Erenumab for Pediatric Migraine

(OASIS(EM) Trial)

Recruiting at 78 trial locations

Overseen By Amgen Call Center

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Amgen

Must not be taking: Ergotamines, Triptans, Opioids, others

Disqualifiers: Cluster headache, Hemiplegic migraine, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 1

456 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it mentions that certain medications and treatments are prohibited before and during the baseline phase. It's best to discuss your current medications with the study team to see if they are allowed.

What data supports the effectiveness of the drug Erenumab for preventing migraines?

Erenumab has been shown to significantly reduce the number of migraine days in both episodic and chronic migraine patients, and it is approved for migraine prevention in adults. It works by blocking a molecule involved in migraine development, leading to fewer migraines. ^{1 2 3 4 5}

Is erenumab safe for use in humans?

Erenumab has been shown to be generally safe and well-tolerated in adults for migraine prevention, with the most common side effects being skin reactions and constipation. No severe side effects or frequent discontinuations due to side effects were reported in the studies reviewed. ^{2 3 5 6 7}

How is the drug Erenumab unique for treating pediatric migraine?

Erenumab is unique because it works by blocking a protein called calcitonin gene-related peptide (CGRP), which is involved in migraine attacks. This mechanism is different from other migraine treatments, which often focus on relieving symptoms rather than preventing them. ^{8 9 10 11 12}

What is the purpose of this trial?

This study will evaluate the efficacy and safety of erenumab in migraine prevention in children (6 to \<12 years) and adolescents (12 to \<18 years) with episodic migraine. The study hypothesis is that in pediatric participants with episodic migraine, the combined erenumab dose group has a greater reduction from baseline to week 9 through week 12 (month 3) in monthly migraine days (MMDs) when compared with placebo in the double-blind treatment phase (DBTP).

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

This trial is for children (6-11 years) and adolescents (12-17 years) with episodic migraines, occurring 4 to less than 15 days per month. Participants must have a history of migraine for at least one year and be able to follow the study's diary requirements. They can't join if they've had certain types of headaches, no response to more than two preventive medications, substance abuse issues, significant neurological disorders other than migraine, or are using excluded treatments.

Inclusion Criteria

I have had migraines for at least 12 months.

I have had 4 to 14 migraines in the last month.

Demonstrated at least 80% compliance with the eDiary based on the last 28 days of the baseline period, if greater than 28 days in duration (eg, completing eDiary items for at least 23 out of the last 28 days of the baseline phase).

Exclusion Criteria

You have a serious mental health condition like schizophrenia, bipolar disorder, or severe depression.

I have not received botulinum toxin in my head or neck in the last 4 months.

I have taken CGRP pathway medication in the last 4 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

3 weeks

1 visit (in-person)

Prospective Baseline

Participants undergo a 4-week baseline phase to establish migraine frequency

4 weeks

Double-blind Treatment Phase (DBTP)

Participants receive placebo or Erenumab dose based on body weight via subcutaneous injection once a month

24 weeks for Group 1, 12 weeks for Group 2

Monthly visits (in-person)

Dose Level Blinded Extension

All participants receive Erenumab dose 1, dose 2, or dose 3

40 weeks

Safety Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• Erenumab

Trial Overview The trial tests different doses of Erenumab against a placebo in preventing migraines in young patients. The goal is to see if Erenumab reduces the number of monthly migraine days over three months compared to placebo. Patients will randomly receive one of three Erenumab doses or a placebo without knowing which one.

Participant Groups

Group I: Dose level 2 Experimental Treatment 2 Interventions

Participants will be randomized to one of two doses determined by their body weight at Day 1. Participants who enrolled under the original protocol or protocol amendment 1 will be identified as group 1. Those enrolled under protocol amendment 2 will be identified as group 2.

Group II: Dose level 1 Experimental Treatment 2 Interventions

Participants will be randomized to one of two doses determined by their body weight at Day 1. Participants who enrolled under the original protocol or protocol amendment 1 will be identified as group 1. Those enrolled under protocol amendment 2 will be identified as group 2.

Group III: Placebo Placebo Group 1 Intervention

Participants will be randomized to a 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?

Amgen

Lead 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

Novartis

Industry Sponsor

Trials

1,646

Recruited

2,778,000+

Vasant Narasimhan

Novartis

Chief Executive Officer since 2018

MD from Harvard Medical School, Bachelor's in Biological Sciences from University of Chicago, Master's in Public Policy from John F. Kennedy School of Government

Shreeram Aradhye

Novartis

Chief Medical Officer since 2022

MD from Yale University, MSc in Clinical Epidemiology from University of Pennsylvania

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]

Erenumab, particularly at a dose of 140 mg, significantly reduces the number of monthly migraine days and increases the response rate in patients with episodic migraine, especially those with prior treatment failures.

The safety profile of erenumab is favorable, as no significant differences in adverse events were observed between the 140 mg and 70 mg doses, indicating that higher efficacy does not come with increased risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal Dose of Erenumab for Preventive Treatment of Episodic Migraine: A Systematic Review and Meta-Analysis. Yang, Y., Chen, M., Wu, D., et al.[2022]

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]

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]

In a real-world study involving 542 migraine patients treated with erenumab for at least three months, significant reductions in monthly headache frequency, migraine days, and headache intensity were observed, with over 75% of patients experiencing improvements.

The study confirmed that erenumab is effective in improving quality of life for migraine patients, with 83% of patients responding positively to treatment and 80% expressing satisfaction, particularly among those who had previously failed other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world evidence data on the monoclonal antibody erenumab in migraine prevention: perspectives of treating physicians in Germany. Straube, A., Stude, P., Gaul, C., et al.[2022]

The REFORM study enrolled 751 adults with migraine, primarily chronic migraine, to investigate biomarkers that could predict the response to erenumab, a treatment for migraine prevention.

Participants had a high migraine burden, averaging 14.5 migraine days per month, and many had previously failed multiple preventive medications, highlighting the need for effective treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Registry for Migraine (REFORM) study: methodology, demographics, and baseline clinical characteristics. Karlsson, WK., Ashina, H., Cullum, CK., et al.[2023]

Brivaracetam (BRV) is shown to be safe and well-tolerated in children and adolescents with focal epilepsy, with a high retention rate of 97% at three months and a median treatment duration of 180 days.

The efficacy of BRV is promising, with a 50% responder rate of 47% at three months, and it can be effectively switched from levetiracetam (LEV) at a 10:1 ratio, making it a viable option for patients experiencing adverse effects from LEV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postmarketing experience with brivaracetam in the treatment of focal epilepsy in children and adolescents. Schubert-Bast, S., Willems, LM., Kurlemann, G., et al.[2019]

New antiepileptic drugs like vigabatrin, rufinamide, perampanel, and clobazam have been FDA-approved and show promise in treating severe childhood epilepsy syndromes, which include infantile spasms and Dravet syndrome.

Recent genetic research is uncovering potential targeted therapies for pediatric epilepsy, suggesting that precision medicine could play a significant role in future treatments by addressing the underlying causes of these disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging Antiepileptic Drugs for Severe Pediatric Epilepsies. Mudigoudar, B., Weatherspoon, S., Wheless, JW.[2018]

In a long-term study involving 257 pediatric patients with epilepsy, adjunctive brivaracetam (BRV) treatment demonstrated significant efficacy, with patients aged 2 years and older experiencing a median 62.9% reduction in focal seizure frequency and over 50% achieving a ≥50% response in all seizures.

The treatment was generally well tolerated, with a high retention rate over six years (44.8% remaining on treatment), and cognitive and behavioral assessments showed stability or slight improvement, indicating that BRV is a safe option for managing epilepsy in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of adjunctive brivaracetam in pediatric patients with epilepsy: An open-label, follow-up trial. Lagae, L., Klotz, KA., Fogarasi, A., et al.[2023]

In a study of 124 pediatric patients with genetic epilepsy treated with perampanel (PER), the overall response rates were 51.6% at 6 months and 49.6% at 12 months, indicating that PER is an effective treatment option for this population.

Developmental delay was identified as a negative predictor of treatment response, while patients with pathogenic variants in the SCN1A gene showed significantly better responses to PER, highlighting the importance of genetic factors in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of perampanel in pediatric epilepsy with known and presumed genetic etiology. Miao, P., Zhu, X., Jin, W., et al.[2023]

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. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Optimal Dose of Erenumab for Preventive Treatment of Episodic Migraine: A Systematic Review and Meta-Analysis. [2022]

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

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

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

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

7. England pubmed.ncbi.nlm.nih.gov

Real-world evidence data on the monoclonal antibody erenumab in migraine prevention: perspectives of treating physicians in Germany. [2022]

8. England pubmed.ncbi.nlm.nih.gov

The Registry for Migraine (REFORM) study: methodology, demographics, and baseline clinical characteristics. [2023]

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

Postmarketing experience with brivaracetam in the treatment of focal epilepsy in children and adolescents. [2019]

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

Emerging Antiepileptic Drugs for Severe Pediatric Epilepsies. [2018]

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

Long-term safety and efficacy of adjunctive brivaracetam in pediatric patients with epilepsy: An open-label, follow-up trial. [2023]

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

Efficacy of perampanel in pediatric epilepsy with known and presumed genetic etiology. [2023]