A Study to Evaluate the Efficacy and Safety of TEV-48125 (Fremanezumab) for the Prevention of Episodic Cluster Headache (ECH)

Phase 3TerminatedNCT02945046

Teva Branded Pharmaceutical Products R&D, Inc.169 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

169

Conditions

Episodic Cluster Headache

Interventions

FremanezumabDRUG

Fremanezumab will be administered per dose and schedule specified in the arm.

PlaceboDRUG

Placebo matching to fremanezumab will be administered per schedule specified in the arm.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

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

Locations (82)

Outcomes

Primary Outcomes

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

A CH attack was defined as a severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15 to 180 minutes with either or both of the following 2 categories: 1) at least 1 of the following symptoms or signs, ipsilateral to the headache: -conjunctival injection and/or lacrimation; -nasal congestion and/or rhinorrhea; -eyelid edema; -forehead and facial sweating; -forehead and facial flushing; -sensation of fullness in the ear; -miosis and/or ptosis. 2) a sense of restlessness or agitation. Least Squares (LS) mean calculated using analysis of covariance (ANCOVA) model with baseline preventive medication use (yes or no), sex, region (United States \[US\]/Canada or other), and treatment as fixed effects and the baseline number of CH attacks as a covariate. Change from baseline in the overall weekly average number of CH attacks during the 4-week period after administration of the first dose of study drug (based on Week 0 to 4 data) is reported.

Time frame: Baseline (Week 0), up to Week 4

Secondary Outcomes

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

Time frame: Baseline (Week 0), up to Week 4

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

A CH attack was defined as a severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15 to 180 minutes with either or both of the following 2 categories: 1) at least 1 of the following symptoms or signs, ipsilateral to the headache: -conjunctival injection and/or lacrimation; -nasal congestion and/or rhinorrhea; -eyelid edema; -forehead and facial sweating; -forehead and facial flushing; -sensation of fullness in the ear; -miosis and/or ptosis. 2) a sense of restlessness or agitation. LS mean calculated using mixed model for repeated measures (MMRM) with baseline preventive medication use (yes or no), gender, region (US/Canada or other), treatment, month, and month-by-treatment interaction as fixed effects and baseline number of CH attacks as a covariate. Change from baseline in the overall weekly average number of CH attacks during the 12-week period after administration of the first dose of study drug (based on Week 0 to 12 data) is reported.

Data from ClinicalTrials.gov

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Teva Investigational Site 13834

Phoenix, Arizona, United States

Teva Investigational Site 13819

Canoga Park, California, United States

Teva Investigational Site 13811

Santa Monica, California, United States

Teva Investigational Site 13823

Stanford, California, United States

Teva Investigational Site 13837

Aurora, Colorado, United States

Teva Investigational Site 13814

Colorado Springs, Colorado, United States

Teva Investigational Site 13836

Denver, Colorado, United States

Teva Investigational Site 13813

Englewood, Colorado, United States

Teva Investigational Site 13821

New Haven, Connecticut, United States

Teva Investigational Site 13812

Stamford, Connecticut, United States

...and 72 more locations

Time frame: Baseline (Week 0), up to Week 12

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

A CH attack was defined as a severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15 to 180 minutes with either or both of the following 2 categories: 1) at least 1 of the following symptoms or signs, ipsilateral to the headache: -conjunctival injection and/or lacrimation; -nasal congestion and/or rhinorrhea; -eyelid edema; -forehead and facial sweating; -forehead and facial flushing; -sensation of fullness in the ear; -miosis and/or ptosis. 2) a sense of restlessness or agitation. LS mean calculated using MMRM with baseline preventive medication use (yes or no), gender, region (US/Canada or other), treatment, month, and month-by-treatment interaction as fixed effects and baseline number of CH attacks as a covariate. Change from baseline in the overall weekly average number of CH attacks during the 4-week period after administration of the first dose of study drug (based on Week 8 to 12 data) is reported.

Time frame: Baseline (Week 0), Week 8 up to Week 12

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

A maximum of 2 concomitant preventive medications for CH were allowed during the study. Participants must have been on a stable dose and regimen of the concomitant medication for at least 2 weeks before screening and throughout the study. LS mean calculated using ANCOVA model with baseline preventive medication use (yes or no), gender, region (US/Canada or other), and treatment as fixed effects and the baseline number of cluster headache attacks as a covariate. Baseline data and the mean change from baseline in the overall weekly average number of days with the use of cluster-specific acute headache medications (triptans and ergot compounds) during the 12-week period after administration of the first dose of study drug (based on Week 0 to 12 data) is reported.

Time frame: Baseline (Week 0), up to Week 12

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

LS mean calculated using ANCOVA model with baseline preventive medication use (yes or no), gender, region (US/Canada or other), and treatment as fixed effects and the baseline number of cluster headache attacks as a covariate. Baseline data and the mean change from baseline in the overall weekly average number of days oxygen was used to treat ECH during the 12-week period after administration of the first dose of IMP (based on Week 0 to 12 data) is reported.

Time frame: Baseline (Week 0), up to Week 12

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

The PPSI assessment was developed to measure pain intensity and was adjusted for CH symptoms improvement. Participants marked the level of CH-associated pain and indicated if pain is "1=much worse," "2=moderately worse," "3=slightly worse," "4=unchanged," "5=slightly improved," "6=moderately improved," or "7=much improved" compared with 4 weeks prior. PPSI was defined as the change in pain that corresponds with a minimal rating of "5=slightly improved." Data at Week 1 was recorded on Day 7 in the electronic diary device at home. Week 12 data also included assessment at the early withdrawal visit for participants who discontinued the study early.

Time frame: Baseline, Weeks 1, 4, 8, and 12

Number of Participants With Adverse Events (AEs)

An AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Relationship of AE to treatment was determined by the Investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent the previously listed serious outcomes. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.