Eary Infusion of Eptinezumab for TreatmEnt of ACute Post-Traumatic Headaches (ELITE-ACT)

NCT07191145 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: 6558
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Most individuals with mild traumatic brain injury (mTBI) experience post-traumatic headaches (PTH). Of PTH, 50% present with a migraine phenotype which is the most disabling type of PTH. Patients with migraine-PTH are at greater risk of persistent symptoms whereby the acute PTH (aPTH) becomes persistent PTH (pPTH) (ie. lasting \> 3 months) with a conversion rate of 47-95%. As migraine symptoms become chronic, it becomes treatment resistant. Despite these implications, early preventive medication management of PTH is marred by lengthy trials of multiple medications (2-3 months for each) and adverse effects that aggravate mTBI symptoms (fatigue, nausea, and presyncope). There is a compelling need to establish an effective treatment to prevent this debilitating outcome. Eptinezumab is a calcitonin gene-related peptide (CGRP)-blocking monoclonal antibody that reduces migraine burden in patients with migraines after a single infusion. Patients with PTH have higher serum levels of CGRP and experimental infusion of CGRP to patients with mTBI reproduces migraine PTH symptoms. Given the similarly in CGRP expression between chronic migraines and PTH, an infusion of eptinezumab within 8 weeks of PTH is hypothesized to reduce headache burden 3 months after treatment and prevent pPTH.

Conditions

Post Traumatic Headache

Keywords

Migraine

Outcome Measures

Primary Outcomes (1)

• Headache frequency

  Number of moderate to severe headache days between 9-12 weeks (inclusive) after intervention

  9-12 weeks (inclusive) after intervention

Secondary Outcomes (10)

• Responder rate

  At 9-12 weeks (inclusive) after treatment, those reporting a 50% reduction from baseline are considered responders.

• Acute treatment utilization

  Daily until 12 weeks

• Preventive treatment utilization

  Daily until 12 weeks

• Headache disability

  Baseline until 12 weeks

• Concussion severity

  Baseline until 12 weeks

Other Outcomes (1)

• Adverse events

  Baseline until until 24 weeks after treatment

Study Arms (2)

Intervention - Eptinezumab

EXPERIMENTAL

Eptinezumab 300mg IV once within 8 weeks of post-traumatic headache onset

Drug: Eptinezumab

Control - Placebo

PLACEBO COMPARATOR

Placebo IV once within 8 weeks of post-traumatic headache onset

Other: Placebo

Interventions

Eptinezumab DRUG

Eptinezumab 300mg IV

Intervention - Eptinezumab

Placebo OTHER

Control - placebo IV

Control - Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Meet diagnostic criteria for acute post-traumatic headache as per ICHD-3 criteria
• Meet migraine screening questionnaire criteria (MSQ score ≥ 4) during at least one of the weekly screening calls
• Within 8 weeks after onset of PTH
• Negative human chorionic gonadotropin test before treatment, for female participants of childbearing potential who are not practicing medically appropriate methods of birth control (e.g., hormonal contraceptives, implants, injectables, intrauterine devices, intrauterine systems, etc.)

You may not qualify if:

• Diagnosis of moderate to severe TBI
• History of mTBI within the past 5 years
• Pre-existing chronic migraine and its subtypes, tension-type headache, trigeminal autonomic cephalalgias, cranial neuralgias, daily headache, diagnosis of another secondary headache disorder per ICHD-3 (except medication overuse headache)
• Concurrent use of CGRP-related treatment or botulinum toxin within the last three month for migraine
• Substance / opioids use disorder
• Confounding chronic pain disorder / clinically significant pains
• Concurrent major injuries (long bone, rib, and spinal fractures) or surgical intervention while in hospital on initial trauma
• On-going litigation for current trauma
• Pregnancy/breast-feeding
• Uncontrolled psychiatric conditions (depression, PTSD, anxiety, functional neurological disorder)
• Use of opioids/barbiturates for headaches (\> 4 days/month)
• Hereditary fructose intolerance

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead

Study Sites (1)

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

MeSH Terms

Conditions

Post-Traumatic Headache; Migraine Disorders

Interventions

eptinezumab

Condition Hierarchy (Ancestors)

Headache Disorders, Secondary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary

Study Officials

• Howard Meng, MD

  Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Howard Meng, MD

CONTACT

416-480-4864; howard.meng@sunnybrook.ca

Lavarnan Sivanathan, MD

CONTACT

lavarnan.sivanathan@sunnybrook.ca

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Group 1: Intervention - Eptinzumab 300mg IV once within 8 weeks of PTH onset Group 2: Control - Placebo once within 8 weeks of PTH onset

Study Record Dates

• First Submitted: September 5, 2025
• First Posted: September 24, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: December 29, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Upon publication, no limit on time
• Access Criteria: Contact study investigators

Locations

CA (1)