Last reviewed · How we verify

NCT02438826

A Study of Galcanezumab in Participants With Chronic Cluster Headache

Completed Phase 3 Results posted Last updated 25 August 2020
What this trial tests

Phase 3 trial testing Galcanezumab 300 mg in Chronic Cluster Headache in 240 participants. Completed in 14 August 2019.

Timeline
18 June 2015
Primary endpoint
27 March 2018
14 August 2019

Quick facts

Lead sponsorEli Lilly and Company
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment240
Start date18 June 2015
Primary completion27 March 2018
Estimated completion14 August 2019
Sites48 locations across Denmark, France, Finland, Italy, Greece, Netherlands, Belgium, United Kingdom

Drugs / interventions tested

Conditions studied

Sponsor

Eli Lilly and Company — full company profile →

Who can join

Adults 18 to 65, any sex, with Chronic Cluster Headache. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Overall Mean Change From Baseline in Weekly Cluster Headache Attack Frequency Primary · Baseline, Week 1 through Week 12

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, vera

GroupValue95% CI
Placebo-4.59± 0.79
Galcanezumab 300 mg-5.38± 0.81
Percentage of Participants With a 50% or Greater Reduction From Baseline in the Weekly Number of Cluster Headache Attacks Secondary · Baseline, Week 1 through Week 12

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.

GroupValue95% CI
Placebo27.1± 3.5
Galcanezumab 300 mg32.6± 3.8
Percentage of Participants With a Sustained Response of 50% or Greater Reduction From Baseline in the Weekly Number of Cluster Headache Attacks Secondary · Baseline, Week 3 through Week 12

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.

GroupValue95% CI
Placebo17.50
Galcanezumab 300 mg16.24
Percentage of Participants With a 30% Reduction in the Weekly Number of Cluster Headache Attacks Secondary · Baseline, Week 1 through Week 12

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. .

GroupValue95% CI
Placebo39.0± 3.9
Galcanezumab 300 mg49.1± 4.1
Percentage of Participants Reporting a Score of 1 or 2 on the Patient Global Impression of Improvement (PGI-I) Secondary · Week 4

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.

GroupValue95% CI
Placebo19.4
Galcanezumab 300 mg21.5
Percentage of Participants Reporting a Score of 1 or 2 on the Patient Global Impression of Improvement (PGI-I) Secondary · Week 8

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.

GroupValue95% CI
Placebo32.0
Galcanezumab 300 mg32.1
Percentage of Participants Reporting a Score of 1 or 2 on the Patient Global Impression of Improvement (PGI-I) Secondary · Week 12

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.

GroupValue95% CI
Placebo35.6
Galcanezumab 300 mg30.4
Percentage of Participants With Suicidal Ideation Assessed by Columbia - Suicide Severity Rating Scale (C-SSRS) Secondary · Week 1 through Week 12

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 idea

GroupValue95% CI
Placebo5.04
Galcanezumab 300 mg4.31
Percentage of Participants With Suicidal Behaviors Assessed by Columbia - Suicide Severity Rating Scale (C-SSRS) Secondary · Week 1 through Week 12

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.

GroupValue95% CI
Placebo0
Galcanezumab 300 mg0
Percentage of Participants Developing Anti-Drug Antibodies (ADA) to Galcanezumab (LY2951742) Secondary · Baseline, Week 1 through Week 12

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.

GroupValue95% CI
Placebo0
Galcanezumab 300 mg0.88
Pharmacokinetics (PK): Serum Concentration of Galcanezumab Secondary · Week 2

Pharmacokinetics (PK): Serum Concentration of Galcanezumab

GroupValue95% CI
Galcanezumab 300 mg30,600± 10,700
Pharmacokinetics (PK): Serum Concentration of Galcanezumab Secondary · Week 4

Pharmacokinetics (PK): Serum Concentration of Galcanezumab

GroupValue95% CI
Galcanezumab 300 mg20,200± 6780

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 1 Year 7 Months. Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo (Double-Blind Treatment Phase)
Serious: 3/120 (3%)
Deaths: 0/120
Galcanezumab 300 mg (Double-Blind Treatment Phase)
Serious: 2/117 (2%)
Deaths: 0/117
Placebo/GMB 300 mg (Open-Label Treatment Phase)
Serious: 11/116 (9%)
Deaths: 0/116
GMB 300 mg/GMB 300 mg (Open-Label Treatment Phase)
Serious: 10/113 (9%)
Deaths: 0/113
Placebo (Post-Treatment Phase)
Serious: 0/2 (0%)
Deaths: 0/2
Galcanezumab 300 mg (Post-Treatment Phase)
Serious: 0/4 (0%)
Deaths: 0/4
Placebo/GMB 300 mg (Post-Treatment Phase)
Serious: 0/93 (0%)
Deaths: 0/93
GMB 300 mg/GMB 300 Mg-Post-Treatment Phase
Serious: 5/93 (5%)
Deaths: 0/93

Serious adverse events (31 terms)

ReactionSystemPlacebo (Double-Blind Trea…Galcanezumab 300 mg (Doubl…Placebo/GMB 300 mg (Open-L…GMB 300 mg/GMB 300 mg (Ope…Placebo (Post-Treatment Ph…Galcanezumab 300 mg (Post-…Placebo/GMB 300 mg (Post-T…GMB 300 mg/GMB 300 Mg-Post…
Cluster headacheNervous system disorders
Atrial fibrillationCardiac disorders
PalpitationsCardiac disorders
AmaurosisEye disorders
ConstipationGastrointestinal disorders
MelaenaGastrointestinal disorders
Small intestinal obstructionGastrointestinal disorders
Chest painGeneral disorders
Injection site urticariaGeneral disorders
Non-cardiac chest painGeneral disorders
AppendicitisInfections and infestations
DiverticulitisInfections and infestations
GastroenteritisInfections and infestations
Helicobacter gastritisInfections and infestations
Rectal abscessInfections and infestations
Urinary tract infection bacterialInfections and infestations
Extradural haematomaInjury, poisoning and procedural complications
Kidney ruptureInjury, poisoning and procedural complications
Road traffic accidentInjury, poisoning and procedural complications
RhabdomyolysisMusculoskeletal and connective tissue disorders
Breast cancer stage iiiNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon neoplasmNeoplasms benign, malignant and unspecified (incl cysts and polyps)
MetastasisNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Pituitary tumourNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Cerebral ischaemiaNervous system disorders
Other adverse events (52 terms — click to expand)

ReactionSystemPlacebo (Double-Blind Trea…Galcanezumab 300 mg (Doubl…Placebo/GMB 300 mg (Open-L…GMB 300 mg/GMB 300 mg (Ope…Placebo (Post-Treatment Ph…Galcanezumab 300 mg (Post-…Placebo/GMB 300 mg (Post-T…GMB 300 mg/GMB 300 Mg-Post…
NasopharyngitisInfections and infestations
Injection site painGeneral disorders
Back painMusculoskeletal and connective tissue disorders
Injection site erythemaGeneral disorders
Injection site reactionGeneral disorders
InfluenzaInfections and infestations
FatigueGeneral disorders
Injection site pruritusGeneral disorders
ConstipationGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
SinusitisInfections and infestations
ArthralgiaMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
InsomniaPsychiatric disorders
Influenza like illnessGeneral disorders
Upper respiratory tract infectionInfections and infestations
DepressionPsychiatric disorders
Abdominal painGastrointestinal disorders
BronchitisInfections and infestations
MyalgiaMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
AnxietyPsychiatric disorders
HypertensionVascular disorders
PalpitationsCardiac disorders
TinnitusEar and labyrinth disorders
VertigoEar and labyrinth disorders
Visual impairmentEye disorders
VomitingGastrointestinal disorders
Chest painGeneral disorders
Injection site swellingGeneral disorders
Non-cardiac chest painGeneral disorders
PyrexiaGeneral disorders
Seasonal allergyImmune system disorders
GastroenteritisInfections and infestations
TracheitisInfections and infestations
Urinary tract infectionInfections and infestations
FallInjury, poisoning and procedural complications
Ligament sprainInjury, poisoning and procedural complications

Most-reported serious reactions: Cluster headache, Atrial fibrillation, Palpitations, Amaurosis, Constipation, Melaena, Small intestinal obstruction, Chest pain.

Data from ClinicalTrials.gov NCT02438826 adverse events section.

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. CGRP and the Trigeminal System in Migraine.
    Iyengar S, Johnson KW, Ossipov MH, Aurora SK. · · 2019 · cited 309× · PMID 30982963 · DOI 10.1111/head.13529
  2. Antibodies to watch in 2017.
    Reichert JM. · · 2017 · cited 194× · PMID 27960628 · DOI 10.1080/19420862.2016.1269580
  3. Antibodies to watch in 2018.
    Kaplon H, Reichert JM. · · 2018 · cited 179× · PMID 29300693 · DOI 10.1080/19420862.2018.1415671
  4. Antibodies to watch in 2016.
    Reichert JM. · · 2016 · cited 135× · PMID 26651519 · DOI 10.1080/19420862.2015.1125583
  5. Phase 3 randomized, placebo-controlled study of galcanezumab in patients with chronic cluster headache: Results from 3-month double-blind treatment.
    Dodick DW, Goadsby PJ, Lucas C, Jensen R, et al · · 2020 · cited 96× · PMID 32050782 · DOI 10.1177/0333102420905321
  6. New Trends in Migraine Pharmacology: Targeting Calcitonin Gene-Related Peptide (CGRP) With Monoclonal Antibodies.
    Scuteri D, Adornetto A, Rombolà L, Naturale MD, et al · · 2019 · cited 63× · PMID 31024319 · DOI 10.3389/fphar.2019.00363
  7. Spotlight on Anti-CGRP Monoclonal Antibodies in Migraine: The Clinical Evidence to Date.
    Pellesi L, Guerzoni S, Pini LA. · · 2017 · cited 48× · PMID 28409893 · DOI 10.1002/cpdd.345
  8. Migraine and cluster headache - the common link.
    Vollesen AL, Benemei S, Cortese F, Labastida-Ramírez A, et al · · 2018 · cited 45× · PMID 30242519 · DOI 10.1186/s10194-018-0909-4

Verify or expand the search:

Other recruiting trials for Chronic Cluster Headache

Currently open trials in the same condition.

Other Eli Lilly and Company trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02438826.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing