An Efficacy and Safety Study of Fremanezumab in Adults With Migraine

NCT03308968 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: TV48125-CNS-300682017-002441-30
• Study Type: interventional
• Target: 838
• Locations: 14 countries
• Sites: 113

Brief Summary

The purpose of this study is to evaluate the efficacy, safety, and tolerability of monthly and quarterly subcutaneous (sc) injections of fremanezumab compared with sc injections of placebo in participants with chronic migraine (CM) or episodic migraine (EM) who have responded inadequately to 2 to 4 classes of prior preventive treatments. Approximately equal numbers of participants from each subgroup (CM and EM) are randomized in blinded-fashion 1:1:1 into one of 3 treatments for the subgroup - 2 active treatments and 1 placebo treatment- consisting of monthly injections for 3 months (up to Week 12). Then all participants continue into an open-label extension of 3 months (up to Week 24) during which everyone is administered sc injections of fremanezumab.

Conditions

Migraine Prophylaxis

Outcome Measures

Primary Outcomes (1)

• DB Period: Change From Baseline in Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Fremanezumab

  A migraine day was defined as when at least 1 of the 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, a migraine subtype 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). Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over relevant period/number of days with assessments recorded in e-diary over relevant period)\*28. Change was calculated as post-baseline value - baseline value.

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

Secondary Outcomes (22)

• DB Period: Percentage of Participants Reaching at Least 50 Percent (%) Reduction From Baseline in Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Fremanezumab

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

• DB Period: Change From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During the 12-Week Period After the First Dose of Fremanezumab

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

• DB Period: Change From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period After the First Dose of Fremanezumab

  Baseline (Day -28 to Day -1), up to Week 4

• DB Period: Percentage of Participants Reaching at Least 50% Reduction From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period After the First Dose of Fremanezumab

  Baseline (Day -28 to Day-1), up to Week 4

• DB Period: Change From Baseline in Monthly Average Number of Days of Use of Any Acute Headache Medications During the 12-Week Period After the First Dose of Fremanezumab

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

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Double-blind (DB) period: Participants with CM or EM will receive 3 injections of placebo 1.5 milliliters (mL) SC on Day 0 and single injection of placebo 1.5 mL SC on Days 28 and 56. Open-label (OL) period: Participants with CM or EM will receive fremanezumab (TEV-48125) 225 milligrams (mg) SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140.

Drug: Fremanezumab; Drug: Placebo

Fremanezumab Quarterly

EXPERIMENTAL

DB period: Participants with CM or EM will receive fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of placebo 1.5 mL for 2 months (on Days 28 and 56). OL period: Participants with CM or EM will receive fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140.

Drug: Fremanezumab; Drug: Placebo

Fremanezumab Monthly

EXPERIMENTAL

DB period: Participants with CM will receive fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). Participants with EM will receive fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). OL period: Participants with CM or EM will receive fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140.

Drug: Fremanezumab; Drug: Placebo

Interventions

Fremanezumab DRUG

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

Also known as: TEV-48125

Fremanezumab Monthly; Fremanezumab Quarterly; Placebo

Placebo DRUG

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

Fremanezumab Monthly; Fremanezumab Quarterly; 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.
• Body weight ≥45 kilograms.
• The participant has a history of migraine for ≥12 months prior to screening.
• 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 and the follow-up period and for 6.0 months after discontinuation of investigational medicinal product (IMP)
• Men must be sterile, or if they are potentially fertile/reproductively competent (not surgically \[that is; vasectomy\] or congenitally sterile) and their female partners are of childbearing potential, must use, together with their female partners, acceptable birth control methods for the duration of the study and for 6.0 months after discontinuation of the investigational medicinal product (IMP).
• Additional criteria apply, please contact the investigator for more information.

You may not qualify if:

• At the time of screening visit, participant is receiving any preventive migraine medications, regardless of the medical indication for more than 5 days and expects to continue with these medications.
• 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 used an intervention/device (for example; scheduled nerve blocks and transcranial magnetic stimulation) for migraine during the 2 months prior to screening.
• The participant uses triptans/ergots as preventive therapies for migraine.
• Participant uses non-steroidal anti-inflammatory drugs (NSAIDs) as preventive therapy for migraine on nearly daily basis for other indications. Note: Low dose aspirin (for example; 81 mg) used for cardiovascular disease prevention is allowed.
• Additional criteria apply, please contact the investigator for more information.

Sponsors & Collaborators

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

Study Sites (113)

Teva Investigational Site 14742

Huntsville, Alabama, 35801, United States

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Teva Investigational Site 14729

Long Beach, California, 90806, United States

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Teva Investigational Site 14739

San Diego, California, 92103, United States

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Teva Investigational Site 14843

Santa Monica, California, 90404, United States

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Teva Investigational Site 14749

Colorado Springs, Colorado, 80918, United States

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Teva Investigational Site 14758

Maitland, Florida, 32751, United States

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Teva Investigational Site 14738

Orlando, Florida, 32819, United States

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Teva Investigational Site 14760

Decatur, Georgia, 30030, United States

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Teva Investigational Site 14737

Meridian, Idaho, 83642, United States

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Teva Investigational Site 14730

Chicago, Illinois, 60607, United States

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Teva Investigational Site 14740

Evanston, Illinois, 60201, United States

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Teva Investigational Site 14735

Louisville, Kentucky, 40223, United States

Location

Teva Investigational Site 14747

Pikesville, Maryland, 21208, United States

Location

Teva Investigational Site 14750

Fall River, Massachusetts, 02720, United States

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Teva Investigational Site 14734

Watertown, Massachusetts, 02472, United States

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Teva Investigational Site 14731

Ann Arbor, Michigan, 48104, United States

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Teva Investigational Site 14748

Plymouth, Minnesota, 55441, United States

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Teva Investigational Site 14746

Omaha, Nebraska, 68114, United States

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Teva Investigational Site 14754

Berlin, New Jersey, 08009, United States

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Teva Investigational Site 14752

Albuquerque, New Mexico, 87102, United States

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Teva Investigational Site 14753

Amherst, New York, 14226, United States

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Teva Investigational Site 14736

Greensboro, North Carolina, 27405, United States

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Teva Investigational Site 14741

Greensboro, North Carolina, 27408, United States

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Teva Investigational Site 14732

Raleigh, North Carolina, 27607, United States

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Teva Investigational Site 14761

Lincoln, Rhode Island, 02865, United States

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Teva Investigational Site 14756

Warwick, Rhode Island, 02886, United States

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Teva Investigational Site 14745

Memphis, Tennessee, 38119, United States

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Teva Investigational Site 14743

Nashville, Tennessee, 37203, United States

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Teva Investigational Site 14733

Austin, Texas, 78731, United States

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Teva Investigational Site 14751

West Jordan, Utah, 84088, United States

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Teva Investigational Site 37092

Bruges, 8000, Belgium

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Teva Investigational Site 37089

Brussels, 1090, Belgium

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Teva Investigational Site 37091

Hasselt, 3500, Belgium

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Teva Investigational Site 37090

Liège, 4000, Belgium

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Teva Investigational Site 54162

Brno, 602 00, Czechia

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Teva Investigational Site 54159

Ostrava, 70200, Czechia

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Teva Investigational Site 54165

Ostrava-Moravska, 702 00, Czechia

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Teva Investigational Site 54158

Pardubice, 53002, Czechia

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Teva Investigational Site 54163

Prague, 100 00, Czechia

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Teva Investigational Site 54161

Prague, 130 00, Czechia

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Teva Investigational Site 54164

Prague, 140 59, Czechia

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Teva Investigational Site 54160

Prague, 160 00, Czechia

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Teva Investigational Site 54166

Prague, 186 00, Czechia

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Teva Investigational Site 54157

Rychnov nad Kněžnou, 51601, Czechia

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Teva Investigational Site 39051

Aalborg, 9000, Denmark

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Teva Investigational Site 39049

Aarhus, 8000, Denmark

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Teva Investigational Site 39052

Ballerup Municipality, 2750, Denmark

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Teva Investigational Site 39048

Glostrup Municipality, 2600, Denmark

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Teva Investigational Site 39050

Vejle, 7100, Denmark

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Teva Investigational Site 40034

Helsinki, 00180, Finland

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Teva Investigational Site 40035

Helsinki, 00930, Finland

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Teva Investigational Site 40036

Oulu, 90100, Finland

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Teva Investigational Site 40033

Tampere, FI-33100, Finland

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Teva Investigational Site 40032

Turku, 20100, Finland

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Teva Investigational Site 40037

Turku, 20520, Finland

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Teva Investigational Site 35237

Bron, 69677, France

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Teva Investigational Site 35238

Lille, 59037, France

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Teva Investigational Site 35235

Marseille, 13005, France

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Teva Investigational Site 35240

Nice, 06000, France

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Teva Investigational Site 35239

Strasbourg, 67098, France

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Teva Investigational Site 35236

Voiron, 38500, France

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Teva Investigational Site 32697

Berlin, 10177, Germany

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Teva Investigational Site 32690

Berlin, D-10435, Germany

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Teva Investigational Site 32694

Bochum, 44787, Germany

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Teva Investigational Site 32699

Essen, 45147, Germany

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Teva Investigational Site 32692

Göppingen, 73033, Germany

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Teva Investigational Site 32691

Halle, 06120, Germany

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Teva Investigational Site 32698

Hamburg, 20251, Germany

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Teva Investigational Site 32700

Kiel, 24149, Germany

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Teva Investigational Site 32695

Königstein im Taunus, 61462, Germany

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Teva Investigational Site 32689

München, 81377, Germany

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Teva Investigational Site 32701

Rostock, 18147, Germany

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Teva Investigational Site 32693

Ulm, 89073, Germany

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Teva Investigational Site 30199

Florence, 50134, Italy

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Teva Investigational Site 30204

Roma, 00128, Italy

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Teva Investigational Site 38126

Amsterdam, 1078VV, Netherlands

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Teva Investigational Site 38127

Blaricum, 1261 AN, Netherlands

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Teva Investigational Site 38124

Leiden, 2333 ZA, Netherlands

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Teva Investigational Site 38125

Tilburg, 5042 AD, Netherlands

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Teva Investigational Site 53420

Krakow, 31-209, Poland

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Teva Investigational Site 53425

Krakow, 33-332, Poland

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Teva Investigational Site 53422

Lodz, 90-338, Poland

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Teva Investigational Site 53424

Lodz, 90-368, Poland

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Teva Investigational Site 53418

Lublin, 20-022, Poland

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Teva Investigational Site 53416

Poznan, 60-529, Poland

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Teva Investigational Site 53419

Szczecin, 70-111, Poland

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Teva Investigational Site 53417

Warsaw, 00-909, Poland

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Teva Investigational Site 53423

Warsaw, 04-730, Poland

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Teva Investigational Site 31231

Barcelona, 08035, Spain

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Teva Investigational Site 31235

Madrid, 28223, Spain

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Teva Investigational Site 31236

Madrid, 28942, Spain

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Teva Investigational Site 31226

Pamplona, 31008, Spain

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Teva Investigational Site 31229

Santander, 39008, Spain

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Teva Investigational Site 31230

Santiago de Compostela, 15706, Spain

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Teva Investigational Site 31234

Seville, 41013, Spain

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Teva Investigational Site 31233

Valencia, 46010, Spain

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Teva Investigational Site 31227

Valencia, 46026, Spain

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Teva Investigational Site 31225

Valladolid, 47003, Spain

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Teva Investigational Site 31228

Zaragoza, 50009, Spain

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Teva Investigational Site 42050

Helsingborg, 252 20, Sweden

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Teva Investigational Site 42049

Huddinge, 141 86, Sweden

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Teva Investigational Site 42051

Lund, 260 83, Sweden

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Teva Investigational Site 42052

Stockholm, 112 81, Sweden

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Teva Investigational Site 42054

Stockholm, 114 33, Sweden

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Teva Investigational Site 45018

Bad Zurzach, 5330, Switzerland

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Teva Investigational Site 45016

Bern, 3010, Switzerland

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Teva Investigational Site 45017

Lugano, 6900, Switzerland

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Teva Investigational Site 34231

Glasgow, G51 4TF, United Kingdom

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Teva Investigational Site 34232

Hull, HU3 2JZ, United Kingdom

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Teva Investigational Site 34233

London, SE5 9NT, United Kingdom

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Teva Investigational Site 34230

Oxford, OX3 9DU, United Kingdom

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Teva Investigational Site 34235

Salford, M6 8HD, United Kingdom

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Teva Investigational Site 34236

Stoke-on-Trent, ST4 6QG, United Kingdom

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Related Publications (9)

• McAllister P, Cohen JM, Campos VR, Ning X, Janka L, Barash S. Impact of fremanezumab on disability outcomes in patients with episodic and chronic migraine: a pooled analysis of phase 3 studies. J Headache Pain. 2022 Aug 29;23(1):112. doi: 10.1186/s10194-022-01438-4.

  PMID: 36038833 DERIVED

• Diener HC, McAllister P, Jurgens TP, Kessler Y, Ning X, Cohen JM, Campos VR, Barash S, Silberstein SD. Safety and tolerability of fremanezumab in patients with episodic and chronic migraine: a pooled analysis of phase 3 studies. Cephalalgia. 2022 Jul;42(8):769-780. doi: 10.1177/03331024221076485. Epub 2022 Mar 25.

  PMID: 35331009 DERIVED

• Lampl C, Rapoport AM, Cohen JM, Barash S, Ramirez Campos V, Seminerio MJ, Ning X, Silberstein SD. Efficacy and quality-of-life improvements with fremanezumab treatment in patients with difficult-to-treat migraine with associated neurological dysfunction. Eur J Neurol. 2022 Jul;29(7):2129-2137. doi: 10.1111/ene.15328. Epub 2022 Mar 29.

  PMID: 35302681 DERIVED

• MaassenVanDenBrink A, Terwindt GM, Cohen JM, Barash S, Campos VR, Galic M, Ning X, Karppa M. Impact of age and sex on the efficacy of fremanezumab in patients with difficult-to-treat migraine: results of the randomized, placebo-controlled, phase 3b FOCUS study. J Headache Pain. 2021 Dec 18;22(1):152. doi: 10.1186/s10194-021-01336-1.

  PMID: 34922436 DERIVED

• Nahas SJ, Naegel S, Cohen JM, Ning X, Janka L, Campos VR, Krasenbaum LJ, Holle-Lee D, Kudrow D, Lampl C. Efficacy and safety of fremanezumab in clinical trial participants aged >/=60 years with episodic or chronic migraine: pooled results from 3 randomized, double-blind, placebo-controlled phase 3 studies. J Headache Pain. 2021 Nov 24;22(1):141. doi: 10.1186/s10194-021-01351-2.

  PMID: 34819017 DERIVED

• Ashina M, Cohen JM, Galic M, Campos VR, Barash S, Ning X, Kessler Y, Janka L, Diener HC. Efficacy and safety of fremanezumab in patients with episodic and chronic migraine with documented inadequate response to 2 to 4 classes of migraine preventive medications over 6 months of treatment in the phase 3b FOCUS study. J Headache Pain. 2021 Jul 10;22(1):68. doi: 10.1186/s10194-021-01279-7.

  PMID: 34246226 DERIVED

• Pazdera L, Cohen JM, Ning X, Campos VR, Yang R, Pozo-Rosich P. Fremanezumab for the Preventive Treatment of Migraine: Subgroup Analysis by Number of Prior Preventive Treatments with Inadequate Response. Cephalalgia. 2021 Sep;41(10):1075-1088. doi: 10.1177/03331024211008401. Epub 2021 May 14.

  PMID: 33990144 DERIVED

• Spierings ELH, Karppa M, Ning X, Cohen JM, Campos VR, Yang R, Reuter U. Efficacy and safety of fremanezumab in patients with migraine and inadequate response to prior preventive treatment: subgroup analyses by country of a randomized, placebo-controlled trial. J Headache Pain. 2021 Apr 16;22(1):26. doi: 10.1186/s10194-021-01232-8.

  PMID: 33863272 DERIVED

• Ferrari MD, Diener HC, Ning X, Galic M, Cohen JM, Yang R, Mueller M, Ahn AH, Schwartz YC, Grozinski-Wolff M, Janka L, Ashina M. Fremanezumab versus placebo for migraine prevention in patients with documented failure to up to four migraine preventive medication classes (FOCUS): a randomised, double-blind, placebo-controlled, phase 3b trial. Lancet. 2019 Sep 21;394(10203):1030-1040. doi: 10.1016/S0140-6736(19)31946-4. Epub 2019 Aug 16.

  PMID: 31427046 DERIVED

MeSH Terms

Interventions

fremanezumab

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
• Expanded Access: Yes

Study Record Dates

• First Submitted: October 3, 2017
• First Posted: October 13, 2017
• Study Start: October 13, 2017
• Primary Completion: October 2, 2018
• Study Completion: May 29, 2019
• Last Updated: November 9, 2021
• Results First Posted: October 9, 2019

Record last verified: 2021-11

Locations

DE (12); DK (5); NL (4); FI (6); FR (6); CZ (10); ES (11); IT (2); CH (3); US (30); BE (4); PL (9); GB (6); SE (5)