A Study to Evaluate the Efficacy and Safety of Fremanezumab for Preventive Treatment of Migraine in Patients With Major Depressive Disorder

NCT04041284 | Completed Phase 4 Results FDA Drug

• 2 other identifiers: TV48125-MH-401422019-001989-15
• Study Type: interventional
• Target: 353
• Locations: 13 countries
• Sites: 64

Brief Summary

The primary objective is to evaluate the efficacy of monthly 225 mg sc fremanezumab in adult participants with migraine and major depressive disorder (MDD) The secondary objectives are to evaluate the efficacy of monthly 225 mg sc of fremanezumab in adult participants with migraine and MDD on the reduction of MDD symptoms, responder rates in monthly migraine days, improving quality of life, improving disability, and the safety and tolerability of monthly 225 mg sc and quarterly 675 mg sc fremanezumab in adult participants with migraine and MDD. The total duration of participant participation in the study is planned to be approximately 28 weeks.

Conditions

Migraine; Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Monthly Average Number of Migraine Days During the 12-Week DB Treatment Phase After the First Dose of Study Drug

  A migraine day was defined as when at least 1 of following situations occurred: A calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for migraine with or without aura; a calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for probable migraine (where only 1 migraine criterion was missing); a calendar day (0:00 to 23:59) demonstrating a headache of any duration that was treated with migraine-specific medications (triptans and ergot compounds); and a calendar day (00:00 to 23:59) that was immediately consecutive of any day fulfilling 3 criteria above, where participants report headache of any duration. Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over 12 week period/number of days with assessments recorded in e-diary for 12 week period)\*28. Least square (LS) mean was calculated using analysis of covariance (ANCOVA).

  Baseline (Day -28 to Day -1), up to Week 12

Secondary Outcomes (13)

• Change From Baseline in Hamilton Depression Rating Scale-17 (HAM-D 17) Items Total Score at Week 8

  Baseline, Week 8

• Number of Participants With ≥50% Reduction in Monthly Average Number of Migraine Days During the 12 Weeks After the First Dose of Study Drug

  Baseline (Day -28 to Day -1) up to Week 12

• Change From Baseline in Migraine-Specific Quality of Life (MSQoL) Questionnaire Role Function-Restrictive and Role Function-Preventive Domain Scores at Week 12

  Baseline, Week 12

• Change From Baseline in Clinical Global Impression - Severity (CGI-S) Scale Score at Weeks 4, 8, and 12

  Baseline, Weeks 4, 8, and 12

• Change From Baseline in 6-Item Headache Impact Test (HIT-6) Disability Score at Week 12

  Baseline, Week 12

Study Arms (2)

fremanezumab

EXPERIMENTAL

monthly 225 mg. In the open-label extension phase starting at week 12, all participants will receive active treatment with a quarterly dose of 675 mg sc

Drug: Fremanezumab

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Fremanezumab DRUG

Monthly 225 mg subcutaneous

Also known as: TEV-48125, LBR-101, PF-04427429, RN307

fremanezumab

Placebo DRUG

Matching Placebo

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 diagnosis of migraine with onset at ≤50 years of age.
• Prior to the screening visit 1 the participant has a 12-month history of either migraine or headache consistent with migraine
• The participant agrees not to initiate any migraine preventive during the study. Up to 30% of participants, however, may take a single such medication previously prescribed for the treatment of migraine.
• The participant has a history of major depressive disorder (MDD) at least 12 months prior to the screening visit. Participants may take a single medication prescribed for the treatment of depression as long as the dose of that medication has been stable for at least 8 weeks prior to the screening visit and expects to remain at the stable dose throughout the study.
• The participant has a body weight ≥ 45 kg and a body mass index within the range of 17.5 to 34.9 kg/m2, inclusive.
• Women of child-bearing potential whose male partners are potentially fertile (ie, no vasectomy) must use highly effective birth control methods for the duration of the study and for 6 months after discontinuation of IMP.
• Men must be sterile or, if they are potentially fertile/reproductively competent (not congenitally sterile) and their female partners are of child-bearing potential, must use a condom for the duration of the study and for 6 months after discontinuation of IMP.
• NOTE: Additional criteria apply, please contact the investigator for more information

You may not qualify if:

• The participant has failed 4 or more different medication classes to treat depression in their lifetime.
• The participant has used an intervention/device (eg, scheduled nerve blocks, implantable vagal nerve stimulation, and transcranial magnetic stimulation) for migraine or depression during the 2 months prior to screening.
• The participant has used electroconvulsive therapy at any time.
• The participant suffers from constant or nearly constant headache, defined as having headaches for more than 80% of the time he/she is awake, and less than 4 days without headache per month. Daily headache is acceptable if participant has headaches 80% or less of the time he/she is awake on most days.
• The participant has a clinical history of a severe or uncontrolled psychiatric disorder, to include the following, or at the discretion of the investigator for any clinically significant psychiatric history that would likely interfere with full participation in the study:
• The participant has a known infection or history of human immunodeficiency virus, tuberculosis, any history of Lyme disease, or chronic hepatitis B or C infection.
• The participant has a past or current history of cancer, except for appropriately treated non-melanoma skin carcinoma.
• The participant is a pregnant or nursing female or plans to become pregnant during the study, including the 6-month period after the administration of the last dose.
• The participant has a history of hypersensitivity reactions to injected proteins, including monoclonal antibodies, or a history of Stevens-Johnson Syndrome or toxic epidermal necrolysis syndrome.
• Participant has received onabotulinumtoxinA for migraine or for any medical or cosmetic reasons requiring injections in the head, face, or neck during the 3 months before screening visit.
• The participant has a history of hypersensitivity reactions to injected proteins, including monoclonal antibodies.
• The participant has participated in a clinical study of a new chemical entity or a prescription medicine within 2 months of the screening visit or 3 months in case of biologics if the half-life of the biologics is unknown or 5 half-lives, whichever is longer, or is currently participating in another study of an IMP (or a medical device).
• The participant has failed treatment (based on tolerability and/or a lack of efficacy) with any monoclonal antibodies targeting the CGRP pathway (erenumab, eptinezumab, galcanezumab, or fremanezumab) or have taken the medications within 5 half-lives of the screening visit (V1) or take them during the study.
• The participant has any clinically significant uncontrolled medical condition (treated or untreated).
• The participant has a history of alcohol or drug abuse in the opinion of the investigator.

Sponsors & Collaborators

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

Study Sites (64)

Teva Investigational Site 14330

Little Rock, Arkansas, 72205, United States

Location

Teva Investigational Site 14337

San Diego, California, 92103, United States

Location

Teva Investigational Site 14342

Denver, Colorado, 80218, United States

Location

Teva Investigational Site 14332

Stamford, Connecticut, 06905, United States

Location

Teva Investigational Site 14329

Hialeah, Florida, 33012, United States

Location

Teva Investigational Site 14334

Jacksonville, Florida, 32256, United States

Location

Teva Investigational Site 14341

Orlando, Florida, 32801, United States

Location

Teva Investigational Site 14411

Tampa, Florida, 33634, United States

Location

Teva Investigational Site 14336

Pikesville, Maryland, 21208, United States

Location

Teva Investigational Site 14331

Waltham, Massachusetts, 02451, United States

Location

Teva Investigational Site 14343

Bolivar, Missouri, 65613, United States

Location

Teva Investigational Site 14335

Brooklyn, New York, 11229, United States

Location

Teva Investigational Site 14345

The Bronx, New York, 10461, United States

Location

Teva Investigational Site 14340

Portland, Oregon, 97214, United States

Location

Teva Investigational Site 14338

Philadelphia, Pennsylvania, 19107, United States

Location

Teva Investigational Site 14333

Memphis, Tennessee, 38119, United States

Location

Teva Investigational Site 14339

Nashville, Tennessee, 37203, United States

Location

Teva Investigational Site 54190

Choceň, 565 01, Czechia

Location

Teva Investigational Site 54183

Prague, 140 59, Czechia

Location

Teva Investigational Site 54184

Prague, 160 00, Czechia

Location

Teva Investigational Site 54185

Prague, 186 00, Czechia

Location

Teva Investigational Site 54186

Rychnov nad Kněžnou, 516 01, Czechia

Location

Teva Investigational Site 40058

Kuopio, 70600, Finland

Location

Teva Investigational Site 40057

Oulu, 90220, Finland

Location

Teva Investigational Site 40056

Tampere, 33100, Finland

Location

Teva Investigational Site 40055

Turku, 20100, Finland

Location

Teva Investigational Site 35265

Bron, 69500, France

Location

Teva Investigational Site 35267

Saint-Priest-en-Jarez, 42277, France

Location

Teva Investigational Site 32736

Dresden, 01307, Germany

Location

Teva Investigational Site 32737

Essen, 45133, Germany

Location

Teva Investigational Site 32731

Essen, 45147, Germany

Location

Teva Investigational Site 32734

Leipzig, 04275, Germany

Location

Teva Investigational Site 32732

Mittweida, 09648, Germany

Location

Teva Investigational Site 32733

Westerstede, 26655, Germany

Location

Teva Investigational Site 63075

Athens, 11528, Greece

Location

Teva Investigational Site 63076

Glyfada, 166 75, Greece

Location

Teva Investigational Site 63077

Marousi, 15125, Greece

Location

Teva Investigational Site 80172

Hadera, 3810101, Israel

Location

Teva Investigational Site 80173

Holon, 5822012, Israel

Location

Teva Investigational Site 80177

Jerusalem, 9112001, Israel

Location

Teva Investigational Site 80178

Petah Tikva, 4941492, Israel

Location

Teva Investigational Site 80175

Rehovot, 7661041, Israel

Location

Teva Investigational Site 30242

Catanzaro, 88100, Italy

Location

Teva Investigational Site 30236

Florence, 50134, Italy

Location

Teva Investigational Site 30237

Milan, 20132, Italy

Location

Teva Investigational Site 30235

Pavia, 27100, Italy

Location

Teva Investigational Site 30232

Roma, 00128, Italy

Location

Teva Investigational Site 30234

Rome, 00163, Italy

Location

Teva Investigational Site 53447

Krakow, 30-539, Poland

Location

Teva Investigational Site 53445

Poznan, 60-529, Poland

Location

Teva Investigational Site 53446

Warsaw, 01-737, Poland

Location

Teva Investigational Site 53448

Wroclaw, 52-416, Poland

Location

Teva Investigational Site 50482

Moscow, 119021, Russia

Location

Teva Investigational Site 50483

Moscow, 121467, Russia

Location

Teva Investigational Site 50480

Moscow, 129128, Russia

Location

Teva Investigational Site 50481

Nizhny Novgorod, 603137, Russia

Location

Teva Investigational Site 31276

Seville, 41013, Spain

Location

Teva Investigational Site 31274

Valencia, 46026, Spain

Location

Teva Investigational Site 31272

Valladolid, 47003, Spain

Location

Teva Investigational Site 31273

Zaragoza, 50009, Spain

Location

Teva Investigational Site 58319

Kiyv, 04080, Ukraine

Location

Teva Investigational Site 58321

Odesa, 650000, Ukraine

Location

Teva Investigational Site 58320

Vinnytsia, 21018, Ukraine

Location

Teva Investigational Site 34254

London, SE1 7EH, United Kingdom

Location

Related Publications (1)

• Lipton RB, Ramirez Campos V, Roth-Ben Arie Z, Galic M, Mitsikostas D, Tassorelli C, Denysenko L, Cohen JM. Fremanezumab for the Treatment of Patients With Migraine and Comorbid Major Depressive Disorder: The UNITE Randomized Clinical Trial. JAMA Neurol. 2025 Jun 1;82(6):560-569. doi: 10.1001/jamaneurol.2025.0806.

  PMID: 40323613 DERIVED

MeSH Terms

Conditions

Migraine Disorders; Depressive Disorder, Major

Interventions

fremanezumab

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Depressive Disorder; Mood Disorders; Mental Disorders

Results Point of Contact

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

USMedInfo@tevapharm.com

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 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2019
• First Posted: August 1, 2019
• Study Start: September 13, 2019
• Primary Completion: August 31, 2022
• Study Completion: August 31, 2022
• Last Updated: October 2, 2023
• Results First Posted: October 2, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will share

Locations

RU (4); DE (6); PL (4); IT (6); GB (1); CZ (5); FI (4); FR (2); US (17); GR (3); IL (5); ES (4); UA (3)