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NCT02163993

A Study of Galcanezumab (LY2951742) in Participants With Migraine Headache

Completed Phase 2 Results posted Last updated 23 November 2018
What this trial tests

Phase 2 trial testing Galcanezumab in Migraine Headache in 414 participants. Completed in 12 February 2018.

Timeline
7 July 2014
Primary endpoint
19 August 2015
12 February 2018

Quick facts

Lead sponsorEli Lilly and Company
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment414
Start date7 July 2014
Primary completion19 August 2015
Estimated completion12 February 2018
Sites40 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Eli Lilly and Company — full company profile →

Who can join

Adults 18 to 65, any sex, with Migraine 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.

Mean Change From Baseline in the Number of Migraine Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase Primary · Baseline, 12 Weeks

The criteria for a migraine headache was adapted from the standard International Headache Society (IHS) International Classification of Headache Disorders (ICHD)-3 beta. The definition of a migraine headache was a headache with or without aura, of ≥30 minutes (min) duration, and with both ("A" and "B") required features from the IHS ICHD-3 beta definition. Required feature "A" includes at least 2 of the following headache characteristics: unilateral location, pulsatile quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity. Required feat

GroupValue95% CI
Placebo-3.66± 0.28
5mg Galcanezumab-4.23± 0.37
50mg Galcanezumab-3.92± 0.36
120mg Galcanezumab-4.80± 0.37
300mg Galcanezumab-4.28± 0.39
Mean Change From Baseline in Number of Migraine Attacks in the Last 28-Day Period of the 12-Week Treatment Phase Secondary · Baseline, 12 Weeks

A migraine attack was defined as beginning on any day a migraine headache day was recorded and ending when a migraine headache-free day occurred. The criteria was adapted from the standard IHS ICHD-3 beta definition. The definition of a migraine headache was a headache with or without aura, of ≥30 minutes (min) duration, and with both ("A" and "B") required features from the IHS ICHD-3 beta definition. Required feature "A" includes at least 2 of the following headache characteristics: unilateral location, pulsatile quality, moderate or severe pain intensity, or aggravation by or causing avoida

GroupValue95% CI
Placebo-2.65± 0.17
5mg Galcanezumab-2.98± 0.23
50mg Galcanezumab-2.87± 0.22
120mg Galcanezumab-3.46± 0.23
300mg Galcanezumab-3.01± 0.23
Percentage of Participants With ≥50% Reduction in Number of Migraine Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase Secondary · Week 12

The criteria for a migraine headache was adapted from the standard International Headache Society (IHS) International Classification of Headache Disorders (ICHD)-3 beta definition. The definition of a migraine headache was a headache with or without aura, of ≥30 minutes (min) duration, and with both ("A" and "B") required features from the IHS ICHD-3 beta definition. Required feature "A" includes at least 2 of the following headache characteristics: unilateral location, pulsatile quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity. Re

GroupValue95% CI
Placebo60.9
5mg Galcanezumab75.4
50mg Galcanezumab65.5
120mg Galcanezumab76.5
300mg Galcanezumab70.1
Mean Change From Baseline in the Number of Days of Medication Use for the Treatment of Migraine Headache in the Last 28-Day Period of the 12-Week Treatment Phase Secondary · Baseline, 12 Weeks

A migraine attack was defined as beginning on any day a migraine headache day was recorded and ending when a migraine headache-free day occurred. The criteria was adapted from the standard IHS ICHD-3 beta definition. The definition of a migraine headache was a headache with or without aura, of ≥30 minutes (min) duration, and with both ("A" and "B") required features from the IHS ICHD-3 beta definition. Required feature "A" includes at least 2 of the following headache characteristics: unilateral location, pulsatile quality, moderate or severe pain intensity, or aggravation by or causing avoida

GroupValue95% CI
Placebo-2.51± 0.23
5mg Galcanezumab-3.27± 0.32
50mg Galcanezumab-2.58± 0.31
120mg Galcanezumab-3.59± 0.31
300mg Galcanezumab-3.15± 0.32
Mean Change From Baseline in Number of Headache Hours in the Last 28-Day Period of the 12-Week Treatment Phase Secondary · Baseline, 12 Weeks

Number of headache hours calculated as the total number of headache hours in a 28-day period on which a headache occurred. Least Squares (LS) means was determined by mixed model repeated measures (MMRM) methodology with treatment, pooled investigative site, period, and treatment-by-period interaction, baseline and baseline-by-period interaction.

GroupValue95% CI
Placebo-16.56± 1.73
5mg Galcanezumab-20.15± 2.45
50mg Galcanezumab-19.38± 2.35
120mg Galcanezumab-22.29± 2.39
300mg Galcanezumab-24.45± 2.42
Change From Baseline to 12 Week Endpoint in Migraine Specific Quality of Life (MSQL) Questionnaire Total Scores Secondary · Baseline, 12 Weeks

MSQL consists of 14 questions across 3 dimensions (role function-restrictive, role function-preventive, and emotional function). All question values range from 1 to 6. Participants rated each item from 1 (none of the time) to 6 (all of the time). Since each item was presented as a negative statement, participant responses were recorded before item scores were calculated. Then, dimension scores were calculated as the sum of the recorded items for that specific dimension. Each dimension score was transformed into a score that ranged from 0 to 100. The transformation formula for the restrictive f

GroupValue95% CI
Placebo21.08± 1.82
5mg Galcanezumab27.53± 2.53
50mg Galcanezumab25.35± 2.46
120mg Galcanezumab30.23± 2.58
300mg Galcanezumab27.49± 2.51
Change From Baseline to 12 Week Endpoint in the Headache Impact Test-6™ (HIT-6™) Scores Secondary · Baseline, 12 Weeks

The HIT-6 consists of 6 questions to measure the impact of headaches on the participants ability to function on the job, at school, at home and in social situations. A score to each question will be assigned as follows: never - 6, rarely - 8, sometimes - 10, very often - 11, and always - 13. The composite score is calculated as the sum of the scores for all 6 questions, the total score ranges between 36 and 78 with higher total scores reflecting more severe impact of headaches. LS means was determined by ANCOVA with treatment, pooled investigative site and baseline.

GroupValue95% CI
Placebo-7.26± 0.79
5mg Galcanezumab-9.26± 1.09
50mg Galcanezumab-8.46± 1.06
120mg Galcanezumab-9.95± 1.12
300mg Galcanezumab-8.27± 1.09
Serum Concentration of Galcanezumab Secondary · 12 Weeks

Blood serum concentrations of galcanezumab.

GroupValue95% CI
5mg Galcanezumab840± 602
50mg Galcanezumab4650± 2430
120mg Galcanezumab13200± 7060
300mg Galcanezumab32100± 19100
Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP) Secondary · 12 Weeks

CGRP has been shown to be involved in the pathophysiology of migraine through dilation of cerebral and dural blood vessels, release of inflammatory mediators, and transmission of nociceptive (pain) information from intracranial blood vessels to the nervous system (Villalón and Olesen 2009). In migraineurs, serum concentrations of CGRP are significantly elevated during migraine attacks (Goadsby et al. 1990; Goadsby and Edvinsson 1993).

GroupValue95% CI
Placebo0.1810± 0.1030
5mg Galcanezumab0.4750± 0.3940
50mg Galcanezumab1.5700± 0.7010
120mg Galcanezumab2.8000± 1.2200
300mg Galcanezumab3.8300± 1.3100
Percentage of Participants Developing Anti-drug Antibodies to Galcanezumab Secondary · Baseline through 12 Weeks

The percent of participants with treatment emergent Anti-drug Antibodies (ADA) were assessed at week 1 to 12. A participant was considered to have treatment-emergent Galcanezumab ADA if the participant had at least 1 titer that was treatment-emergent relative to baseline, defined as any of the following: A negative baseline ADA result and a subsequent positive post-baseline ADA result with a titer \>=20; or a positive ADA results and a subsequent positive post-baseline ADA results with a 4-fold or greater increase in titer from the baseline measurement.

GroupValue95% CI
Placebo2.2
5mg Galcanezumab7.7
50mg Galcanezumab4.6
120mg Galcanezumab2.9
300mg Galcanezumab3.1
Percentage of Participants With Suicidal Ideation and Behaviors Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) Scores Secondary · Baseline through Week 12

The 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.

Suicidal Ideation
GroupValue95% CI
Placebo0
5mg Galcanezumab0
50mg Galcanezumab0
120mg Galcanezumab0
300mg Galcanezumab1.52
Suicidal Behavior
GroupValue95% CI
Placebo0
5mg Galcanezumab0
50mg Galcanezumab0
120mg Galcanezumab0
300mg Galcanezumab0
Mean Change From Baseline in the Number of Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase Secondary · Baseline, 12 Weeks

Number of calendar days on which a headache lasts ≥4 hours which includes migraines, probable migraines (PM) and nonmigraines. Criteria for migraine headache (MH) was adapted from standard IHS ICHD-3 beta definition. It is defined as headache with or without aura, of ≥30 min duration, and with both ("A" and "B") required features from IHS ICHD-3 beta definition. Required feature "A" includes ≥2 of following headache characteristics: unilateral location, pulsatile quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity. Required feature "B

GroupValue95% CI
Placebo-2.47± 0.22
5mg Galcanezumab-2.81± 0.32
50mg Galcanezumab-2.57± 0.30
120mg Galcanezumab-3.11± 0.31
300mg Galcanezumab-3.37± 0.31

Adverse events — posted to ClinicalTrials.gov

Time frame: Up To 24 Weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo - Treatment Phase
Serious: 0/137 (0%)
Deaths:
5mg Galcanezumab-Treatment Phase
Serious: 0/68 (0%)
Deaths:
50mg Galcanezumab-Treatment Phase
Serious: 0/68 (0%)
Deaths:
120mg Galcanezumab-Treatment Phase
Serious: 1/70 (1%)
Deaths:
300mg Galcanezumab-Treatment Phase
Serious: 1/67 (1%)
Deaths:
Placebo - Post-Treatment Phase
Serious: 0/125 (0%)
Deaths:
5mg Galcanezumab-Post-Treatment Phase
Serious: 1/61 (2%)
Deaths:
50mg Galcanezumab-Post-Treatment Phase
Serious: 0/66 (0%)
Deaths:
120mg Galcanezumab-Post-Treatment Phase
Serious: 0/63 (0%)
Deaths:
300mg Galcanezumab-Post-Treatment Phase
Serious: 1/65 (2%)
Deaths:

Serious adverse events (4 terms)

ReactionSystemPlacebo - Treatment Phase5mg Galcanezumab-Treatment…50mg Galcanezumab-Treatmen…120mg Galcanezumab-Treatme…300mg Galcanezumab-Treatme…Placebo - Post-Treatment P…5mg Galcanezumab-Post-Trea…50mg Galcanezumab-Post-Tre…120mg Galcanezumab-Post-Tr…300mg Galcanezumab-Post-Tr…
Crohn's diseaseGastrointestinal disorders
AppendicitisInfections and infestations
Suicidal IdeationPsychiatric disorders
Ankyloglossia CongenitalCongenital, familial and genetic disorders
Other adverse events (5 terms — click to expand)

ReactionSystemPlacebo - Treatment Phase5mg Galcanezumab-Treatment…50mg Galcanezumab-Treatmen…120mg Galcanezumab-Treatme…300mg Galcanezumab-Treatme…Placebo - Post-Treatment P…5mg Galcanezumab-Post-Trea…50mg Galcanezumab-Post-Tre…120mg Galcanezumab-Post-Tr…300mg Galcanezumab-Post-Tr…
Upper respiratory tract infectionInfections and infestations
Injection site painGeneral disorders
NasopharyngitisInfections and infestations
NauseaGastrointestinal disorders
DysmenorrhoeaReproductive system and breast disorders

Most-reported serious reactions: Crohn's disease, Appendicitis, Suicidal Ideation, Ankyloglossia Congenital.

Data from ClinicalTrials.gov NCT02163993 adverse events section.

Sponsor's own description

The main purpose of this study is to evaluate whether the study drug known as galcanezumab is safe and effective in the prevention of migraine headaches.

Publications & conference data

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

  1. European Headache Federation guideline on the use of monoclonal antibodies targeting the calcitonin gene related peptide pathway for migraine prevention - 2022 update.
    Sacco S, Amin FM, Ashina M, Bendtsen L, et al · · 2022 · cited 250× · PMID 35690723 · DOI 10.1186/s10194-022-01431-x
  2. Effect of Different Doses of Galcanezumab vs Placebo for Episodic Migraine Prevention: A Randomized Clinical Trial.
    Skljarevski V, Oakes TM, Zhang Q, Ferguson MB, et al · · 2018 · cited 116× · PMID 29255900 · DOI 10.1001/jamaneurol.2017.3859
  3. CGRP monoclonal antibodies in migraine: an efficacy and tolerability comparison with standard prophylactic drugs.
    Vandervorst F, Van Deun L, Van Dycke A, Paemeleire K, et al · · 2021 · cited 87× · PMID 34696711 · DOI 10.1186/s10194-021-01335-2
  4. Efficacy and safety of calcitonin-gene-related peptide binding monoclonal antibodies for the preventive treatment of episodic migraine - an updated systematic review and meta-analysis.
    Deng H, Li GG, Nie H, Feng YY, et al · · 2020 · cited 72× · PMID 32061264 · DOI 10.1186/s12883-020-01633-3
  5. 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
  6. The Biology of Monoclonal Antibodies: Focus on Calcitonin Gene-Related Peptide for Prophylactic Migraine Therapy.
    Raffaelli B, Reuter U. · · 2018 · cited 43× · PMID 29616494 · DOI 10.1007/s13311-018-0622-7
  7. Safety of galcanezumab in patients with episodic migraine: A randomized placebo-controlled dose-ranging Phase 2b study.
    Oakes TMM, Skljarevski V, Zhang Q, Kielbasa W, et al · · 2018 · cited 36× · PMID 29310444 · DOI 10.1177/0333102417747230
  8. Efficacy and Safety of Monoclonal Antibody Against Calcitonin Gene-Related Peptide or Its Receptor for Migraine: A Systematic Review and Network Meta-analysis.
    Wang X, Chen Y, Song J, You C. · · 2021 · cited 35× · PMID 33867991 · DOI 10.3389/fphar.2021.649143

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Other trials of Galcanezumab

Trials testing the same drug.

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Trials by the same sponsor.

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