Trial Outcomes & Findings for A Study Of Galcanezumab In Participants With Episodic Cluster Headache (NCT NCT02397473)

NCT ID: NCT02397473

Last Updated: 2019-09-09

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

109 participants

Primary outcome timeframe

Baseline, Week 1 through Week 3

Results posted on

2019-09-09

Participant Flow

Participant milestones

Participant milestones
Measure
Placebo
Participants received placebo once a month for 2 months by subcutaneous (SC) injection. Participants did not receive any intervention during post treatment follow-up phase.
Galcanezumab 300mg
Participants received Galcanezumab 300mg once a month for two months by subcutaneous (SC) injection. Participants did not receive any intervention during post treatment follow-up phase.
Treatment Phase
STARTED
57
52
Treatment Phase
Received at Least One Dose of Study Drug
57
49
Treatment Phase
COMPLETED
45
45
Treatment Phase
NOT COMPLETED
12
7
Post Treatment Follow-up Phase
STARTED
50
47
Post Treatment Follow-up Phase
COMPLETED
47
45
Post Treatment Follow-up Phase
NOT COMPLETED
3
2

Reasons for withdrawal

Reasons for withdrawal
Measure
Placebo
Participants received placebo once a month for 2 months by subcutaneous (SC) injection. Participants did not receive any intervention during post treatment follow-up phase.
Galcanezumab 300mg
Participants received Galcanezumab 300mg once a month for two months by subcutaneous (SC) injection. Participants did not receive any intervention during post treatment follow-up phase.
Treatment Phase
Adverse Event
1
2
Treatment Phase
Lack of Efficacy
8
1
Treatment Phase
Lost to Follow-up
1
0
Treatment Phase
Withdrawal by Subject
2
1
Treatment Phase
Protocol Violation(did not receive drug)
0
3
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

Baseline Characteristics

A Study Of Galcanezumab In Participants With Episodic Cluster Headache

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Placebo
n=57 Participants
Participants received placebo once a month for 2 months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.
Galcanezumab 300mg
n=49 Participants
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.
Total
n=106 Participants
Total of all reporting groups
Age, Continuous
45.40 years
STANDARD_DEVIATION 11.32 • n=93 Participants
47.49 years
STANDARD_DEVIATION 10.74 • n=4 Participants
46.37 years
STANDARD_DEVIATION 11.05 • n=27 Participants
Sex: Female, Male
Female
10 Participants
n=93 Participants
8 Participants
n=4 Participants
18 Participants
n=27 Participants
Sex: Female, Male
Male
47 Participants
n=93 Participants
41 Participants
n=4 Participants
88 Participants
n=27 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
4 Participants
n=93 Participants
3 Participants
n=4 Participants
7 Participants
n=27 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
45 Participants
n=93 Participants
41 Participants
n=4 Participants
86 Participants
n=27 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
8 Participants
n=93 Participants
5 Participants
n=4 Participants
13 Participants
n=27 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=93 Participants
0 Participants
n=4 Participants
0 Participants
n=27 Participants
Race (NIH/OMB)
Asian
1 Participants
n=93 Participants
1 Participants
n=4 Participants
2 Participants
n=27 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=93 Participants
0 Participants
n=4 Participants
0 Participants
n=27 Participants
Race (NIH/OMB)
Black or African American
4 Participants
n=93 Participants
2 Participants
n=4 Participants
6 Participants
n=27 Participants
Race (NIH/OMB)
White
47 Participants
n=93 Participants
43 Participants
n=4 Participants
90 Participants
n=27 Participants
Race (NIH/OMB)
More than one race
5 Participants
n=93 Participants
3 Participants
n=4 Participants
8 Participants
n=27 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=93 Participants
0 Participants
n=4 Participants
0 Participants
n=27 Participants
Region of Enrollment
Greece
1 Participants
n=93 Participants
2 Participants
n=4 Participants
3 Participants
n=27 Participants
Region of Enrollment
Canada
1 Participants
n=93 Participants
1 Participants
n=4 Participants
2 Participants
n=27 Participants
Region of Enrollment
Netherlands
1 Participants
n=93 Participants
2 Participants
n=4 Participants
3 Participants
n=27 Participants
Region of Enrollment
Belgium
4 Participants
n=93 Participants
4 Participants
n=4 Participants
8 Participants
n=27 Participants
Region of Enrollment
United States
18 Participants
n=93 Participants
16 Participants
n=4 Participants
34 Participants
n=27 Participants
Region of Enrollment
Finland
2 Participants
n=93 Participants
1 Participants
n=4 Participants
3 Participants
n=27 Participants
Region of Enrollment
Denmark
2 Participants
n=93 Participants
1 Participants
n=4 Participants
3 Participants
n=27 Participants
Region of Enrollment
Italy
11 Participants
n=93 Participants
9 Participants
n=4 Participants
20 Participants
n=27 Participants
Region of Enrollment
United Kingdom
1 Participants
n=93 Participants
1 Participants
n=4 Participants
2 Participants
n=27 Participants
Region of Enrollment
France
5 Participants
n=93 Participants
4 Participants
n=4 Participants
9 Participants
n=27 Participants
Region of Enrollment
Germany
4 Participants
n=93 Participants
2 Participants
n=4 Participants
6 Participants
n=27 Participants
Region of Enrollment
Spain
7 Participants
n=93 Participants
6 Participants
n=4 Participants
13 Participants
n=27 Participants
Weekly Cluster Headache Attacks
17.30 Cluster Headache Attacks per week
STANDARD_DEVIATION 10.05 • n=93 Participants
17.82 Cluster Headache Attacks per week
STANDARD_DEVIATION 10.12 • n=4 Participants
17.54 Cluster Headache Attacks per week
STANDARD_DEVIATION 10.04 • n=27 Participants
Lifetime suicidal ideation prior to screening
5 Participants
n=93 Participants
9 Participants
n=4 Participants
14 Participants
n=27 Participants
Lifetime suicidal behavior prior to screening
0 Participants
n=93 Participants
1 Participants
n=4 Participants
1 Participants
n=27 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Placebo
n=57 Participants
Participants received placebo once a month for two months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.
Galcanezumab 300mg
n=49 Participants
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.
Overall Mean Change From Baseline in Number of Weekly Cluster Headache Attacks
-5.22 Cluster Headache Attacks per Week
Standard Error 1.33
-8.69 Cluster Headache Attacks per Week
Standard Error 1.42

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Placebo
n=57 Participants
Participants received placebo once a month for two months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.
Galcanezumab 300mg
n=49 Participants
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.
Percentage of Participants With 50% or Greater Reduction From Baseline in the Weekly Number of Cluster Headache Attacks
52.63 percentage of participants
71.43 percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Placebo
n=57 Participants
Participants received placebo once a month for two months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.
Galcanezumab 300mg
n=49 Participants
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.
Overall Mean Change From Baseline in Number of Weekly Cluster Headache Attacks
-9.97 Cluster Headache Attacks per Week
Standard Error 0.95
-10.80 Cluster Headache Attacks per Week
Standard Error 1.00

SECONDARY outcome

Timeframe: Week 4

Population: All randomized participants who received at least one dose of study drug and had PGI-I measurement at week4.

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.

Outcome measures

Outcome measures
Measure
Placebo
n=49 Participants
Participants received placebo once a month for two months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.
Galcanezumab 300mg
n=44 Participants
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.
Percentage of Participants Reporting a Score of 1 or 2 on the Patient Global Impression of Improvement (PGI-I)
46.4 percentage of participants
72.5 percentage of participants

SECONDARY outcome

Timeframe: Week 8

Population: All randomized participants who received at least one dose of study drug and had PGI-I measurement at 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, baseline cluster headache attack category, month, and treatment by month as fixed effects.

Outcome measures

Outcome measures
Measure
Placebo
n=40 Participants
Participants received placebo once a month for two months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.
Galcanezumab 300mg
n=38 Participants
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.
Percentage of Participants Reporting a Score of 1 or 2 on the Patient Global Impression of Improvement (PGI-I)
66.1 percentage of participants
71.9 percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Placebo
n=57 Participants
Participants received placebo once a month for two months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.
Galcanezumab 300mg
n=49 Participants
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.
Percentage of Participants With 50% or Greater Reduction From Baseline in Number of Weekly Cluster Headache Attacks
70.4 percentage of participants
69.6 percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Placebo
n=57 Participants
Participants received placebo once a month for two months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.
Galcanezumab 300mg
n=49 Participants
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.
Percentage of Participants With 30% or Greater Reduction From Baseline in Number of Weekly Cluster Headache Attacks
78.9 percentage of participants
77.7 percentage of participants

SECONDARY outcome

Timeframe: Week 4

Population: All randomized participants who received at least one dose of study drug and had measurable PK samples.

Outcome measures

Outcome measures
Measure
Placebo
n=45 Participants
Participants received placebo once a month for two months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.
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.
Pharmacokinetics (PK): Serum Concentration of Galcanezumab
20200 Nanogram per Milliliter (ng/mL)
Standard Deviation 6880

SECONDARY outcome

Timeframe: Week 8

Population: All randomized participants who received at least one dose of study drug and had measurable PK samples.

Outcome measures

Outcome measures
Measure
Placebo
n=45 Participants
Participants received placebo once a month for two months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.
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.
Pharmacokinetics (PK): Serum Concentration of Galcanezumab
26400 Nanogram per Milliliter (ng/mL)
Standard Deviation 11200

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Placebo
n=53 Participants
Participants received placebo once a month for two months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.
Galcanezumab 300mg
n=48 Participants
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.
Percentage of Participants Developing Anti-Drug Antibodies (ADA) to Galcanezumab
0 percentage of participants
0 percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Placebo
n=54 Participants
Participants received placebo once a month for two months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.
Galcanezumab 300mg
n=49 Participants
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.
Percentage of Participants With Suicidal Ideation Assessed by Columbia - Suicide Severity Rating Scale (C-SSRS)
0 percentage of participants
0 percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Placebo
n=54 Participants
Participants received placebo once a month for two months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.
Galcanezumab 300mg
n=49 Participants
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.
Percentage of Participants With Suicidal Behaviors Assessed by Columbia - Suicide Severity Rating Scale (C-SSRS)
0 percentage of participants
0 percentage of participants

Adverse Events

Placebo - Treatment Phase

Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths

Galcanezumab 300mg - Treatment Phase

Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths

Placebo - Post Treatment Phase

Serious events: 2 serious events
Other events: 3 other events
Deaths: 0 deaths

Galcanezumab 300mg - Post Treatment Phase

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Placebo - Treatment Phase
n=57 participants at risk
Participants received placebo once a month for two months by SC injection.
Galcanezumab 300mg - Treatment Phase
n=49 participants at risk
Participants received Galcanezumab 300mg once a month for two months by SC injection.
Placebo - Post Treatment Phase
n=50 participants at risk
Participants didn't receive any intervention.
Galcanezumab 300mg - Post Treatment Phase
n=47 participants at risk
Participants didn't receive any intervention.
Nervous system disorders
Cluster headache
0.00%
0/57 • 6 Months
0.00%
0/49 • 6 Months
2.0%
1/50 • Number of events 1 • 6 Months
0.00%
0/47 • 6 Months
Renal and urinary disorders
Nephrolithiasis
0.00%
0/57 • 6 Months
0.00%
0/49 • 6 Months
2.0%
1/50 • Number of events 1 • 6 Months
0.00%
0/47 • 6 Months

Other adverse events

Other adverse events
Measure
Placebo - Treatment Phase
n=57 participants at risk
Participants received placebo once a month for two months by SC injection.
Galcanezumab 300mg - Treatment Phase
n=49 participants at risk
Participants received Galcanezumab 300mg once a month for two months by SC injection.
Placebo - Post Treatment Phase
n=50 participants at risk
Participants didn't receive any intervention.
Galcanezumab 300mg - Post Treatment Phase
n=47 participants at risk
Participants didn't receive any intervention.
General disorders
Injection site pain
0.00%
0/57 • 6 Months
8.2%
4/49 • Number of events 4 • 6 Months
0.00%
0/50 • 6 Months
0.00%
0/47 • 6 Months
Infections and infestations
Nasopharyngitis
1.8%
1/57 • Number of events 1 • 6 Months
6.1%
3/49 • Number of events 3 • 6 Months
6.0%
3/50 • Number of events 3 • 6 Months
2.1%
1/47 • Number of events 1 • 6 Months
Musculoskeletal and connective tissue disorders
Back pain
5.3%
3/57 • Number of events 3 • 6 Months
0.00%
0/49 • 6 Months
0.00%
0/50 • 6 Months
0.00%
0/47 • 6 Months

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

  • Principal investigator is a sponsor employee All information provided to Investigator \&/or Institution by Lilly or Lilly-designated representatives, or generated by Investigator \&/or institution in connection with Study, will be kept in confidence and not used for any purpose not expressly provided in the Agreement for at least 5 years after termination or conclusion of Study, except to the extent that Lilly gives Investigator \&/or Institution written permission or particular information is required by laws or regulations to be disclosed.
  • Publication restrictions are in place

Restriction type: OTHER