intense, unilateral headache “attacks” with cranial autonomic symptoms and/or restlessness. Efficacious treatments that reduce attack frequency remain an unmet need. Design/Methods: This study comprised four periods: screening; prospective baseline; 8-week, double-blind, placebo-controlled treatment; and washout. We present results from the double-blind treatment period. Participants were randomized 1:1 to galcanezumab 300 mg (N=49) or placebo (N=57) subcutaneously (SC) once monthly. The primary endpoint was overall mean change from baseline in weekly CH attack frequency across Weeks 1–3. The key secondary endpoint was the proportion of participants achieving a reduction from baseline of ≥50% in weekly CH attack frequency at Week 3. Results: The mean change in weekly CH attack frequency across Weeks 1–3 was −8.7 for galcanezumab versus −5.2 for placebo (treatment groups difference in mean change, −3.5 [95% CI −6.7, −0.2]; p=0.036). The percentage of participants achieving ≥50% reduction in weekly CH attack frequency at Week 3 was 76% for galcanezumab versus 57% for placebo (p=0.04). Four participants (8%) in the galcanezumab group discontinued during the double-blind period versus 12 (21%) in placebo. In the placebo group, 8 (14%) discontinued due to lack of efficacy versus 1 (2%) with galcanezumab (p=0.036). There were no clinically meaningful differences between treatment groups on tolerability or safety parameters except for a greater incidence of injection site pain with galcanezumab versus placebo (8.2% vs 0%, p=0.043). Conclusions: Galcanezumab reduced the weekly CH attack frequency across Weeks 1–3 and resulted in a greater percentage achieving a ≥50% reduction in the weekly CH attack frequency at Week 3. The safety profile of galcanezumab in this population was similar to that seen previously in patients with episodic or chronic migraine. Disclosure: Dr. Bardos has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eli Lilly and Company. Dr. Bardos holds stock and/or stock options in Eli Lilly and Company. Dr. Goadsby has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Amgen Eli-Lilly and Company, Alder Biopharmaceuticals, Allergan, Autonomic Technologies Inc., Dr Reddy’s Laboratories, Electrocore LLC, eNeura, Novartis, Scion, Teva Pharmaceuticals, and Trigemina Inc. Dr. Goadsby has received personal compensation in an editorial capacity for Journal Watch- Massachusetts Medical Society. Dr. Goadsby has received research support from Amgen and Eli-Lilly and Company. Dr. Dodick has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Dr. Dodick reports personal fees from Acorda, Amgen, Alder, Allergan, Autonomic Technologies, Biohaven, Colucid, Eli Lilly, eNeura, Foresight Capital, Neurolief, Zosano, WL Gore, Vedanta Associates, Promius Pharma, Magellan Healthcare, CC West Ford Group, Nocira, Novartis, NuPathe, Supernus, Electrocore, Tonix, Teva, Alcobra, Insys, Ipsen, Charleston Laboratories, Biocentric, Theranica, Xenon. ZP Opco. Travel expense reimbursement and speaking fee from Sun Pharma. Anticipated income from consulting within next 3 weeks not previously reported: Impel pharmaceuticals (currently under review by Mayo Clinic Medical Industry Relations Committee). Compensation for activities related to data safety monitoring committee from Axsome. Speaking fees, or fees related to CME content development: Healthlogix, Medicom Worldwide, Medlogix Communications, MedNet, Miller Medical Communications, PeerView Operation Services America, Web MD/Medscape, American Academy of Neurology, American Headache Society, PeerView Institute for Medical Education, Chameleon Communications, Academy for Continued Healthcare Learning, Universal Meeting Management, Haymarket Medical Education, Global Scientific Communications, UpToDate, Meeting LogiX. Consulting use agreement through employer: NeuroAssessment Systems, Myndshft. Dr. Dodick has received compensation for serving on the Board of Directors of Board of Directors position: King-Devick Technologies, Ontologics. Dr. Dodick holds stock and/or stock options in Hold equity in: Aural Analytics, Healint, Theranica, Second Opinion/Mobile Health, Epien, which sponsored research in which Dr. Dodick was involved as an investigator. Dr. Dodick holds stock and/or stock options in Hold equity in: Aural Analytics, Healint, Theranica, Second Opinion/Mobile Health, and Epien. Dr. Leone has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eli Lilly and TEVA.. Dr. Oakes has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eli Lilly and Company. Dr. Oakes holds stock and/or stock options in Eli Lilly. Dr. Martinez has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eli Lilly and Company. Dr. Martinez holds stock and/or stock options in Eli Lilly and Company which sponsored research in which Dr. Martinez was involved as an investigator. Dr. Martinez holds stock and/or stock options in Eli Lilly and Company. Dr. Millen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eli Lilly and Company. Dr. Zhou has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Eli Lilly and Company. Dr. Zhou holds stock and/or stock options in Eli Lilly and Company. Dr. Dowsett has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eli Lilly and Company. Dr. Aurora has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eli Lilly and Company. Dr. Yang has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eli Lilly and Company. Dr. Conley has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eli Lilly and Company. Dr. Conley holds stock and/or stock options in Eli Lilly and Company, which sponsored research in which Dr. Conley was involved as an investigator. Dr. Conley holds stock and/or stock options in Eli Lilly and Company.