Erenumab for Post-Traumatic Headache

Recruiting at 4 trial locations

Overseen By Dani Smith

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Opioids, Barbiturates

Disqualifiers: Chronic headache, Major psychiatric disorder, Pregnancy, Breastfeeding, 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: Unknown

Duration: 9-12 weeks

112 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop your current medications, but you cannot have started or changed the dose of a headache preventive medication within 3 months before screening. It's best to discuss your specific medications with the trial team.

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 migraine headaches, as it is a drug specifically developed for migraine prevention. While it is not directly studied for post-traumatic headaches, its success in reducing migraine symptoms suggests it may have potential benefits for similar headache conditions. ^{1 2 3 4 5}

Is erenumab generally safe for humans?

Erenumab, used for migraine prevention, is generally safe and well-tolerated in humans. The most common side effects are mild skin reactions and constipation, with no severe side effects reported in studies. ^{3 4 6 7 8}

How is the drug Erenumab unique for treating 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, making it different from other treatments that may not target this pathway. ^{9 10 11 12 13}

What is the purpose of this trial?

This is a United States Department of Defense funded Focused Program study that aims to identify mechanisms and predictors for persistent of post-traumatic headache attributed to mild traumatic brain injury, and identify methods of preventing post-traumatic headache persistence. The objective of the clinical trial component of the Focused Program is to determine whether intervention with erenumab is an effective treatment for PTH attributed to mTBI.

Research Team

Todd Schwedt, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

Adults aged 18-70 with post-traumatic headache (PTH) due to mild traumatic brain injury, who have had PTH for 7-56 days and experienced an increase in moderate or severe headache days. Participants must be able to keep a headache diary and comply with study visits. Excluded are those with certain chronic headaches, recent use of specific treatments or preventive medications, unstable medical conditions, major psychiatric disorders, or women not using reliable contraception.

Inclusion Criteria

You have been diagnosed with parathyroid hormone (PTH) disorder within 7-56 days before joining the study.

I have been diagnosed with acute post-traumatic headache due to a mild head injury.

Willing and able to return for follow-up visits

Exclusion Criteria

I have recently started or changed my headache prevention medication.

You are not able to have a magnetic resonance imaging (MRI) scan due to having metal implants, certain medical devices, or other factors that could affect the quality of the MRI images.

I have not used Botox in my head, neck, or face in the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline

Participants are monitored for baseline headache frequency and characteristics

4 weeks

Treatment

Participants receive either erenumab or placebo in a double-blind, randomized, placebo-controlled setting

9-12 weeks

Regular visits for administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including follow-up questionnaires and headache diary data

4 weeks

Treatment Details

Interventions

• Erenumab
• Placebo

Trial Overview The trial is testing Erenumab against a placebo to see if it can effectively treat persistent headaches that develop after a mild traumatic brain injury. Participants will be randomly assigned to receive either the medication or placebo as part of the study's efforts to understand and prevent long-term PTH.

Participant Groups

Group I: Erenumab Experimental Treatment 1 Intervention

140 mg erenumab

Group II: Placebo Placebo Group 1 Intervention

placebo comparator

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?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Amgen

Industry Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Arizona State University

Collaborator

Trials

311

Recruited

109,000+

Phoenix VA Health Care System

Collaborator

Trials

13

Recruited

1,500+

University of Arizona

Collaborator

Trials

545

Recruited

161,000+

Translational Genomics Research Institute

Collaborator

Trials

36

Recruited

107,000+

Findings from Research

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 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]

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]

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, 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 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]

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 study of 1,660 patients with isolated acute subdural hematomas, early pharmacological venous thromboembolism prophylaxis (within 48 hours) significantly reduced the risk of VTE complications compared to late prophylaxis (after 48 hours).

Low molecular weight heparin (LMWH) was associated with lower mortality rates compared to unfractionated heparin (UH), indicating that LMWH may be a safer option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venous thromboembolic pharmacological prophylaxis in severe traumatic acute subdural hematomas: Early prophylaxis is effective and safe. Jakob, DA., Benjamin, ER., Recinos, G., et al.[2022]

Administering pharmacological venous thromboprophylaxis (VTEp) 24 to 72 hours after a traumatic brain injury (TBI) in patients with stable head CT scans is generally safe and does not lead to progression of the injury.

The review of 21 studies indicates that VTEp can be given as early as 24 hours post-injury without increasing the risk of intracranial hemorrhage, making it a viable option for preventing venous thromboembolism in TBI patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review of the Risks and Benefits of Venous Thromboembolism Prophylaxis in Traumatic Brain Injury. Margolick, J., Dandurand, C., Duncan, K., et al.[2019]

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]

References

1. 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]

2. 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]

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

Erenumab: First Global Approval. [2019]

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

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

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. 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]

10. 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]

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

Venous thromboembolic pharmacological prophylaxis in severe traumatic acute subdural hematomas: Early prophylaxis is effective and safe. [2022]

12. England pubmed.ncbi.nlm.nih.gov

A Systematic Review of the Risks and Benefits of Venous Thromboembolism Prophylaxis in Traumatic Brain Injury. [2019]

13. Netherlands pubmed.ncbi.nlm.nih.gov

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