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.
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.)
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
Parallel
Eptinezumab
DrugEptinezumab 300mg IV
Placebo
Other interventionControl - placebo IV
Headache frequency
Number of moderate to severe headache days between 9-12 weeks (inclusive) after intervention
Responder rate
Percentage change from baseline in the number of moderate to severe headache days, as captured by the participant's headache diary and at weekly follow-ups. At 9-12 weeks (inclusive) after treatment, those reporting a 50% reduction from baseline are considered responders.
Acute treatment utilization
The number of days in which an acute headache treatment was used, as captured daily in the participant headache diary, at baseline, and at weekly follow-ups until week 12.
Preventive treatment utilization
The utilization of preventive analgesics, as a categorical yes/no variable, will be recorded daily in the participant headache diary, at baseline and at weekly follow-ups until week 12
Headache disability
Patient-reported disability due to their headache, assessed using the Headache Impact Test (HIT-6) at baseline and during follow-ups at 4/8/12/24 weeks. Minimum score 36, maximum score 78; higher score indicates worse outcome.
Adverse events
Adverse events related to study medication
Click on the lead sponsor to view all of their trials.
This trial is not recruiting at the moment. You can still explore other options:
