Treatment of Acute PTH With a CGRP Receptor mAb in Military Service Members and Civilians With mTBI

Study Overview
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Brief Summary
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This study aims to assess the effect and safety of erenumab compared to placebo for the treatment of acute posttraumatic headache (PTH) in military service members and civilians with mild traumatic brain injury (mTBI).

Detailed Description
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Headache is recognized as one of the most common and disabling symptoms following head trauma. This study is designed to assess a calcitonin gene-related peptide (cGRP) monoclonal antibody (erenumab) for the preventive treatment of PTH based on the rationale that headache posttrauma is similar to migraine and is mediated by the activation of the trigeminal vascular system and subsequent release of cGRP. This study is a randomized, double-blind, placebo-controlled study to assess the safety, tolerability, and efficacy of erenumab 140 mg for the treatment of PTH in military service members and civilians with mTBI at military treatment facilities across the United States.

Official Title
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Treatment of Acute Post-Traumatic Headache With Erenumab 140 mg, Military Service Members and Civilians With Mild TBI: A Randomized, Double Blind, Placebo Controlled, Multicenter 12-week Duration Study Followed by a 4-week Open-Label Safety Extension

Conditions
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Posttraumatic Headache, Mild Traumatic Brain Injury

Intervention / Treatment
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* Drug: Erenumab 140 Mg/mL Subcutaneous Solution
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥18 and ≤50 years of age mTBI from any cause including impact, rotational acceleration, blast, or a combination, has occurred within the prior 7 days PTH has occurred within the prior 7 days Able to provide informed consent Likely to stay in the same geographical area for the duration of study Has a personal health care provider for standard of care PTH and TBI, including education, diagnostic procedures including neuroimaging and treatment, as deemed clinically indicated by the health care provider Exclusion Criteria: Sustained a moderate or severe TBI, rather than mTBI, indicated with at least 1 of the following associated with head injury: abnormal structural imaging loss of consciousness for >30 minutes alteration of consciousness/mental state for >24 hours 3. post-traumatic amnesia for >1 day Participants with ongoing chronic migraine or other chronic daily headache disorders at the time of injury

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active Drug<br>Erenumab administered once monthly via two 70-mg subcutaneous injections at 3 time points over a 12-week period. | Drug: Erenumab 140 Mg/mL Subcutaneous Solution<br>* Active erenumab delivered via subcutaneous injection.<br>* Other names: Aimovig;|
| Placebo Comparator: Placebo<br>Placebo administered once monthly via two subcutaneous injections at 3 time points over a 12-week period. | Drug: Placebo<br>* Placebo delivered via subcutaneous injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Monthly Headache Days | Effect of erenumab versus placebo on monthly headache days as measured by the daily headache diary | Week 8 to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Monthly Headache Days | Effect of erenumab versus placebo on monthly headache days as measured by the daily headache diary | Week 0 to Week 12 | 
| Monthly Headache Days | Effect of erenumab versus placebo on monthly headache days as measured by the daily headache diary | Week 0 to Week 4 | 
| Monthly Headache Days | Effect of erenumab versus placebo on monthly headache days as measured by the daily headache diary | Week 0 to Week 8 | 
| Adverse Events | Number of adverse events reported in erenumab group compared to placebo | Week 0 to Week 12 | 
| Return to Full Duty | Time to return to full activity as measured by the daily headache diary | Week 0 to Week 12 | 
| Concomitant Medications | Monthly use of medications for acute headache treatment | Week 0 to Week 12 | 
| Headache Days | Monthly headache days after early acute versus late acute administration of erenumab compared to placebo | Week 0 to Week 12 | 
| HPFID Activity | Monthly impact on everyday activity scores as measured by the Headache Physical Function Impact Diary Domain 1 | Week 0 to Week 12 | 
| HPFID Physical Impairment | Monthly impact on physical impairment scores as measured by the Headache Physical Function Impact Diary Domain 2 | Week 0 to Week 12 | 
| HIT-6 | Change from baseline in headache impact scores as measured by the Headache Impact Test | Week 0 to Week 12 | 
| PHQ-9 | Change from baseline in depressive symptoms after mTBI as measured by the self-report questionnaire, Patient Health Questionnaire-9, Total Score. Total scores range from a minimum of 0 to a maximum of 27, which are rated from minimal to severe levels of depression. | Week 0 to Week 12 | 
| ISI | Change from baseline in insomnia scores as measured by the Insomnia Severity Index | Week 0 to Week 12 |