Erenumab for Post-Traumatic Headache

Recruiting at 6 trial locations

Overseen By Dutchabong Shaw

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine

Disqualifiers: Moderate/severe TBI, Chronic migraine, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

404 Participants Needed

Trial Summary

What is the purpose of this trial?

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).

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your healthcare provider.

What data supports the effectiveness of the drug Erenumab for post-traumatic headache?

Erenumab has been shown to effectively reduce the frequency and intensity of migraines, as it is a drug specifically developed for migraine prevention. It works by blocking a molecule involved in migraine development, and has been successful in patients who did not respond to other migraine treatments. ^{1 2 3 4 5}

Is erenumab safe for use in humans?

Erenumab, also known as Aimovig, has been studied for migraine prevention and is generally considered safe. Common side effects include skin reactions and constipation, but no severe side effects or frequent treatment discontinuations have been reported. ^{2 3 6 7 8}

How does the drug Erenumab differ from other treatments for post-traumatic headache?

Erenumab is unique because it works by blocking a specific protein called the calcitonin gene-related peptide (CGRP) receptor, which is involved in the transmission of pain signals. This mechanism is different from other treatments that may not target this pathway, making it a novel option for managing post-traumatic headaches. ^{9 10 11 12 13}

Research Team

David L Brody, MD, PhD

Principal Investigator

Uniformed Services University of the Health Sciences

Eligibility Criteria

This trial is for military and civilian adults aged 18-50 who've had a mild traumatic brain injury (mTBI) and headache within the past week. They must have a healthcare provider, be stable geographically during the study, and able to consent. Those with moderate/severe TBI or chronic headaches prior to injury cannot join.

Inclusion Criteria

You had parathyroid hormone (PTH) levels checked in the past 7 days.

I have a doctor managing my standard care, including any needed brain scans and treatments.

I have had a mild traumatic brain injury within the last week.

Exclusion Criteria

I have chronic migraines or daily headaches since my injury.

I had a serious head injury with symptoms like unconsciousness or memory loss.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive erenumab or placebo once monthly via two subcutaneous injections at 3 time points over a 12-week period

12 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants may opt into continuation of treatment long-term

4 weeks

Treatment Details

Interventions

• Erenumab

Trial Overview The trial tests Erenumab, an injectable medication against placebo, in treating acute posttraumatic headache after mTBI. Participants will randomly receive either Erenumab or a placebo to compare effectiveness and safety.

Participant Groups

Group I: Active Drug Experimental Treatment 1 Intervention

Erenumab administered once monthly via two 70-mg subcutaneous injections at 3 time points over a 12-week period.

Group II: Placebo Placebo Group 1 Intervention

Placebo administered once monthly via two subcutaneous injections at 3 time points over a 12-week period.

Erenumab is already approved in United States, European Union for the following indications:

Approved in United States as Aimovig for:

• Prevention of migraine in adults

Approved in European Union as Aimovig for:

• Prevention of migraine in adults

Who Is Running the Clinical Trial?

Henry M. Jackson Foundation for the Advancement of Military Medicine

Lead Sponsor

Trials

103

Recruited

94,300+

Findings from Research

Erenumab significantly reduced cumulative monthly migraine pain in both episodic (946 patients) and chronic migraine (656 patients) patients compared to placebo, indicating its efficacy in managing migraine pain intensity.

In episodic migraine patients, erenumab also led to a significant decrease in average monthly pain intensity, while this effect was not statistically significant in chronic migraine patients, suggesting a stronger benefit in episodic cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduction in migraine pain intensity in patients treated with erenumab: A post hoc analysis of two pivotal randomized studies. Lipton, RB., Dodick, DW., Kudrow, D., et al.[2022]

Aimovig (erenumab-aooe) is the first drug specifically developed for the prevention of migraines, marking a significant advancement in migraine treatment.

Its unique mechanism of action sets it apart from other migraine medications, potentially offering new hope for patients seeking effective prevention strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aimovig for Migraine Prevention: The New Kid May Have Trouble Fitting in. Reinke, T.[2019]

Erenumab (AIMOVIG™) is a monoclonal antibody that targets the CGRP receptor, which plays a key role in migraine development, and has shown significant effectiveness in reducing migraine frequency in phase II and III clinical trials.

Erenumab has been approved in the US for preventing migraines in adults with at least 4 migraine days per month, indicating its efficacy and safety for chronic migraine sufferers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Erenumab: First Global Approval. Markham, A.[2019]

In a 12-week study involving 246 participants with episodic migraine who had previously failed two to four preventive treatments, erenumab demonstrated significant efficacy, with 30% of patients experiencing a 50% or greater reduction in monthly migraine days compared to 14% in the placebo group.

Erenumab was well-tolerated, showing a safety profile similar to placebo, with injection site pain being the most common side effect, affecting 6% of participants in both groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of erenumab in patients with episodic migraine in whom two-to-four previous preventive treatments were unsuccessful: a randomised, double-blind, placebo-controlled, phase 3b study. Reuter, U., Goadsby, PJ., Lanteri-Minet, M., et al.[2022]

Erenumab, a monoclonal antibody targeting calcitonin gene-related peptide receptors, has shown significant efficacy in reducing the number of monthly migraine days in both episodic and chronic migraine patients, with effects noticeable as early as the first week of treatment.

The treatment was effective for various types of migraines, including those with allodynia and menstrual migraines, and demonstrated favorable outcomes when used in combination with other preventive therapies, making it a promising option for patients who have not responded well to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Erenumab efficacy in migraine headache prophylaxis: A systematic review. Bagherzadeh-Fard, M., Amin Yazdanifar, M., Sadeghalvad, M., et al.[2023]

Erenumab, a monoclonal antibody for migraine prevention, has shown a strong safety and tolerability profile in various studies, with no severe adverse events reported and common side effects being mild, such as local skin reactions and constipation.

The review of multiple studies indicates that treatment with erenumab is well tolerated, with no significant issues leading to discontinuation, reinforcing its potential as a safe option for migraine management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability evaluation of erenumab for the preventive treatment of migraine. Deligianni, CI., Mitsikostas, DD., Ashina, M.[2021]

A study involving 204 participants with migraine showed that over 90% found the erenumab autoinjector easy to use and felt confident in self-injecting, with an average satisfaction rating of over 4.5 on a 5-point scale.

The device was also well-received in terms of size and compactness, indicating that the design of the erenumab autoinjector is user-friendly and suitable for individuals new to self-injection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient Reported Ease-of-Use with a Disposable Autoinjector in Individuals with Migraine. Mead, J., Dammerman, R., Rasmussen, S.[2022]

In a phase 2 study involving 475 Japanese patients, erenumab significantly reduced the number of monthly migraine days compared to placebo, with the most effective dose being 70 mg, which showed a reduction of 2.31 days (P < 0.001).

Erenumab also demonstrated a favorable safety profile, with the most common side effect being nasopharyngitis, occurring similarly in both the treatment and placebo groups, indicating it is a promising option for migraine prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Phase 2 Study of Erenumab for the Prevention of Episodic Migraine in Japanese Adults. Sakai, F., Takeshima, T., Tatsuoka, Y., et al.[2020]

In a study involving 23 mice with traumatic brain injury (TBI), enoxaparin (ENX) was found to significantly reduce leukocyte recruitment and cerebral edema, improving neurological recovery, similar to the effects of a monoclonal antibody targeting HMGB1.

Both ENX and the HMGB1 antibody reduced blood-brain barrier permeability and edema, but ENX also decreased lung edema, suggesting it has additional benefits beyond just blocking HMGB1 signaling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does enoxaparin interfere with HMGB1 signaling after TBI? A potential mechanism for reduced cerebral edema and neurologic recovery. Li, S., Eisenstadt, R., Kumasaka, K., et al.[2022]

In a network meta-analysis of 14 studies involving 3,456 participants, atorvastatin combined with dexamethasone (ATO+DXM) was found to be the most effective treatment for reducing recurrence in patients with chronic subdural hematoma (CSDH), significantly outperforming other interventions.

Other effective treatments included dexamethasone, tranexamic acid, and atorvastatin alone, all showing significant efficacy compared to placebo or standard neurosurgical treatment, highlighting the potential for these drug combinations in managing CSDH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness Comparisons of Drug Therapy on Chronic Subdural Hematoma Recurrence: A Bayesian Network Meta-Analysis and Systematic Review. Yu, W., Chen, W., Jiang, Y., et al.[2022]

A reproducible model of mild traumatic brain injury (mTBI) was established using a weight drop apparatus, which effectively demonstrated clinical signs of concussion, such as longer time to right (TTR) and increased hemoglobin levels in the mTBI groups.

Treatment with enoxaparin did not increase the risk of hemorrhage in the mTBI groups, suggesting that it may be safe for use in patients with mild TBI without exacerbating bleeding risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of enoxaparin administration in relationship to hemorrhage in mild traumatic brain injury. Dhir, T., Weiss, E., Wolanin, K., et al.[2019]

In a study involving 1902 patients with unstable angina (UA) or non-ST elevation myocardial infarction (NSTEMI), enoxaparin demonstrated safety and efficacy, with a composite endpoint incidence of 16.3% at 15 days, comparable to previous large-scale trials (ESSENCE and TIMI-11B).

The study reported lower rates of major (1.1%) and minor (6.6%) bleeding complications compared to the ESSENCE/TIMI-11B trials, indicating that enoxaparin is a safer option for patients, especially those aged over 75 years who showed higher bleeding rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Enoxaparin for the Treatment of Unstable Angina and Non-ST Segment Elevation Myocardial Infarction: the ENO-INT Study]. Gratsianskiĭ, NA., Alesh De Konto, A., Zuniga, MA., et al.[2018]

Early venous thromboembolic prophylaxis (VTEp) administered within 48 hours after blunt head trauma significantly reduced the risk of VTE complications in patients with combined acute subdural and subarachnoid hemorrhage, with an odds ratio of 0.468.

The timing of VTEp did not affect mortality rates or the need for delayed craniectomy, indicating that early intervention is both safe and effective in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Timing of venous thromboembolic pharmacological prophylaxis in traumatic combined subdural and subarachnoid hemorrhage. Jakob, DA., Lewis, M., Benjamin, ER., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Reduction in migraine pain intensity in patients treated with erenumab: A post hoc analysis of two pivotal randomized studies. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Aimovig for Migraine Prevention: The New Kid May Have Trouble Fitting in. [2019]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Erenumab: First Global Approval. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of erenumab in patients with episodic migraine in whom two-to-four previous preventive treatments were unsuccessful: a randomised, double-blind, placebo-controlled, phase 3b study. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Erenumab efficacy in migraine headache prophylaxis: A systematic review. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Safety and tolerability evaluation of erenumab for the preventive treatment of migraine. [2021]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Patient Reported Ease-of-Use with a Disposable Autoinjector in Individuals with Migraine. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

A Randomized Phase 2 Study of Erenumab for the Prevention of Episodic Migraine in Japanese Adults. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Does enoxaparin interfere with HMGB1 signaling after TBI? A potential mechanism for reduced cerebral edema and neurologic recovery. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Effectiveness Comparisons of Drug Therapy on Chronic Subdural Hematoma Recurrence: A Bayesian Network Meta-Analysis and Systematic Review. [2022]

11. Netherlands pubmed.ncbi.nlm.nih.gov

The impact of enoxaparin administration in relationship to hemorrhage in mild traumatic brain injury. [2019]

12. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Enoxaparin for the Treatment of Unstable Angina and Non-ST Segment Elevation Myocardial Infarction: the ENO-INT Study]. [2018]

13. United States pubmed.ncbi.nlm.nih.gov

Timing of venous thromboembolic pharmacological prophylaxis in traumatic combined subdural and subarachnoid hemorrhage. [2022]