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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Mild Traumatic Brain Injury; Posttraumatic Headache
• Intervention / Treatment: Drug: Erenumab 140 Mg/mL Subcutaneous Solution; Drug: Placebo

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 Type: Interventional
• Enrollment (Estimated): 404
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Amy Guthrie, RN; Phone Number: 202-924-2729; Email: amy.guthrie.ctr@usuhs.edu

Study Locations

• United States
  • North Carolina
    • Fort Bragg, North Carolina, United States, 28310
      • Recruiting
      • Womack Army Medical Center - Fort Liberty
      • Contact: Jennifer Robles, RN; Phone Number: 240-749-1042; Email: jennifer.robles.ctr@usuhs.edu
      • Contact: Alexandra Fraiser; Phone Number: 240-749-4550; Email: alexandra.fraiser.ctr@usuhs.edu
      • Principal Investigator: CDR Katherine Demers
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15203
      • Not yet recruiting
      • University of Pittsburgh Concussion Research Laboratory
      • Contact: Courtney Perry; Phone Number: 412-904-1298; Email: cap236@pitt.edu
      • Principal Investigator: Anthony Kontos, MD
  • Texas
    • El Paso, Texas, United States, 79918
      • Recruiting
      • William Beaumont Army Medical Center
      • Contact: Cecilia Valdovinos, NP; Email: cecilia.valdovinos.ctr@usuhs.edu
      • Principal Investigator: Sean Sebesta, MD
  • Washington
    • Tacoma, Washington, United States, 98431
      • Not yet recruiting
      • Madigan Army Medical Center
      • Contact: Janel Cuevas; Phone Number: 240-890-6518; Email: janel.cuevas.ctr@usuhs.edu
      • Principal Investigator: Melissa Belle, NP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

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:

  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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active Drug; 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; Active erenumab delivered via subcutaneous injection.; Other Names: Aimovig
Placebo Comparator: Placebo; Placebo administered once monthly via two subcutaneous injections at 3 time points over a 12-week period.	Drug: Placebo; Placebo delivered via subcutaneous injection.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
MSQ	Change from baseline in quality of life scores as measured by the Migraine-specific Quality of Life Questionnaire	Week 0 to Week 12
ASC-12	Change from baseline in frequency of allodynia symptoms as measured by the Allodynia Symptom Checklist	Week 0 to Week 12
ANAM	Change from baseline in neuropsychological functions as assessed by the Automated Neuropsychological Assessment Metrics	Week 0 to Week 12
Function of Time	Effect of erenumab compared to placebo as a function of time from mTBI to first dose of erenumab as measured by the daily headache diary	0-24 hours, 24-72 hours, 72-144 hours

Collaborators and Investigators

• Sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine
• Investigators: Principal Investigator: David L Brody, MD, PhD, Uniformed Services University of the Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2022
• Primary Completion (Estimated): May 19, 2026
• Study Completion (Estimated): May 19, 2027

Study Registration Dates

• First Submitted: July 26, 2021
• First Submitted That Met QC Criteria: September 9, 2021
• First Posted (Actual): September 17, 2021

Study Record Updates

• Last Update Posted (Actual): February 22, 2024
• Last Update Submitted That Met QC Criteria: February 21, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Headache Disorders; Head Injuries, Closed; Wounds, Nonpenetrating; Headache Disorders, Secondary; Brain Injuries; Brain Injuries, Traumatic; Headache; Brain Concussion; Post-Traumatic Headache; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Calcitonin Gene-Related Peptide Receptor Antagonists; Erenumab
• Other Study ID Numbers: CNRM-CGRP-2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Identifier-free participant data sets will be shared with the Uniformed Services University Center for Neuroscience and Regenerative Medicine Data Repository. Identifier-free data sets may also be shared with the Federal Interagency Traumatic Brain Injury Research (FITBIR) Data Repository
• IPD Sharing Time Frame: After study completion, data sets will be de-identified and shared with the repositories. De-identified data sets will be stored in the repositories indefinitely.

IPD Sharing Access Criteria

Access to the CNRM Data Repository will be determined b the CNRM Data Quality, Access, and Publication Committee. Investigators requesting access to the data will provide a list of investigators and collaborators who will have access to the data, documentation of Ethical Conduct of Research and Human Participants Protection Training, and documentation of Institutional Review Board Approval of the research project.

Access to FITBIR will follow FITBIR Access Criteria.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No