A Study to Test if Fremanezumab Reduces Headache in Participants With Posttraumatic Headache (PTH)

NCT03347188 | Completed Phase 2 Results FDA Drug

• 1 other identifier: TV48125-CNS-20024
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 33

Brief Summary

This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the safety and efficacy of fremanezumab in adult participants aged 18 to 70 years, inclusive, for the prevention of PTH. The study will include a double-blind (DB) treatment period (12 weeks) and an open-label (OL) treatment period (12 weeks).

Conditions

Post-Traumatic Headache

Keywords

posttraumatic headache (PTH)

Outcome Measures

Primary Outcomes (1)

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

  A headache day was defined as a day when a participant reported a headache of at least moderate severity. Monthly averages were derived and normalized to 28 days equivalent by the following formula: (number of days of efficacy variable over relevant period/number of days with assessments recorded in the e-diary over the relevant period) \* 28. The change was calculated as post-baseline value - baseline value. Least square (LS) mean was calculated using analysis of covariance (ANCOVA) model with the duration of post traumatic headache history (less than 12 month since the brain injury or greater or equal to 12 month since the brain injury) and treatment as fixed effects and the baseline monthly average number of headache days of at least moderate severity as a covariate.

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

Secondary Outcomes (14)

• DB Period: Number of Participants Reaching at Least 50% Reduction From Baseline in Monthly Average Number of Headache Days of Any Severity During 12-Week Treatment With Fremanezumab

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

• DB Period: Number of Participants Reaching at Least 50% Reduction From Baseline in the Monthly Average Number of Headache Days of at Least Moderate Severity During 12-Week Treatment With Fremanezumab

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

• DB Period: Number of Participants Reaching at Least 50% Reduction From Baseline in the Monthly Average Number of Headache Days of at Least Moderate Severity During First 4-Week (Month 1), 5- to 8-Week (Month 2), and 9- to 12-Week (Month 3)

  Baseline (Day -28 to Day-1) up to Months 1, 2, and 3

• DB Period: Change From Baseline in the Number of Headache Days of At Least Moderate Severity During the First 4-Week (Month 1), 5- to 8-Week (Month 2), and 9- to 12-Week (Month 3)

  Baseline (Day -28 to Day -1), up to Months 1, 2, and 3

• DB Period: Change From Baseline in Disability Score, as Measured by the 6-Item Headache Impact Test (HIT-6) Total Score at Week 12 After the First Dose of Fremanezumab

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

Study Arms (2)

Fremanezumab

EXPERIMENTAL

Participants will receive fremanezumab 675 milligrams (mg) administered as 3 subcutaneous (SC) injections (225 mg/1.5 milliliters \[mL\] each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who complete the DB treatment period and continue into the OL treatment period will receive fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.

Drug: Fremanezumab

Placebo

PLACEBO COMPARATOR

Participants will receive placebo matching to fremanezumab administered as 3 SC injections (1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who complete the DB treatment period and continue into the OL treatment period will receive fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.

Drug: Placebo

Interventions

Fremanezumab DRUG

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

Also known as: TEV-48125

Fremanezumab

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 body weight greater than or equal to (≥) 45 kilograms (kg).
• Traumatic injury to the head has occurred, defined as a structural or functional injury resulting from the action of external forces.
• The participant has a diagnosis of PTH.
• The participant is not using preventive medications for headache.
• Women of childbearing potential whose male partners are potentially fertile (that is, no vasectomy) must use highly effective birth control methods for the duration of the study and for 30 weeks after the last study drug administration. Men must be sterile or, if they are potentially fertile or reproductively competent (that is, not surgically 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 30 weeks after the last study drug administration.
• NOTE- Additional criteria apply, please contact the investigator for more information.

You may not qualify if:

• The participant has a previous history of brain imaging showing evidence of intracerebral hemorrhage, subdural or epidural hematomas, or subarachnoid hemorrhage as a consequence of the traumatic head injury. Brain images with structurally insignificant changes, as discussed and approved by the sponsor, will be reviewed by the sponsor on a case-by-case basis.
• The participant has PTH attributed to craniotomy.
• The participant has whiplash and subsequent headache but no history of head injury or concussion.
• The participant is using analgesic medications containing opioids (including codeine) or a barbiturate on average more than 15 days per month.
• The participant has had exposure to a monoclonal antibody (mAb) targeting the calcitonin gene-related peptide (CGRP) pathway (erenumab, eptinezumab, galcanezumab, and fremanezumab) during the 6 months prior to the day of the screening visit.
• The participant is currently being treated with onabotulinumtoxinA (for example, Botox, Dysport, Xeomin) application in the head or neck or received any such injection during the 3 months prior to the screening visit.
• The participant has been implanted with any electronic devices for headache prevention during the 3 months prior to the screening visit or is currently using any implanted or externally applied stimulator or device.
• The participant has been treated with a nerve block for head and/or neck during the 3 months prior to the screening visit.
• The participant is a pregnant or lactating woman or plans to become pregnant during the study.
• NOTE- Additional criteria apply, please contact the investigator for more information.

Sponsors & Collaborators

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

Study Sites (33)

Teva Investigational Site 14065

Phoenix, Arizona, 85018, United States

Location

Teva Investigational Site 14069

Scottsdale, Arizona, 85259-5452, United States

Location

Teva Investigational Site 14048

Little Rock, Arkansas, 72205, United States

Location

Teva Investigational Site 30236

Little Rock, Arkansas, 72205, United States

Location

Teva Investigational Site 14052

Long Beach, California, 90806, United States

Location

Teva Investigational Site 14053

Los Angeles, California, 90073, United States

Location

Teva Investigational Site 14060

San Diego, California, 92161, United States

Location

Teva Investigational Site 14054

San Francisco, California, 94109, United States

Location

Teva Investigational Site 14045

Fairfield, Connecticut, 06824, United States

Location

Teva Investigational Site 14063

Miami, Florida, 33136, United States

Location

Teva Investigational Site 14041

North Miami, Florida, 33161, United States

Location

Teva Investigational Site 14056

Tampa, Florida, 33609, United States

Location

Teva Investigational Site 14057

Riverwoods, Illinois, 60015, United States

Location

Teva Investigational Site 14067

Indianapolis, Indiana, 46256, United States

Location

Teva Investigational Site 14058

Louisville, Kentucky, 40207, United States

Location

Teva Investigational Site 14061

Waltham, Massachusetts, 02451, United States

Location

Teva Investigational Site 14051

Kansas City, Missouri, 64128-2226, United States

Location

Teva Investigational Site 14043

Springfield, Missouri, 65810, United States

Location

Teva Investigational Site 14046

St Louis, Missouri, 63141, United States

Location

Teva Investigational Site 14119

Albany, New York, 12208, United States

Location

Teva Investigational Site 14229

Amherst, New York, 14226, United States

Location

Teva Investigational Site 14047

New York, New York, 10021, United States

Location

Teva Investigational Site 14118

The Bronx, New York, 10467, United States

Location

Teva Investigational Site 14114

Durham, North Carolina, 27713, United States

Location

Teva Investigational Site 14059

Salisbury, North Carolina, 28144, United States

Location

Teva Investigational Site 14049

Portland, Oregon, 97225, United States

Location

Teva Investigational Site 14064

Philadelphia, Pennsylvania, 19107, United States

Location

Teva Investigational Site 14040

Pittsburgh, Pennsylvania, 15236, United States

Location

Teva Investigational Site 14230

Nashville, Tennessee, 37203, United States

Location

Teva Investigational Site 14055

Dallas, Texas, 75390-8565, United States

Location

Teva Investigational Site 14050

Waco, Texas, 76711, United States

Location

Teva Investigational Site 14113

Spokane, Washington, 99202, United States

Location

Teva Investigational Site 14044

Morgantown, West Virginia, 26506, United States

Location

MeSH Terms

Conditions

Post-Traumatic Headache

Interventions

fremanezumab

Condition Hierarchy (Ancestors)

Headache Disorders, Secondary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

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 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: November 14, 2017
• First Posted: November 20, 2017
• Study Start: December 18, 2017
• Primary Completion: March 13, 2020
• Study Completion: June 3, 2020
• Last Updated: December 13, 2022
• Results First Posted: March 26, 2021

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (33)