A Study of Galcanezumab in Participants With Chronic Cluster Headache

Chronic Cluster Headache Clinical Trial

Official title:

A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study of : Galcanezumab (LY2951742) With a Long-Term Open-Label Extension in Patients With Chronic Cluster Headache

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02438826
• Other study ID #: 15781
• Secondary ID: I5Q-MC-CGAM2014-
• Status: Completed
• Phase: Phase 3
• Start date: June 18, 2015
• Est. completion date: August 14, 2019

Study information

• Verified date: June 2020
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study is to evaluate the efficacy of the study drug known as galcanezumab in participants with chronic cluster headache.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 240
• Est. completion date: August 14, 2019
• Est. primary completion date: March 27, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Participants with a history of chronic cluster headache occurring without a remission period, or with remissions lasting <1 month, for at least 1 year.

• Participants are able to distinguish cluster headache attacks from other headaches.

Exclusion Criteria:

• Current enrollment in or discontinuation within the last 30 days from, a clinical trial involving any investigational drug or device.

• Current use or any prior exposure to any calcitonin-gene-related peptide (CGRP) antibody, any antibody to the CGRP receptor, or antibody to nerve growth factor (NGF).

• Are taking indomethacin and/or are suspected of having another distinct trigeminal autonomic cephalalgia.

• A history of migraine variants that could implicate or could be confused with ischemia.

• Known hypersensitivity to multiple drugs, monoclonal antibodies or other therapeutic proteins.

• A history or presence of other medical illness that indicates a medical problem that would preclude study participation.

• Evidence of significant active or unstable psychiatric disease, in the opinion of the investigator.

• Women who are pregnant or nursing.

Related Conditions & MeSH terms

• Chronic Cluster Headache
• Cluster Headache
• Headache

Intervention

Drug:
• Galcanezumab 300 mg
Administered SC
• Placebo
Administered SC

Locations

Country	Name	City	State
Belgium	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Gent
Belgium	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Liege
Canada	For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.	Montreal
Canada	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Montréal
Canada	For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.	Toronto
Denmark	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Glostrup
Denmark	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Glostrup
Finland	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Helsinki
Finland	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Turku
France	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Lille
France	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Marseille
France	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Nice
France	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Paris
France	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Paris
France	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Saint Etienne Cedex 2
Germany	Praxis Dr. Stude	Bochum
Germany	Universtitätsklinikum Essen AöR	Essen
Germany	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Hamburg
Germany	For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.	Jena
Germany	Migräne- und Kopfschmerzklinik GmbH & Co. KG	Königstein
Germany	Klinikum der Universität München Campus Großhadern	München
Greece	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Athens
Greece	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Athens
Italy	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Firenze
Italy	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Milano
Italy	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Pavia
Netherlands	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Amsterdam
Netherlands	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Nijmegen
Spain	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Barcelona
Spain	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Valencia
United Kingdom	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Hull
United Kingdom	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Liverpool
United Kingdom	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	London
United Kingdom	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Stoke-on-Trent
United States	Michigan Head, Pain and Neurological Institute	Ann Arbor	Michigan
United States	Northwest Clinical Research Center	Bellevue	Washington
United States	Southwestern Medical Center - Dallas	Dallas	Texas
United States	Colorado Neurological Institute	Englewood	Colorado
United States	Mayo Clinic-Jacksonville	Jacksonville	Florida
United States	West Virginia University Hospital	Morgantown	West Virginia
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Mayo Clinic Hospital	Phoenix	Arizona
United States	California Medical Clinic for Headache	Santa Monica	California
United States	New England Institute for Clinical Research	Stamford	Connecticut
United States	Stanford University Hospital	Stanford	California
United States	Tampa General Hospital	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Denmark,  Finland,  France,  Germany,  Greece,  Italy,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Mean Change From Baseline in Weekly Cluster Headache Attack Frequency	Number of cluster headache attacks was recorded daily by study participants in their ePRO Diary, Baseline and 12 weeks of daily data during double-blind treatment phase will be converted into 14-calendar day intervals: the baseline 14-day interval, Weeks 1/2, 3/4, 5/6, 7/8, 9/10, and 11/12. Next, the biweekly interval results were adjusted to 7-day (weekly) interval in order to report the outcome as weekly frequency. Overall mean change from baseline is derived from mixed model repeated measures (MMRM) analysis. Least Square (LS) means were calculated using MMRM model with treatment, sex, verapamil use, pooled investigative site, week, baseline, and treatment by week as fixed effects.	Baseline, Week 1 through Week 12
Secondary	Percentage of Participants With a 50% or Greater Reduction From Baseline in the Weekly Number of Cluster Headache Attacks	A 50% responder is any participant who has a =50% reduction from baseline in the weekly number of cluster headache attacks in a 14-day interval: Weeks 1/2, Weeks 3/4, Weeks 5/6, Weeks 7/8, Weeks 9/10, and Weeks 11/12. Mean percentage of participants is derived from the average of weeks 1/2 to weeks 11/12 from generalized linear mixed model repeated measures method with treatment, sex, verapamil use, week, treatment by week, and baseline as fixed effects.	Baseline, Week 1 through Week 12
Secondary	Percentage of Participants With a Sustained Response of 50% or Greater Reduction From Baseline in the Weekly Number of Cluster Headache Attacks	Sustained Response is defined as a 50% or greater reduction in the weekly cluster attack frequency from baseline to Weeks 3/4 and maintained at Weeks 5/6, Weeks 7/8, Weeks 9/10, and Weeks 11/12. Percentage of participants with a sustained response was analyzed using Koch's nonparametric randomization-based analysis of covariance method. This method adjusted for pooled investigative site by including it as a stratification variable. It also adjusted for sex, verapamil use and baseline value.	Baseline, Week 3 through Week 12
Secondary	Percentage of Participants With a 30% Reduction in the Weekly Number of Cluster Headache Attacks	A 30% responder is any participant who has a =30% reduction from baseline in the weekly number of cluster headache attacks in a 14-day interval. Weeks 1/2, 3/4, 5/6, 7/8, 9/10, and 11/12. Mean percentage of participants is derived from the average of weeks 1/2 to weeks 11/12 from generalized linear mixed model repeated measures method with treatment, sex, verapamil use, week, treatment by week, and baseline as fixed effects. .	Baseline, Week 1 through Week 12
Secondary	Percentage of Participants Reporting a Score of 1 or 2 on the Patient Global Impression of Improvement (PGI-I)	PGI-I requests participants to mark the box that best describes their cluster headache condition since they started taking the medicine. The options in the displayed boxes are represented on a 7-point scale, with 1 = very much better, 2 = much better, 3 = a little better, 4 = no change, 5 = a little worse, 6 = much worse, and 7 = very much worse. Percentage of participants were derived with a generalized linear mixed model repeated measures method with treatment, sex, verapamil use, baseline cluster headache attack category, month, and treatment by month as fixed effects.	Week 4
Secondary	Percentage of Participants Reporting a Score of 1 or 2 on the Patient Global Impression of Improvement (PGI-I)	PGI-I requests participants to mark the box that best describes their cluster headache condition since they started taking the medicine. The options in the displayed boxes are represented on a 7-point scale, with 1 = very much better, 2 = much better, 3 = a little better, 4 = no change, 5 = a little worse, 6 = much worse, and 7 = very much worse. Percentage of participants were derived with a generalized linear mixed model repeated measures method with treatment, sex, verapamil use, baseline cluster headache attack category, month, and treatment by month as fixed effects.	Week 8
Secondary	Percentage of Participants Reporting a Score of 1 or 2 on the Patient Global Impression of Improvement (PGI-I)	PGI-I requests participants to mark the box that best describes their cluster headache condition since they started taking the medicine. The options in the displayed boxes are represented on a 7-point scale, with 1 = very much better, 2 = much better, 3 = a little better, 4 = no change, 5 = a little worse, 6 = much worse, and 7 = very much worse. Percentage of participants were derived with a generalized linear mixed model repeated measures method with treatment, sex, verapamil use, baseline cluster headache attack category, month, and treatment by month as fixed effects.	Week 12
Secondary	Percentage of Participants With Suicidal Ideation Assessed by Columbia - Suicide Severity Rating Scale (C-SSRS)	C-SSRS captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. The scale includes suggested questions to solicit the type of information needed to determine if a suicide-related thought or behavior occurred. Some questions are binary responses (yes/no) and some are on a scale of 1 (low severity) to 5 (high severity). Suicidal ideation: a "yes" answer to any of 5 suicidal ideation questions: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods without intent to act, active suicidal ideation with some intent to act without specific plan, active suicidal ideation with specific plan and intent.	Week 1 through Week 12
Secondary	Percentage of Participants With Suicidal Behaviors Assessed by Columbia - Suicide Severity Rating Scale (C-SSRS)	C-SSRS captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. The scale includes suggested questions to solicit the type of information needed to determine if a suicide-related thought or behavior occurred. Some questions are binary responses (yes/no) and some are on a scale of 1 (low severity) to 5 (high severity). Suicidal behavior: a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide.	Week 1 through Week 12
Secondary	Percentage of Participants Developing Anti-Drug Antibodies (ADA) to Galcanezumab (LY2951742)	Treatment emergent (TE) ADA evaluable participant is considered to be TE ADA+ if the subject has at least one post-baseline titer that is a 4-fold or greater increase in titer from baseline measurement. If baseline result is ADA Not Present, then the participant is TE ADA+ if there is at least one post-baseline result of ADA present with titer >= 1: 20.	Baseline, Week 1 through Week 12
Secondary	Pharmacokinetics (PK): Serum Concentration of Galcanezumab	Pharmacokinetics (PK): Serum Concentration of Galcanezumab	Week 2
Secondary	Pharmacokinetics (PK): Serum Concentration of Galcanezumab	Pharmacokinetics (PK): Serum Concentration of Galcanezumab	Week 4
Secondary	Pharmacokinetics (PK): Serum Concentration of Galcanezumab	Pharmacokinetics (PK): Serum Concentration of Galcanezumab	Week 8
Secondary	Pharmacokinetics (PK): Serum Concentration of Galcanezumab	Pharmacokinetics (PK): Serum Concentration of Galcanezumab	Week 12

External Links

•   Click here for more information about this study: A Study of LY2951742 in Participants With Chronic Cluster Headache