A Phase 2, Multicenter, Randomized, Proof-of-Concept, Double-Blind, Placebo-Controlled, Parallel-Group Study, Including an Open-Label Period, Evaluating the Efficacy and Safety of 1 Subcutaneous Dose Regimen of Fremanezumab for the Treatment of Posttraumatic Headache (PTH)
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 87
- Locations
- 33
- Primary Endpoint
- 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
Study Overview
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).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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.
Exclusion Criteria
- •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.
Arms & Interventions
Fremanezumab
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.
Intervention: Fremanezumab (Drug)
Placebo
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.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
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
Time Frame: Baseline (Day -28 to Day -1), up to Week 12
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.
Secondary Outcomes
- 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: 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: 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)
- DB Period: Number of Participants (Responder and Non-Responder) With the Patient Global Impression of Change (PGIC) Scale at Weeks 4, 8, and 12 After the First Dose of Fremanezumab(Weeks 4, 8, and 12)
- OL Period: Number of Participants Who Did Not Complete the Study(Week 12 up to Week 24)
- OL Period: Number of Participants With TEAEs(Week 12 up to Week 24)
- DB Period: Number of Participants Who Did Not Complete the Study(Baseline (Day -28 to Day -1) up to Week 12)
- DB Period: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)(Baseline (Day -28 to -1) up to Week 12)
- DB Period: Number of Participants Who Received Concomitant Medications(Baseline (Day -28 to Day -1) up to Week 12)
- OL Period: Number of Participants Who Received Concomitant Medications(Week 12 up to Week 24)
- Number of Participants With Positive Findings on Electronic Columbia Suicide Severity Rating Scale (eC-SSRS)(Baseline (Day -28 to Day -1) up to Week 24)
- Number of Participants With Treatment-Emergent Antidrug Antibodies (ADA)(Baseline (Day -28 to Day -1) up to Week 24)