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

• ClinicalTrials.gov Identifier: NCT05049057
• Recruitment Status: Recruiting
• First Posted: September 17, 2021
• Last Update Posted: February 22, 2024
• Sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine
• Information provided by (Responsible Party): Henry M. Jackson Foundation for the Advancement of Military Medicine

Tracking Information

• First Submitted Date: July 26, 2021
• First Posted Date: September 17, 2021
• Last Update Posted Date: February 22, 2024
• Actual Study Start Date: July 19, 2022
• Estimated Primary Completion Date: May 19, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 9, 2021)

Monthly Headache Days [ Time Frame: Week 8 to Week 12 ]

Effect of erenumab versus placebo on monthly headache days as measured by the daily headache diary

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 9, 2021)

• Monthly Headache Days [ Time Frame: Week 0 to Week 12 ]
  Effect of erenumab versus placebo on monthly headache days as measured by the daily headache diary
• Monthly Headache Days [ Time Frame: Week 0 to Week 4 ]
  Effect of erenumab versus placebo on monthly headache days as measured by the daily headache diary
• Monthly Headache Days [ Time Frame: Week 0 to Week 8 ]
  Effect of erenumab versus placebo on monthly headache days as measured by the daily headache diary
• Adverse Events [ Time Frame: Week 0 to Week 12 ]
  Number of adverse events reported in erenumab group compared to placebo
• Return to Full Duty [ Time Frame: Week 0 to Week 12 ]
  Time to return to full activity as measured by the daily headache diary
• Concomitant Medications [ Time Frame: Week 0 to Week 12 ]
  Monthly use of medications for acute headache treatment
• Headache Days [ Time Frame: Week 0 to Week 12 ]
  Monthly headache days after early acute versus late acute administration of erenumab compared to placebo
• HPFID Activity [ Time Frame: Week 0 to Week 12 ]
  Monthly impact on everyday activity scores as measured by the Headache Physical Function Impact Diary Domain 1
• HPFID Physical Impairment [ Time Frame: Week 0 to Week 12 ]
  Monthly impact on physical impairment scores as measured by the Headache Physical Function Impact Diary Domain 2
• HIT-6 [ Time Frame: Week 0 to Week 12 ]
  Change from baseline in headache impact scores as measured by the Headache Impact Test
• PHQ-9 [ Time Frame: 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.
• ISI [ Time Frame: Week 0 to Week 12 ]
  Change from baseline in insomnia scores as measured by the Insomnia Severity Index

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: September 9, 2021)

• MSQ [ Time Frame: Week 0 to Week 12 ]
  Change from baseline in quality of life scores as measured by the Migraine-specific Quality of Life Questionnaire
• ASC-12 [ Time Frame: Week 0 to Week 12 ]
  Change from baseline in frequency of allodynia symptoms as measured by the Allodynia Symptom Checklist
• ANAM [ Time Frame: Week 0 to Week 12 ]
  Change from baseline in neuropsychological functions as assessed by the Automated Neuropsychological Assessment Metrics
• Function of Time [ Time Frame: 0-24 hours, 24-72 hours, 72-144 hours ]
  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

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Treatment of Acute PTH With a CGRP Receptor mAb in Military Service Members and Civilians With mTBI
• Official Title: 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
• 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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Posttraumatic Headache
• Mild Traumatic Brain Injury

Intervention

• Drug: Erenumab 140 Mg/mL Subcutaneous Solution
  Active erenumab delivered via subcutaneous injection.
  Other Name: Aimovig
• Drug: Placebo
  Placebo delivered via subcutaneous injection.

Study Arms

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 9, 2021): 404
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 19, 2027
• Estimated Primary Completion Date: May 19, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 50 Years (Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Amy Guthrie, RN; 202-924-2729; amy.guthrie.ctr@usuhs.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05049057
• Other Study ID Numbers: CNRM-CGRP-2020
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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
• 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.

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.

• URL: http://fitbir.nih.gov/content/access-data

• Current Responsible Party: Henry M. Jackson Foundation for the Advancement of Military Medicine
• Original Responsible Party: Same as current
• Current Study Sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: David L Brody, MD, PhD; Uniformed Services University of the Health Sciences

• PRS Account: Henry M. Jackson Foundation for the Advancement of Military Medicine
• Verification Date: February 2024