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

NCT ID: NCT04041284

Last Updated: 2023-10-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 353 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-13
• Study Completion Date: 2022-08-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

fremanezumab

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

Group Type: EXPERIMENTAL

Fremanezumab

Intervention Type: DRUG

Monthly 225 mg subcutaneous

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching Placebo

Interventions

Fremanezumab

Monthly 225 mg subcutaneous

Intervention Type: DRUG

Placebo

Matching Placebo

Intervention Type: DRUG

Other Intervention Names

TEV-48125, LBR-101, PF-04427429, RN307

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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:

• Lifetime exclusion: suicide attempt
• In the past 6 months exclusion: suicidal ideation, or other psychoactive spectrum disorders including schizoaffective disorder, delusional disorder, depression with psychotic features, and catatonic disorder.
• 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.
• The participant has evidence or medical history of psychotic symptoms as per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria such as delusions, hallucinations, or disorganized speech in the past 1 month.

NOTE: Additional criteria apply, please contact the investigator for more information

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Teva Branded Pharmaceutical Products R&D, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Teva Medical Expert, MD

Role: STUDY_DIRECTOR

Teva Branded Pharmaceutical Products R&D, Inc.

Locations

Teva Investigational Site 14330

Little Rock, Arkansas, United States

Teva Investigational Site 14337

San Diego, California, United States

Teva Investigational Site 14342

Denver, Colorado, United States

Teva Investigational Site 14332

Stamford, Connecticut, United States

Teva Investigational Site 14329

Hialeah, Florida, United States

Teva Investigational Site 14334

Jacksonville, Florida, United States

Teva Investigational Site 14341

Orlando, Florida, United States

Teva Investigational Site 14411

Tampa, Florida, United States

Teva Investigational Site 14336

Pikesville, Maryland, United States

Teva Investigational Site 14331

Waltham, Massachusetts, United States

Teva Investigational Site 14343

Bolivar, Missouri, United States

Teva Investigational Site 14335

Brooklyn, New York, United States

Teva Investigational Site 14345

The Bronx, New York, United States

Teva Investigational Site 14340

Portland, Oregon, United States

Teva Investigational Site 14338

Philadelphia, Pennsylvania, United States

Teva Investigational Site 14333

Memphis, Tennessee, United States

Teva Investigational Site 14339

Nashville, Tennessee, United States

Teva Investigational Site 54190

Choceň, , Czechia

Teva Investigational Site 54183

Prague, , Czechia

Teva Investigational Site 54184

Prague, , Czechia

Teva Investigational Site 54185

Prague, , Czechia

Teva Investigational Site 54186

Rychnov nad Kněžnou, , Czechia

Teva Investigational Site 40058

Kuopio, , Finland

Teva Investigational Site 40057

Oulu, , Finland

Teva Investigational Site 40056

Tampere, , Finland

Teva Investigational Site 40055

Turku, , Finland

Teva Investigational Site 35265

Bron, , France

Teva Investigational Site 35267

Saint-Priest-en-Jarez, , France

Teva Investigational Site 32736

Dresden, , Germany

Teva Investigational Site 32737

Essen, , Germany

Teva Investigational Site 32731

Essen, , Germany

Teva Investigational Site 32734

Leipzig, , Germany

Teva Investigational Site 32732

Mittweida, , Germany

Teva Investigational Site 32733

Westerstede, , Germany

Teva Investigational Site 63075

Athens, , Greece

Teva Investigational Site 63076

Glyfada, , Greece

Teva Investigational Site 63077

Marousi, , Greece

Teva Investigational Site 80172

Hadera, , Israel

Teva Investigational Site 80173

Holon, , Israel

Teva Investigational Site 80177

Jerusalem, , Israel

Teva Investigational Site 80178

Petah Tikva, , Israel

Teva Investigational Site 80175

Rehovot, , Israel

Teva Investigational Site 30242

Catanzaro, , Italy

Teva Investigational Site 30236

Florence, , Italy

Teva Investigational Site 30237

Milan, , Italy

Teva Investigational Site 30235

Pavia, , Italy

Teva Investigational Site 30232

Roma, , Italy

Teva Investigational Site 30234

Rome, , Italy

Teva Investigational Site 53447

Krakow, , Poland

Teva Investigational Site 53445

Poznan, , Poland

Teva Investigational Site 53446

Warsaw, , Poland

Teva Investigational Site 53448

Wroclaw, , Poland

Teva Investigational Site 50482

Moscow, , Russia

Teva Investigational Site 50483

Moscow, , Russia

Teva Investigational Site 50480

Moscow, , Russia

Teva Investigational Site 50481

Nizhny Novgorod, , Russia

Teva Investigational Site 31276

Seville, , Spain

Teva Investigational Site 31274

Valencia, , Spain

Teva Investigational Site 31272

Valladolid, , Spain

Teva Investigational Site 31273

Zaragoza, , Spain

Teva Investigational Site 58319

Kiyv, , Ukraine

Teva Investigational Site 58321

Odesa, , Ukraine

Teva Investigational Site 58320

Vinnytsia, , Ukraine

Teva Investigational Site 34254

London, , United Kingdom

Countries

United States; Czechia; Finland; France; Germany; Greece; Israel; Italy; Poland; Russia; Spain; Ukraine; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 40323613 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2019-001989-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

TV48125-MH-40142

Identifier Type: -

Identifier Source: org_study_id