Episodic Cluster Headache
Conditions
Brief summary
The main purpose of this study is to evaluate the efficacy and safety of the study drug known as Galcanezumab in participants with episodic cluster headaches.
Interventions
DRUGGalcanezumab
Administered SC
DRUGPlacebo
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Have a diagnosis of cluster headache as defined by International Headache Society (IHS) International Classification of Headache Disorders (ICHD)-3 beta guidelines with a history of episodic cluster headache with at least two cluster periods lasting from 7 days to 1 year (when untreated) and separated by pain-free remission periods of \>=1 month. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Mean Change From Baseline in Number of Weekly Cluster Headache Attacks | Baseline, Week 1 through Week 3 | Number of cluster headache attacks was recorded daily by study participants in their ePRO Diary. Overall mean change from baseline is derived from the average of weeks 1 to 3 from mixed model repeated measures (MMRM) analysis. Least Square (LS) means were calculated using MMRM model with treatment, sex, pooled investigative site, week, baseline, and treatment by week as fixed effects. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Mean Change From Baseline in Number of Weekly Cluster Headache Attacks | Baseline, Week 1 through Week 8 | Number of cluster headache attacks was recorded daily by study participants in their ePRO Diary. Overall mean change from baseline is derived from the average of weeks 1 to 8 from MMRM analysis. Least Square (LS) means were calculated using MMRM model with treatment, sex, pooled investigative site, week, baseline, and treatment by week as fixed effects. |
| Percentage of Participants Reporting a Score of 1 or 2 on the Patient Global Impression of Improvement (PGI-I) | 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, baseline cluster headache attack category, month, and treatment by month as fixed effects. |
| Percentage of Participants With 50% or Greater Reduction From Baseline in Number of Weekly Cluster Headache Attacks | Baseline, Week 1 through Week 8 | Number of cluster headache attacks was recorded daily by study participants in their ePRO Diary. Mean percentage of participants is derived from the average of weeks 1 to 8 from generalized linear mixed model repeated measures method with treatment, sex, week, treatment by week, and baseline as fixed effects. |
| Percentage of Participants With 30% or Greater Reduction From Baseline in Number of Weekly Cluster Headache Attacks | Baseline, Week 1 through Week 8 | Number of cluster headache attacks was recorded daily by study participants in their ePRO Diary. Mean percentage of participants is derived from the average of weeks 1 to 8 from generalized linear mixed model repeated measures with treatment, sex, week, treatment by week and baseline as fixed effects. |
| Percentage of Participants With 50% or Greater Reduction From Baseline in the Weekly Number of Cluster Headache Attacks | Baseline, Week 3 | Number of cluster headache attacks was recorded daily by study participants in their ePRO Diary. Percentage of participants with 50% or greater reduction from baseline at week 3 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 and baseline value. |
| Percentage of Participants Developing Anti-Drug Antibodies (ADA) to Galcanezumab | Baseline through Week 8 | 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. |
| Percentage of Participants With Suicidal Ideation Assessed by Columbia - Suicide Severity Rating Scale (C-SSRS) | Month 1 through Month 6 | 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. |
| Percentage of Participants With Suicidal Behaviors Assessed by Columbia - Suicide Severity Rating Scale (C-SSRS) | Month 1 through Month 6 | 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. |
| Pharmacokinetics (PK): Serum Concentration of Galcanezumab | Week 4 | — |
Countries
Belgium, Canada, Denmark, Finland, France, Germany, Greece, Italy, Netherlands, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo once a month for 2 months by SC injection.
Participants did not receive any intervention during post treatment follow-up phase. | 57 |
| Galcanezumab 300mg Participants received Galcanezumab 300mg once a month for two months by SC injection.
Participants did not receive any intervention during post treatment follow-up phase. | 49 |
| Total | 106 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Post Treatment Follow-up Phase | Lack of Efficacy | 1 | 1 |
| Post Treatment Follow-up Phase | Lost to Follow-up | 1 | 0 |
| Post Treatment Follow-up Phase | Protocol Violation | 1 | 0 |
| Post Treatment Follow-up Phase | Withdrawal by Subject | 0 | 1 |
| Treatment Phase | Adverse Event | 1 | 2 |
| Treatment Phase | Lack of Efficacy | 8 | 1 |
| Treatment Phase | Lost to Follow-up | 1 | 0 |
| Treatment Phase | Protocol Violation(did not receive drug) | 0 | 3 |
| Treatment Phase | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Placebo | Galcanezumab 300mg | Total |
|---|---|---|---|
| Age, Continuous | 45.40 years STANDARD_DEVIATION 11.32 | 47.49 years STANDARD_DEVIATION 10.74 | 46.37 years STANDARD_DEVIATION 11.05 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 3 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 45 Participants | 41 Participants | 86 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 8 Participants | 5 Participants | 13 Participants |
| Lifetime suicidal behavior prior to screening | 0 Participants | 1 Participants | 1 Participants |
| Lifetime suicidal ideation prior to screening | 5 Participants | 9 Participants | 14 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 3 Participants | 8 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 47 Participants | 43 Participants | 90 Participants |
| Region of Enrollment Belgium | 4 Participants | 4 Participants | 8 Participants |
| Region of Enrollment Canada | 1 Participants | 1 Participants | 2 Participants |
| Region of Enrollment Denmark | 2 Participants | 1 Participants | 3 Participants |
| Region of Enrollment Finland | 2 Participants | 1 Participants | 3 Participants |
| Region of Enrollment France | 5 Participants | 4 Participants | 9 Participants |
| Region of Enrollment Germany | 4 Participants | 2 Participants | 6 Participants |
| Region of Enrollment Greece | 1 Participants | 2 Participants | 3 Participants |
| Region of Enrollment Italy | 11 Participants | 9 Participants | 20 Participants |
| Region of Enrollment Netherlands | 1 Participants | 2 Participants | 3 Participants |
| Region of Enrollment Spain | 7 Participants | 6 Participants | 13 Participants |
| Region of Enrollment United Kingdom | 1 Participants | 1 Participants | 2 Participants |
| Region of Enrollment United States | 18 Participants | 16 Participants | 34 Participants |
| Sex: Female, Male Female | 10 Participants | 8 Participants | 18 Participants |
| Sex: Female, Male Male | 47 Participants | 41 Participants | 88 Participants |
| Weekly Cluster Headache Attacks | 17.30 Cluster Headache Attacks per week STANDARD_DEVIATION 10.05 | 17.82 Cluster Headache Attacks per week STANDARD_DEVIATION 10.12 | 17.54 Cluster Headache Attacks per week STANDARD_DEVIATION 10.04 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 57 | 0 / 49 | 0 / 50 | 0 / 47 |
| other Total, other adverse events | 4 / 57 | 7 / 49 | 3 / 50 | 1 / 47 |
| serious Total, serious adverse events | 0 / 57 | 0 / 49 | 2 / 50 | 0 / 47 |
Outcome results
Primary
Overall Mean Change From Baseline in Number of Weekly Cluster Headache Attacks
Number of cluster headache attacks was recorded daily by study participants in their ePRO Diary. Overall mean change from baseline is derived from the average of weeks 1 to 3 from mixed model repeated measures (MMRM) analysis. Least Square (LS) means were calculated using MMRM model with treatment, sex, pooled investigative site, week, baseline, and treatment by week as fixed effects.
Time frame: Baseline, Week 1 through Week 3
Population: All randomized participants who received at least one dose of study drug and had baseline and at least one post baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Overall Mean Change From Baseline in Number of Weekly Cluster Headache Attacks | -5.22 Cluster Headache Attacks per Week | Standard Error 1.33 |
| Galcanezumab 300mg | Overall Mean Change From Baseline in Number of Weekly Cluster Headache Attacks | -8.69 Cluster Headache Attacks per Week | Standard Error 1.42 |
p-value: 0.03695% CI: [-6.72, -0.23]Mixed Models Analysis
Secondary
Overall Mean Change From Baseline in Number of Weekly Cluster Headache Attacks
Number of cluster headache attacks was recorded daily by study participants in their ePRO Diary. Overall mean change from baseline is derived from the average of weeks 1 to 8 from MMRM analysis. Least Square (LS) means were calculated using MMRM model with treatment, sex, pooled investigative site, week, baseline, and treatment by week as fixed effects.
Time frame: Baseline, Week 1 through Week 8
Population: All randomized participants who received at least one dose of study drug and had baseline and at least one post baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Overall Mean Change From Baseline in Number of Weekly Cluster Headache Attacks | -9.97 Cluster Headache Attacks per Week | Standard Error 0.95 |
| Galcanezumab 300mg | Overall Mean Change From Baseline in Number of Weekly Cluster Headache Attacks | -10.80 Cluster Headache Attacks per Week | Standard Error 1 |
p-value: 0.49395% CI: [-3.23, 1.57]Mixed Models Analysis
Secondary
Percentage of Participants Developing Anti-Drug Antibodies (ADA) to Galcanezumab
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.
Time frame: Baseline through Week 8
Population: All randomized participants who received at least one dose of study drug and had non-missing baseline ADA result, and at least one non-missing post baseline ADA result.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Developing Anti-Drug Antibodies (ADA) to Galcanezumab | 0 percentage of participants |
| Galcanezumab 300mg | Percentage of Participants Developing Anti-Drug Antibodies (ADA) to Galcanezumab | 0 percentage of participants |
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, baseline cluster headache attack category, month, and treatment by month as fixed effects.
Time frame: Week 8
Population: All randomized participants who received at least one dose of study drug and had PGI-I measurement at week 8.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Reporting a Score of 1 or 2 on the Patient Global Impression of Improvement (PGI-I) | 66.1 percentage of participants |
| Galcanezumab 300mg | Percentage of Participants Reporting a Score of 1 or 2 on the Patient Global Impression of Improvement (PGI-I) | 71.9 percentage of participants |
p-value: 0.57595% CI: [0.502, 3.426]Mixed Models Analysis
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, baseline cluster headache attack category, month, and treatment by month as fixed effects.
Time frame: Week 4
Population: All randomized participants who received at least one dose of study drug and had PGI-I measurement at week4.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Reporting a Score of 1 or 2 on the Patient Global Impression of Improvement (PGI-I) | 46.4 percentage of participants |
| Galcanezumab 300mg | Percentage of Participants Reporting a Score of 1 or 2 on the Patient Global Impression of Improvement (PGI-I) | 72.5 percentage of participants |
p-value: 0.01695% CI: [1.242, 7.469]Mixed Models Analysis
Secondary
Percentage of Participants With 30% or Greater Reduction From Baseline in Number of Weekly Cluster Headache Attacks
Number of cluster headache attacks was recorded daily by study participants in their ePRO Diary. Mean percentage of participants is derived from the average of weeks 1 to 8 from generalized linear mixed model repeated measures with treatment, sex, week, treatment by week and baseline as fixed effects.
Time frame: Baseline, Week 1 through Week 8
Population: All randomized participants who received at least one dose of study drug and had baseline and at least one post baseline measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With 30% or Greater Reduction From Baseline in Number of Weekly Cluster Headache Attacks | 78.9 percentage of participants |
| Galcanezumab 300mg | Percentage of Participants With 30% or Greater Reduction From Baseline in Number of Weekly Cluster Headache Attacks | 77.7 percentage of participants |
p-value: 0.84195% CI: [0.449, 1.923]Mixed Models Analysis
Secondary
Percentage of Participants With 50% or Greater Reduction From Baseline in Number of Weekly Cluster Headache Attacks
Number of cluster headache attacks was recorded daily by study participants in their ePRO Diary. Mean percentage of participants is derived from the average of weeks 1 to 8 from generalized linear mixed model repeated measures method with treatment, sex, week, treatment by week, and baseline as fixed effects.
Time frame: Baseline, Week 1 through Week 8
Population: All randomized participants who received at least one dose of study drug and had baseline and at least one post baseline measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With 50% or Greater Reduction From Baseline in Number of Weekly Cluster Headache Attacks | 70.4 percentage of participants |
| Galcanezumab 300mg | Percentage of Participants With 50% or Greater Reduction From Baseline in Number of Weekly Cluster Headache Attacks | 69.6 percentage of participants |
p-value: 0.9195% CI: [0.512, 1.819]Mixed Models Analysis
Secondary
Percentage of Participants With 50% or Greater Reduction From Baseline in the Weekly Number of Cluster Headache Attacks
Number of cluster headache attacks was recorded daily by study participants in their ePRO Diary. Percentage of participants with 50% or greater reduction from baseline at week 3 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 and baseline value.
Time frame: Baseline, Week 3
Population: All randomized participants who received at least one dose of study drug and had baseline and at least one post baseline measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With 50% or Greater Reduction From Baseline in the Weekly Number of Cluster Headache Attacks | 52.63 percentage of participants |
| Galcanezumab 300mg | Percentage of Participants With 50% or Greater Reduction From Baseline in the Weekly Number of Cluster Headache Attacks | 71.43 percentage of participants |
p-value: 0.046ANCOVA
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.
Time frame: Month 1 through Month 6
Population: All randomized participants who received at least one dose of study drug and had at least one post baseline C-SSRS assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Suicidal Behaviors Assessed by Columbia - Suicide Severity Rating Scale (C-SSRS) | 0 percentage of participants |
| Galcanezumab 300mg | Percentage of Participants With Suicidal Behaviors Assessed by Columbia - Suicide Severity Rating Scale (C-SSRS) | 0 percentage of participants |
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.
Time frame: Month 1 through Month 6
Population: All randomized participants who received at least one dose of study drug and had at least one post baseline C-SSRS assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Suicidal Ideation Assessed by Columbia - Suicide Severity Rating Scale (C-SSRS) | 0 percentage of participants |
| Galcanezumab 300mg | Percentage of Participants With Suicidal Ideation Assessed by Columbia - Suicide Severity Rating Scale (C-SSRS) | 0 percentage of participants |
Secondary
Pharmacokinetics (PK): Serum Concentration of Galcanezumab
Time frame: Week 4
Population: All randomized participants who received at least one dose of study drug and had measurable PK samples.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacokinetics (PK): Serum Concentration of Galcanezumab | 20200 Nanogram per Milliliter (ng/mL) | Standard Deviation 6880 |
Secondary
Pharmacokinetics (PK): Serum Concentration of Galcanezumab
Time frame: Week 8
Population: All randomized participants who received at least one dose of study drug and had measurable PK samples.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacokinetics (PK): Serum Concentration of Galcanezumab | 26400 Nanogram per Milliliter (ng/mL) | Standard Deviation 11200 |