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

Phase 2

Recruiting

• Conditions: Posttraumatic Headache; Mild Traumatic Brain Injury
• Interventions: Drug: Placebo; Drug: Erenumab 140 Mg/mL Subcutaneous Solution

• Registration Number: NCT05049057
• Lead Sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2021-07-26
• Study First Submitted QC: 2021-09-09
• Study First Posted: 2021-09-17
• Study Start: 2022-07-19
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-21
• Last Update Posted: 2024-02-22
• Primary Completion: 2026-05-19
• Study Completion: 2027-05-19

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 404

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

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Exclusion Criteria

• Sustained a moderate or severe TBI, rather than mTBI, indicated with at least 1 of the following associated with head injury:

  1. abnormal structural imaging
  2. loss of consciousness for >30 minutes
  3. 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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo administered once monthly via two subcutaneous injections at 3 time points over a 12-week period.
Active Drug	Erenumab 140 Mg/mL Subcutaneous Solution	Erenumab administered once monthly via two 70-mg subcutaneous injections at 3 time points over a 12-week period.

Primary Outcome Measures

Name	Time	Method
Monthly Headache Days	Week 8 to Week 12	Effect of erenumab versus placebo on monthly headache days as measured by the daily headache diary

Secondary Outcome Measures

Name	Time	Method
HPFID Activity	Week 0 to Week 12	Monthly impact on everyday activity scores as measured by the Headache Physical Function Impact Diary Domain 1
Monthly Headache Days	Week 0 to Week 8	Effect of erenumab versus placebo on monthly headache days as measured by the daily headache diary
Adverse Events	Week 0 to Week 12	Number of adverse events reported in erenumab group compared to placebo
HPFID Physical Impairment	Week 0 to Week 12	Monthly impact on physical impairment scores as measured by the Headache Physical Function Impact Diary Domain 2
PHQ-9	Week 0 to Week 12	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.
Concomitant Medications	Week 0 to Week 12	Monthly use of medications for acute headache treatment
Return to Full Duty	Week 0 to Week 12	Time to return to full activity as measured by the daily headache diary
Headache Days	Week 0 to Week 12	Monthly headache days after early acute versus late acute administration of erenumab compared to placebo
HIT-6	Week 0 to Week 12	Change from baseline in headache impact scores as measured by the Headache Impact Test
ISI	Week 0 to Week 12	Change from baseline in insomnia scores as measured by the Insomnia Severity Index

Trial Locations

Locations (4)

Womack Army Medical Center - Fort Liberty; 🇺🇸 Fort Bragg, North Carolina, United States

University of Pittsburgh Concussion Research Laboratory; 🇺🇸 Pittsburgh, Pennsylvania, United States

William Beaumont Army Medical Center; 🇺🇸 El Paso, Texas, United States

Madigan Army Medical Center; 🇺🇸 Tacoma, Washington, United States