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

NCT02945046 | Terminated Phase 3 Results FDA Drug

• 2 other identifiers: TV48125-CNS-300562016-003278-42
• Study Type: interventional
• Target: 169
• Locations: 12 countries
• Sites: 82

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.

Conditions

Episodic Cluster Headache

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline (Week 0), up to Week 4

Secondary Outcomes (15)

• 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

  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

  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

  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

  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

  Baseline (Week 0), up to Week 12

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Participants will receive placebo administered via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injection at Weeks 4 and 8, respectively.

Drug: Placebo

Fremanezumab 675 mg/Placebo/Placebo

EXPERIMENTAL

Participants will receive placebo as an approximately 1-hour intravenous infusion followed by fremanezumab at 675 milligrams (mg) administered as 3 subcutaneous injections (225 mg/1.5 milliliters \[mL\]) at Week 0 and placebo administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.

Drug: Fremanezumab

Fremanezumab 900/225/225 mg

EXPERIMENTAL

Participants will receive fremanezumab at 900 mg administered via an approximately 1-hour intravenous infusion followed by 3 placebo subcutaneous injections at Week 0 and fremanezumab at 225 mg administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.

Drug: Fremanezumab

Interventions

Fremanezumab DRUG

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

Also known as: TEV-48125

Fremanezumab 675 mg/Placebo/Placebo; Fremanezumab 900/225/225 mg

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.: lead

Study Sites (82)

Teva Investigational Site 13834

Phoenix, Arizona, 85018, United States

Location

Teva Investigational Site 13819

Canoga Park, California, 91303, United States

Location

Teva Investigational Site 13811

Santa Monica, California, 90404, United States

Location

Teva Investigational Site 13823

Stanford, California, 94305, United States

Location

Teva Investigational Site 13837

Aurora, Colorado, 80045, United States

Location

Teva Investigational Site 13814

Colorado Springs, Colorado, 80918, United States

Location

Teva Investigational Site 13836

Denver, Colorado, 80218, United States

Location

Teva Investigational Site 13813

Englewood, Colorado, 80113, United States

Location

Teva Investigational Site 13821

New Haven, Connecticut, 06510-2483, United States

Location

Teva Investigational Site 13812

Stamford, Connecticut, 06905, United States

Location

Teva Investigational Site 13810

Gainesville, Florida, 32607, United States

Location

Teva Investigational Site 13815

Orlando, Florida, 32806, United States

Location

Teva Investigational Site 13829

Ormond Beach, Florida, 32174, United States

Location

Teva Investigational Site 13830

St. Petersburg, Florida, 33709, United States

Location

Teva Investigational Site 13840

Tampa, Florida, 33634, United States

Location

Teva Investigational Site 13833

Columbus, Georgia, 31904, United States

Location

Teva Investigational Site 13826

Chicago, Illinois, 60614, United States

Location

Teva Investigational Site 13818

Ann Arbor, Michigan, 48104, United States

Location

Teva Investigational Site 13835

Las Vegas, Nevada, 89106, United States

Location

Teva Investigational Site 13832

Las Vegas, Nevada, 89113, United States

Location

Teva Investigational Site 13831

Lebanon, New Hampshire, 03756, United States

Location

Teva Investigational Site 13820

Princeton, New Jersey, 08540, United States

Location

Teva Investigational Site 13827

Albuquerque, New Mexico, 87102, United States

Location

Teva Investigational Site 13816

Amherst, New York, 14226, United States

Location

Teva Investigational Site 13817

New York, New York, 10019, United States

Location

Teva Investigational Site 13809

Raleigh, North Carolina, 27607, United States

Location

Teva Investigational Site 13839

Salisbury, North Carolina, 28144, United States

Location

Teva Investigational Site 13825

Cleveland, Ohio, 44195, United States

Location

Teva Investigational Site 13824

Philadelphia, Pennsylvania, 19107, United States

Location

Teva Investigational Site 13841

Richmond, Texas, 77307, United States

Location

Teva Investigational Site 13822

Virginia Beach, Virginia, 23454, United States

Location

Teva Investigational Site 78120

Auchenflower, 4066, Australia

Location

Teva Investigational Site 78118

Clayton, 3168, Australia

Location

Teva Investigational Site 78123

Melbourne, 3004, Australia

Location

Teva Investigational Site 78122

Parkville, 3050, Australia

Location

Teva Investigational Site 78121

Randwick, 2031, Australia

Location

Teva Investigational Site 11130

Calgary, T3M 1M4, Canada

Location

Teva Investigational Site 11131

Toronto, H3A 2B4, Canada

Location

Teva Investigational Site 40030

Helsinki, 00180, Finland

Location

Teva Investigational Site 40031

Oulu, 90100, Finland

Location

Teva Investigational Site 40029

Turku, 20100, Finland

Location

Teva Investigational Site 32666

Berlin, 10177, Germany

Location

Teva Investigational Site 32667

Bochum, 44787, Germany

Location

Teva Investigational Site 32660

Essen, 45147, Germany

Location

Teva Investigational Site 32665

Hamburg, 20246, Germany

Location

Teva Investigational Site 32662

Kiel, 24149, Germany

Location

Teva Investigational Site 32661

Königstein im Taunus, 61462, Germany

Location

Teva Investigational Site 32663

Rostock, 18147, Germany

Location

Teva Investigational Site 80124

Ashkelon, 7830604, Israel

Location

Teva Investigational Site 80122

Hadera, 3810101, Israel

Location

Teva Investigational Site 80125

Holon, 58100, Israel

Location

Teva Investigational Site 80121

Jerusalem, 9112001, Israel

Location

Teva Investigational Site 80123

Netanya, 4244916, Israel

Location

Teva Investigational Site 80120

Ramat Gan, 5265601, Israel

Location

Teva Investigational Site 80127

Tel Aviv, 64239, Israel

Location

Teva Investigational Site 80126

Tel Aviv, 6812509, Israel

Location

Teva Investigational Site 30190

Milan, 20133, Italy

Location

Teva Investigational Site 30192

Modena, 41124, Italy

Location

Teva Investigational Site 30194

Napoli, 80131, Italy

Location

Teva Investigational Site 30193

Pavia, 27100, Italy

Location

Teva Investigational Site 30191

Rome, 00161, Italy

Location

Teva Investigational Site 30189

Rome, 00163, Italy

Location

Teva Investigational Site 38118

Leiden, 2333 ZA, Netherlands

Location

Teva Investigational Site 38119

Nijmegen, 6532 SZ, Netherlands

Location

Teva Investigational Site 38117

Zwolle, 8025 AB, Netherlands

Location

Teva Investigational Site 53380

Bialystok, 15-402, Poland

Location

Teva Investigational Site 53383

Krakow, 31-505, Poland

Location

Teva Investigational Site 53379

Krakow, 33-332, Poland

Location

Teva Investigational Site 53382

Lodz, 90-338, Poland

Location

Teva Investigational Site 53381

Szczecin, 70-111, Poland

Location

Teva Investigational Site 31211

Galdakao, 48960, Spain

Location

Teva Investigational Site 31214

Madrid, 28034, Spain

Location

Teva Investigational Site 31213

Seville, 41013, Spain

Location

Teva Investigational Site 31212

Valladolid, 47003, Spain

Location

Teva Investigational Site 31215

Zaragoza, 50009, Spain

Location

Teva Investigational Site 42047

Huddinge, 141 86, Sweden

Location

Teva Investigational Site 42045

Vällingby, 162 68, Sweden

Location

Teva Investigational Site 34224

Glasgow, G51 4TF, United Kingdom

Location

Teva Investigational Site 34222

Liverpool, L9 7LJ, United Kingdom

Location

Teva Investigational Site 34223

London, SE1 9RT, United Kingdom

Location

Teva Investigational Site 34220

London, W6 8RF, United Kingdom

Location

Teva Investigational Site 34221

Oxford, OX3 9DU, United Kingdom

Location

MeSH Terms

Conditions

Cluster Headache

Interventions

fremanezumab

Condition Hierarchy (Ancestors)

Trigeminal Autonomic Cephalalgias; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Limitations and Caveats

Study was terminated as a result of a pre-specified futility analysis at the interim of 150 participants completing the efficacy analysis of the study.

Results Point of Contact

• Title: Director, Clinical Research
• Organization: Teva Branded Pharmaceutical Products, R&D Inc.

USMedInfo@tevapharm.com

1-888-483-8279

Study Officials

• Teva Medical Expert, MD

  Teva Branded Pharmaceutical Products R&D, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2016
• First Posted: October 26, 2016
• Study Start: January 19, 2017
• Primary Completion: May 13, 2019
• Study Completion: May 13, 2019
• Last Updated: November 9, 2021
• Results First Posted: April 13, 2020

Record last verified: 2021-11

Locations

SE (2); AU (5); FI (3); IL (8); DE (7); IT (6); PL (5); ES (5); GB (5); CA (2); US (31); NL (3)