Clinical trial NCT02945046: A Study to Evaluate the Efficacy and Safety of TEV-48125 (Fremanezumab) for the Prevention of Episodic Cluster Headache (ECH)
Official title: A Multicenter, Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, Parallel-Group Study Comparing the Efficacy and Safety of 2 Dose Regimens (Intravenous/Subcutaneous and Subcutaneous) of TEV-48125 Versus Placebo for the Prevention of Epidosic Cluster Headache
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Episodic Cluster Headache
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2016-10-26
Enrollment: 169
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a 13-week, multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel-group study to compare the efficacy and safety of 2 dose regimens of TEV-48125 (Fremanezumab) versus placebo in adult participants for the prevention of ECH.


Eligibility criteria: Inclusion Criteria:

* The participant has a history of ECH according to the International Classification of Headache Disorders - 3 beta criteria (Headache Classification Committee of the International Headache Society \[IHS\] 2013) for ≥12 months prior to screening.
* The participant has a total body weight of ≥45 kg (99 lbs.)
* The participant is in good health in the opinion of the investigator
* Women of childbearing potential (WOCBP) whose male partners are potentially fertile (that is, no vasectomy) must use highly effective birth control methods for the duration of the study.
* Men must be sterile, or if they are potentially fertile/reproductively competent (not surgically \[for example, vasectomy\] or congenitally sterile) and their female partners are of childbearing potential, must agree to use, together with their female partners, acceptable birth control for the duration of the study.
* If a participant is receiving Botox, it should be in a stable dose regimen, considered as having ≥2 cycles of Botox prior to screening. The participant should not receive Botox during the run-in period up to the evaluation period (4 weeks) where the primary endpoint is evaluated.

  * Additional criteria apply, please contact the investigator for more information

Exclusion Criteria:

* The participant has used systemic steroids for any medical reason (including treatment of the current CH cycle within ≤7 days prior to screening The participant has used an intervention/device (for example, scheduled nerve blocks) for headache during the 4 weeks prior to screening.
* The participant has clinically significant hematological, renal, endocrine, immunologic, pulmonary, gastrointestinal, genitourinary, cardiovascular, neurologic, hepatic, or ocular disease at the discretion of the investigator.
* The participant has evidence or medical history of clinically significant psychiatric issues determined at the discretion of the investigator.
* The participant has a past or current history of cancer or malignant tumor in the past 5 years, except for appropriately treated non-melanoma skin carcinoma.
* The participant is pregnant or lactating.
* The participant has a history of hypersensitivity reactions to injected proteins, including monoclonal antibodies.
* The participant has participated in a clinical study of a monoclonal antibody within 3 months or 5 half-lives before administration of the first dose of the IMP, whichever is longer, unless it is known that the participant received placebo during the study.
* The participant has a history of prior exposure to a monoclonal antibody targeting the calcitonin gene-related peptide (CGRP) pathway (AMG 334, ALD304, LY2951742, or fremanezumab). If participant has participated in a clinical study with any of these monoclonal antibodies, it has to be confirmed that the participant received placebo in order to be eligible for this study.
* The participant is an employee of the sponsor/participating study center who is directly involved in the study or is the relative of such an employee.
* The participant has an active implant for neurostimulation used in the treatment of CH.
* The participant is a member of a vulnerable population (for example, people kept in detention).
* The participant has a history of alcohol abuse prior to screening and/or drug abuse that in the investigator's opinion could interfere with the study evaluations or the participant's safety .

  * Additional criteria apply, please contact the investigator for more information

Primary outcomes:
measure: Mean Change From Baseline in the Weekly Average Number of Cluster Headache (CH) Attacks During the 4-Week Period After Administration of the First Dose of the IMP
timeFrame: Baseline (Week 0), up to Week 4
Secondary outcomes:
measure: Percentage of Participants With a ≥50% Reduction From Baseline in the Weekly Average Number of CH Attacks During the 4-Week Period After the First Dose of the IMP
timeFrame: Baseline (Week 0), up to Week 4
measure: Mean Change From Baseline in Weekly Average Number of CH Attacks During the 12-Week Period After Administration of the First Dose of the IMP
timeFrame: Baseline (Week 0), up to Week 12
measure: Mean Change From Baseline in Weekly Average Number of CH Attacks During the 4-Week Period After Administration of the Third Dose of the IMP
timeFrame: Baseline (Week 0), Week 8 up to Week 12
measure: Mean Change From Baseline in the Weekly Average Number of Days With Use of Cluster-Specific Acute Headache Medications (Triptans and Ergot Compounds) During the 12-Week Period After the First Dose of the IMP
timeFrame: Baseline (Week 0), up to Week 12
measure: Mean Change From Baseline in the Weekly Average Number of Days Oxygen Was Used to Treat Episodic Cluster Headache (ECH) During the 12-Week Period After the First Dose of the IMP
timeFrame: Baseline (Week 0), up to Week 12
measure: Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12
timeFrame: Baseline, Weeks 1, 4, 8, and 12
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Baseline up to Week 12
measure: Number of Participants With Potentially Clinically Significant Laboratory (Serum Chemistry, Hematology, and Urinalysis) Abnormal Results
timeFrame: Baseline up to Week 12
measure: Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results
timeFrame: Baseline up to Week 12
measure: Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values
timeFrame: Baseline up to Week 12
measure: Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters
timeFrame: Baseline up to Week 12
measure: Number of Participants Who Received Concomitant Medications
timeFrame: Baseline up to Week 12
measure: Number of Participants With Injection Site Reactions
timeFrame: Baseline up to Week 12
measure: Number of Participants With Hypersensitivity/Anaphylaxis Reactions
timeFrame: Baseline up to Week 12
measure: Number of Participants With Suicidal Ideation and Suicidal Behavior as Assessed by the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS)
timeFrame: Baseline up to Week 12
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Teva Investigational Site 13834
state: Arizona
city: Canoga Park
country: United States
facility: Teva Investigational Site 13819
state: California
city: Santa Monica
country: United States
facility: Teva Investigational Site 13811
state: California
city: Stanford
country: United States
facility: Teva Investigational Site 13823
state: California
city: Aurora
country: United States
facility: Teva Investigational Site 13837
state: Colorado
city: Colorado Springs
country: United States
facility: Teva Investigational Site 13814
state: Colorado
city: Denver
country: United States
facility: Teva Investigational Site 13836
state: Colorado
city: Englewood
country: United States
facility: Teva Investigational Site 13813
state: Colorado
city: New Haven
country: United States
facility: Teva Investigational Site 13821
state: Connecticut
city: Stamford
country: United States
facility: Teva Investigational Site 13812
state: Connecticut
city: Gainesville
country: United States
facility: Teva Investigational Site 13810
state: Florida
city: Orlando
country: United States
facility: Teva Investigational Site 13815
state: Florida
city: Ormond Beach
country: United States
facility: Teva Investigational Site 13829
state: Florida
city: Saint Petersburg
country: United States
facility: Teva Investigational Site 13830
state: Florida
city: Tampa
country: United States
facility: Teva Investigational Site 13840
state: Florida
city: Columbus
country: United States
facility: Teva Investigational Site 13833
state: Georgia
city: Chicago
country: United States
facility: Teva Investigational Site 13826
state: Illinois
city: Ann Arbor
country: United States
facility: Teva Investigational Site 13818
state: Michigan
city: Las Vegas
country: United States
facility: Teva Investigational Site 13835
state: Nevada
city: Las Vegas
country: United States
facility: Teva Investigational Site 13832
state: Nevada
city: Lebanon
country: United States
facility: Teva Investigational Site 13831
state: New Hampshire
city: Princeton
country: United States
facility: Teva Investigational Site 13820
state: New Jersey
city: Albuquerque
country: United States
facility: Teva Investigational Site 13827
state: New Mexico
city: Amherst
country: United States
facility: Teva Investigational Site 13816
state: New York
city: New York
country: United States
facility: Teva Investigational Site 13817
state: New York
city: Raleigh
country: United States
facility: Teva Investigational Site 13809
state: North Carolina
city: Salisbury
country: United States
facility: Teva Investigational Site 13839
state: North Carolina
city: Cleveland
country: United States
facility: Teva Investigational Site 13825
state: Ohio
city: Philadelphia
country: United States
facility: Teva Investigational Site 13824
state: Pennsylvania
city: Richmond
country: United States
facility: Teva Investigational Site 13841
state: Texas
city: Virginia Beach
country: United States
facility: Teva Investigational Site 13822
state: Virginia
city: Auchenflower
country: Australia
facility: Teva Investigational Site 78120
city: Clayton
country: Australia
facility: Teva Investigational Site 78118
city: Melbourne
country: Australia
facility: Teva Investigational Site 78123
city: Parkville
country: Australia
facility: Teva Investigational Site 78122
city: Randwick
country: Australia
facility: Teva Investigational Site 78121
city: Calgary
country: Canada
facility: Teva Investigational Site 11130
city: Toronto
country: Canada
facility: Teva Investigational Site 11131
city: Helsinki
country: Finland
facility: Teva Investigational Site 40030
city: Oulu
country: Finland
facility: Teva Investigational Site 40031
city: Turku
country: Finland
facility: Teva Investigational Site 40029
city: Berlin
country: Germany
facility: Teva Investigational Site 32666
city: Bochum
country: Germany
facility: Teva Investigational Site 32667
city: Essen
country: Germany
facility: Teva Investigational Site 32660
city: Hamburg
country: Germany
facility: Teva Investigational Site 32665
city: Kiel
country: Germany
facility: Teva Investigational Site 32662
city: Konigstein im Taunus
country: Germany
facility: Teva Investigational Site 32661
city: Rostock
country: Germany
facility: Teva Investigational Site 32663
city: Ashkelon
country: Israel
facility: Teva Investigational Site 80124
city: Hadera
country: Israel
facility: Teva Investigational Site 80122
city: Holon
country: Israel
facility: Teva Investigational Site 80125
city: Jerusalem
country: Israel
facility: Teva Investigational Site 80121
city: Netanya
country: Israel
facility: Teva Investigational Site 80123
city: Ramat Gan
country: Israel
facility: Teva Investigational Site 80120
city: Tel Aviv
country: Israel
facility: Teva Investigational Site 80127
city: Tel-Aviv
country: Israel
facility: Teva Investigational Site 80126
city: Milan
country: Italy
facility: Teva Investigational Site 30190
city: Modena
country: Italy
facility: Teva Investigational Site 30192
city: Napoli
country: Italy
facility: Teva Investigational Site 30194
city: Pavia
country: Italy
facility: Teva Investigational Site 30193
city: Rome
country: Italy
facility: Teva Investigational Site 30191
city: Rome
country: Italy
facility: Teva Investigational Site 30189
city: Leiden
country: Netherlands
facility: Teva Investigational Site 38118
city: Nijmegen
country: Netherlands
facility: Teva Investigational Site 38119
city: Zwolle
country: Netherlands
facility: Teva Investigational Site 38117
city: Bialystok
country: Poland
facility: Teva Investigational Site 53380
city: Krakow
country: Poland
facility: Teva Investigational Site 53383
city: Krakow
country: Poland
facility: Teva Investigational Site 53379
city: Lodz
country: Poland
facility: Teva Investigational Site 53382
city: Szczecin
country: Poland
facility: Teva Investigational Site 53381
city: Galdakao.
country: Spain
facility: Teva Investigational Site 31211
city: Madrid
country: Spain
facility: Teva Investigational Site 31214
city: Sevilla
country: Spain
facility: Teva Investigational Site 31213
city: Valladolid
country: Spain
facility: Teva Investigational Site 31212
city: Zaragoza
country: Spain
facility: Teva Investigational Site 31215
city: Huddinge
country: Sweden
facility: Teva Investigational Site 42047
city: Vallingby
country: Sweden
facility: Teva Investigational Site 42045
city: Glasgow
country: United Kingdom
facility: Teva Investigational Site 34224
city: Liverpool
country: United Kingdom
facility: Teva Investigational Site 34222
city: London
country: United Kingdom
facility: Teva Investigational Site 34223
city: London
country: United Kingdom
facility: Teva Investigational Site 34220
city: Oxford
country: United Kingdom
facility: Teva Investigational Site 34221
Study officials:
affiliation: Teva Branded Pharmaceutical Products R&D, Inc.
name: Teva Medical Expert, MD
role: STUDY_DIRECTOR
References: