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

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02797951
• Collaborator: (none)
• Enrollment: 165
• Locations: 40
• Arm: 1
• Actual Duration (Months): 54.3
• Patients Per Site: 4.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The main purpose of this study is to assess the long-term safety and tolerability of galcanezumab administered up to once monthly in participants with episodic or chronic cluster headache who have completed study I5Q-MC-CGAL (NCT02397473) or study I5Q-MC-CGAM (NCT02438826).

Condition or Disease	Intervention/Treatment	Phase
Episodic Cluster Headache; Chronic Cluster Headache	Drug: Galcanezumab	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 165 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3b Multicenter, Single-Arm, Open-Label Safety Study of LY2951742 (Galcanezumab) in Patients With Episodic or Chronic Cluster Headache
• Actual Study Start Date: Jul 13, 2016
• Actual Primary Completion Date: Jan 21, 2021
• Actual Study Completion Date: Jan 21, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Galcanezumab Participants received 300 milligram (mg) Galcanezumab administered subcutaneously (SC) up to once a month.	Drug: Galcanezumab; Administered SC; Other Names: LY2951742

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious AEs (SAEs) [Baseline through End of Study (Up to 4 Years)]

   A TEAE is defined as the reported AEs that first occurred or worsened during the post-baseline phase compared with the baseline phase. An SAE is any adverse event from this study that results in 1 of the following: Death, initial or prolonged inpatient hospitalization, a life-threatening experience (that is, immediate risk of dying), persistent or significant disability/incapacity, congenital anomaly/birth defect, Important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the subject or may require intervention to prevent 1 of the other outcomes listed in the definition above. A summary of serious and other non-serious adverse events regardless of causality is located in the reported adverse events module.

2. Number of Participants With Suicidal Ideation and Behaviours Collected by Columbia - Suicide Severity Rating Scale (C-SSRS) [Baseline through End of Study (Up to 4 Years)]

   C-SSRS is a scale capturing occurrence, severity, and frequency of suicide-related thoughts and behaviours, and has a binary response (yes/no). Suicidal Ideation: a "yes" answer to any one of 5 suicidal ideation questions: Wish to be Dead, Non-specific Active Suicidal Thoughts, Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act, Active Suicidal Ideation with Some Intent to Act, without Specific Plan, Active Suicidal Ideation with Specific Plan and Intent. Suicidal Behaviour: a "yes" answer to any of 5 suicidal behaviour questions: Preparatory Acts or Behaviour, Aborted Attempt, Interrupted Attempt, Actual Attempt (non-fatal), Completed Suicide.

Secondary Outcome Measures

1. Number of Participants With Treatment Emergent Anti-Drug Antibodies (TE-ADA) to Galcanezumab [Baseline through End of Study (Up to 4 Years)]

   A participant is considered TE-ADA positive if: ADA "not present" baseline result and any subsequent "present" postbaseline ADA result with a titer of at least 1:20 (treatment-induced), or ADA "present" baseline result and any subsequent "present" postbaseline ADA result with a 4-fold or greater increase in titer from baseline (treatment-boosted).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participants who participated in and completed either study CGAL or study CGAM.

• Investigator judges the participant as reliable to follow all study procedures, keep all study visits, and be compliant with study requirements.

Exclusion Criteria:

• Current enrollment in or discontinuation within the last 30 days from, a clinical trial involving any investigational drug or device (with the exception of Study CGAL or Study CGAM).

• 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) (with the exception of Study CGAL or Study CGAM).

• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Hospital	Phoenix	Arizona	United States	85054
2	Stanford University Hospital	Palo Alto	California	United States	94304
3	California Medical Clinic for Headache	Santa Monica	California	United States	90404
4	Colorado Neurological Institute	Englewood	Colorado	United States	80113
5	New England Institute for Clinical Research	Stamford	Connecticut	United States	06905
6	University of South Florida	Tampa	Florida	United States	33612
7	Atlanta Center of Medical Research	Atlanta	Georgia	United States	30331
8	Michigan Head, Pain and Neurological Institute	Ann Arbor	Michigan	United States	48104
9	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
10	Clinical Trials of South Carolina	Charleston	South Carolina	United States	29406
11	Northwest Clinical Research Center	Bellevue	Washington	United States	98007-4209
12	Universitair Ziekenhuis Gent	Gent		Belgium	B-9000
13	Centre Hospitalier Regional de la Citadelle	Liege		Belgium	4000
14	Stroyan Research	Toronto	Ontario	Canada	M4S 1Y2
15	Centre de Traitement Neurologique	Montreal		Canada	H2W 1V1
16	Glostrup Hospital	Glostrup		Denmark	2600
17	Suomen Terveystalo	Jyväskylä		Finland	40100
18	Terveystalo Pulssi	Turku		Finland	20100
19	CHRU de Lille - Hôpital Roger Salengro	Lille	Cedex	France	59037
20	APHM Hôpital de la Timone	Marseille Cedex 5		France	13385
21	Hôpital de Cimiez	Nice		France	06000
22	Hopital Lariboisière	Paris		France	75475
23	CHU St Etienne Hopital Nord	Saint Etienne Cedex 2		France	42000
24	Klinikum der Universität München	München	Bayern	Germany	81377
25	Migräne- und Kopfschmerzklinik GmbH & Co. KG	Königstein	Hessen	Germany	61462
26	Praxis Dr. Philipp Stude	Bochum	Nordrhein-Westfalen	Germany	44787
27	Universitätsklinikum Jena	Jena	Thüringen	Germany	07747
28	Universitaetsklinikum Essen	Essen		Germany	45147
29	401 Army General Hospital of Athens	Athens	Attica	Greece	11525
30	Eginition Hospital of Athens	Athens		Greece	11528
31	Azienda Ospedaliera Universitaria Careggi	Firenze		Italy	50139
32	Istituto Neurologico Carlo Besta	Milano		Italy	20133
33	Fondazione Istituto Neurologico Nationale C. Mondino	Pavia		Italy	27100
34	Boerhaave Medisch Centrum	Amsterdam		Netherlands	1078 VV
35	Canisius-Wilhelmina Ziekenhuis	Nijmegen		Netherlands	6532 SZ
36	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
37	Hospital Clínico Universitario de Valencia	Valencia		Spain	46010
38	Hull Royal Infirmary	Hull	East Yorkshire	United Kingdom	HU3 2JZ
39	Walton Centre for Neurology and Neurosurgery	Liverpool	Lancashire	United Kingdom	L9 7LJ
40	Royal Stoke University Hospital	Stoke-on-Trent	Staffordshire	United Kingdom	ST4 6QG

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

• Study Protocol - May 15, 2017
• Statistical Analysis Plan - Mar 2, 2021

More Information

Additional Information:

• A Study of LY2951742 (Galcanezumab) in Participants With Cluster Headache

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT02797951
• Other Study ID Numbers: 16351; I5Q-MC-CGAR; 2015-005234-21
• First Posted: Jun 14, 2016
• Last Update Posted: Feb 10, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Eli Lilly and Company: cluster headache; headache; brain diseases; central nervous system diseases; headache disorders; headache disorders, primary; nervous system diseases; neurologic manifestations; pain; trigeminal autonomic cephalalgias
• Additional relevant MeSH terms: Cluster Headache; Headache

Study Results

Participant Flow

Recruitment Details	Participants who completed one of the parent studies I5Q-MC-CGAL (NCT02397473) or I5Q-MC-CGAM (NCT02438826) were enrolled in this study.

Arm/Group Title	Galcanezumab 300 mg SC
Arm/Group Description	Participants received 300 milligram (mg) Galcanezumab administered subcutaneously (SC) up to once a month.
Period Title: Overall Study
STARTED	165
Received at Least One Dose of Study Drug	164
COMPLETED	116
NOT COMPLETED	49

Baseline Characteristics

Arm/Group Title	Galcanezumab 300 mg SC
Arm/Group Description	Participants received 300 mg Galcanezumab administered SC up to once a month.
Overall Participants	164
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.30 (9.76)
Sex: Female, Male (Count of Participants)
Female	41 25%
Male	123 75%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	22 13.4%
Not Hispanic or Latino	117 71.3%
Unknown or Not Reported	25 15.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 0.6%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	4 2.4%
White	140 85.4%
More than one race	19 11.6%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
Belgium	17 10.4%
Canada	7 4.3%
Denmark	4 2.4%
Finland	5 3%
France	23 14%
Germany	25 15.2%
Greece	2 1.2%
Italy	24 14.6%
Netherlands	8 4.9%
Spain	17 10.4%
United Kingdom	4 2.4%
United States	28 17.1%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious AEs (SAEs)
Description	A TEAE is defined as the reported AEs that first occurred or worsened during the post-baseline phase compared with the baseline phase. An SAE is any adverse event from this study that results in 1 of the following: Death, initial or prolonged inpatient hospitalization, a life-threatening experience (that is, immediate risk of dying), persistent or significant disability/incapacity, congenital anomaly/birth defect, Important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the subject or may require intervention to prevent 1 of the other outcomes listed in the definition above. A summary of serious and other non-serious adverse events regardless of causality is located in the reported adverse events module.
Time Frame	Baseline through End of Study (Up to 4 Years)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug.

Arm/Group Title	Galcanezumab 300 mg SC
Arm/Group Description	Participants received 300 mg Galcanezumab administered SC up to once a month.
Measure Participants	164
TEAEs	119 72.6%
SAEs	17 10.4%

2. Primary Outcome

Title	Number of Participants With Suicidal Ideation and Behaviours Collected by Columbia - Suicide Severity Rating Scale (C-SSRS)
Description	C-SSRS is a scale capturing occurrence, severity, and frequency of suicide-related thoughts and behaviours, and has a binary response (yes/no). Suicidal Ideation: a "yes" answer to any one of 5 suicidal ideation questions: Wish to be Dead, Non-specific Active Suicidal Thoughts, Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act, Active Suicidal Ideation with Some Intent to Act, without Specific Plan, Active Suicidal Ideation with Specific Plan and Intent. Suicidal Behaviour: a "yes" answer to any of 5 suicidal behaviour questions: Preparatory Acts or Behaviour, Aborted Attempt, Interrupted Attempt, Actual Attempt (non-fatal), Completed Suicide.
Time Frame	Baseline through End of Study (Up to 4 Years)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug and had at least one postbaseline C-SSRS assessment.

Arm/Group Title	Galcanezumab 300 mg SC
Arm/Group Description	Participants received 300 mg Galcanezumab administered SC up to once a month.
Measure Participants	164
Suicidal Ideation	2 1.2%
Suicidal Behaviour	0 0%

3. Secondary Outcome

Title	Number of Participants With Treatment Emergent Anti-Drug Antibodies (TE-ADA) to Galcanezumab
Description	A participant is considered TE-ADA positive if: ADA "not present" baseline result and any subsequent "present" postbaseline ADA result with a titer of at least 1:20 (treatment-induced), or ADA "present" baseline result and any subsequent "present" postbaseline ADA result with a 4-fold or greater increase in titer from baseline (treatment-boosted).
Time Frame	Baseline through End of Study (Up to 4 Years)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug and had baseline and at least one post baseline ADA assessment.

Arm/Group Title	Galcanezumab 300 mg SC
Arm/Group Description	Participants received 300 mg Galcanezumab administered SC up to once a month.
Measure Participants	159
Count of Participants [Participants]	8 4.9%

Adverse Events

Time Frame	Baseline through End of Study (Up to 4 Years)
Adverse Event Reporting Description	All participants who received at least one dose of study drug.
Arm/Group Title	Galcanezumab 300 mg SC
Arm/Group Description	Participants received 300 mg Galcanezumab administered SC up to once a month.
All Cause Mortality
	Galcanezumab 300 mg SC
	Affected / at Risk (%)	# Events
Total	1/164 (0.6%)
Serious Adverse Events
	Galcanezumab 300 mg SC
	Affected / at Risk (%)	# Events
Total	17/164 (10.4%)
Gastrointestinal disorders
Constipation	1/164 (0.6%)	1
General disorders
Chest discomfort	1/164 (0.6%)	1
Immune system disorders
Sarcoidosis	1/164 (0.6%)	1
Infections and infestations
Gastroenteritis	1/164 (0.6%)	1
Injury, poisoning and procedural complications
Cartilage injury	1/164 (0.6%)	1
Exposure to household chemicals	1/164 (0.6%)	1
Rib fracture	1/164 (0.6%)	1
Tibia fracture	1/164 (0.6%)	1
Musculoskeletal and connective tissue disorders
Intervertebral disc degeneration	1/164 (0.6%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder neoplasm	1/164 (0.6%)	1
Lung adenocarcinoma	1/164 (0.6%)	1
Nervous system disorders
Cluster headache	3/164 (1.8%)	3
Sciatica	1/164 (0.6%)	1
Psychiatric disorders
Completed suicide	1/164 (0.6%)	1
Renal and urinary disorders
Ureterolithiasis	1/164 (0.6%)	1
Vascular disorders
Arterial occlusive disease	1/164 (0.6%)	1
Other (Not Including Serious) Adverse Events
	Galcanezumab 300 mg SC
	Affected / at Risk (%)	# Events
Total	62/164 (37.8%)
Infections and infestations
Bronchitis	10/164 (6.1%)	16
Influenza	16/164 (9.8%)	21
Nasopharyngitis	36/164 (22%)	46
Musculoskeletal and connective tissue disorders
Arthralgia	11/164 (6.7%)	14
Back pain	11/164 (6.7%)	13

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.