Fremanezumab for Menstrual Migraine

Overseen By Emily Lyford

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: Brigham and Women's Hospital

Must not be taking: Opioids, Barbiturates, CGRP therapies, others

Disqualifiers: Pregnancy, Cardiovascular disease, Cancer, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 6 months

72 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if fremanezumab, an injectable medicine, can reduce migraines associated with menstrual periods. Participants will receive either the active medicine or a placebo (inactive substitute) and will record their migraine experiences in diaries. The trial targets women aged 18 to 45 who have migraines linked to their menstrual cycle and have experienced these migraines for at least six months. As a Phase 4 trial, this research seeks to understand how the already FDA-approved and effective treatment benefits a broader range of patients.

Will I have to stop taking my current medications?

The trial requires that you do not start any new migraine preventive medications during the study. However, it does not specify if you need to stop taking your current medications, so it's best to discuss this with the study team.

What is the safety track record for fremanezumab?

Studies have shown that fremanezumab is generally well-tolerated by patients. Research involving over 2,800 people with occasional or frequent migraines found fremanezumab to be safe, as it did not cause major heart or brain problems. Reports confirmed its safety over a 12-week period compared to a placebo, a substance with no active medicine. While no treatment is entirely risk-free, fremanezumab's history suggests it is safe for most people. Prospective trial participants can find reassurance in this information regarding the treatment's safety. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Fremanezumab is unique because it targets the calcitonin gene-related peptide (CGRP) pathway, which is a key player in the development of migraines. Unlike standard treatments for menstrual migraines, such as NSAIDs and hormonal therapies, fremanezumab directly interrupts the migraine process by blocking CGRP, a protein that spikes during migraines and contributes to pain and inflammation. Researchers are excited about fremanezumab because it offers a targeted approach that could potentially provide relief for those who haven't responded well to existing treatments. Plus, its dosing schedule—just once every three months—could make it a convenient option for patients seeking long-lasting migraine control.

What is the effectiveness track record for fremanezumab in treating menstrual migraines?

Research has shown that fremanezumab, which participants in this trial may receive, effectively reduces the number of migraine days. This treatment targets a specific pathway in the body. Studies found that over 66% of people with occasional migraines and about 51.6% with frequent migraines experienced a significant reduction—at least 50%—in their monthly migraine days. In simpler terms, more than half of the patients had fewer migraines after using fremanezumab. This is promising for those who suffer from migraines, especially those linked to menstruation. The evidence suggests that this treatment can provide meaningful relief for many people. ^{3 6 7 8 9}

Who Is on the Research Team?

Carolyn A Bernstein, MD

Principal Investigator

Brigham and Women's

Are You a Good Fit for This Trial?

This trial is for women aged 18-45 who suffer from migraines during their menstrual period. Participants should have a diagnosis of migraine, which can also occur at other times of the month. They must be willing to receive injections, keep a diary on their headaches, and provide saliva samples.

Inclusion Criteria

I weigh at least 45 kg and my BMI is between 17.5 and 34.9.

I can sign and follow the study's rules.

I have been diagnosed with migraines related to my menstrual cycle.

Exclusion Criteria

The patient is overusing acute medication

The patient has participated in a clinical study of a new chemical entity or a prescription medicine within a specified timeframe

I am currently on or have been treated with specific therapies.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive fremanezumab or placebo injections every three months for two treatments, with monitoring through diaries and hormone level tests

6 months

3 visits (in-person), 5 visits (virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of migraine days, severity, and quality of life

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Fremanezumab

Trial Overview

The study tests if fremanezumab, an injectable medication targeting the CGRP pathway, can reduce menstruation-related migraines. It involves comparing this drug with a placebo over two treatment sessions every three months.

How Is the Trial Designed?

Group I: Patients receiving active medication Active Control 1 Intervention

These patients will receive 675 mg of fremanezumab for two total doses administered 3 months apart.

Group II: Patients receiving placebo Placebo Group 1 Intervention

These patients will receive placebo injections for two total doses administered 3 months apart.

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

Approved in United States as Ajovy for:

• Prevention of migraines in adults

Approved in European Union as Ajovy for:

• Prevention of migraines in adults

Approved in United Kingdom as Ajovy for:

• Prevention of migraines in adults

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Teva Pharmaceuticals USA

Industry Sponsor

Trials

232

Recruited

189,000+

Dr. Eric A. Hughes

Teva Pharmaceuticals USA

Chief Medical Officer since 2022

MD and PhD from Yale School of Medicine

Richard Francis

Teva Pharmaceuticals USA

Chief Executive Officer since 2023

BSc in Biochemistry from Imperial College London

Published Research Related to This Trial

Ajovy (fremanezumab) is an effective monoclonal antibody for preventing migraines, showing positive results in Phase III clinical trials for both episodic and chronic migraine sufferers.

The treatment has a favorable safety profile, with no serious adverse events reported, making it a promising option for adults experiencing frequent migraines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fremanezumab autoinjector pen for the prevention of migraine. Weatherall, MW.[2022]

In a study involving 462 women with menstrually related migraine (MRM), galcanezumab significantly reduced the number of monthly migraine headache days compared to placebo, with a mean reduction of 5.1 days versus 3.2 days (p < 0.001).

Galcanezumab also showed effectiveness in reducing perimenstrual migraine days and improving overall quality of life, indicating its potential as a valuable treatment option for women suffering from MRM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of galcanezumab in women with episodic migraine meeting criteria for menstrually related migraine: A post hoc analysis of EVOLVE-1 and EVOLVE-2. MacGregor, EA., Okonkwo, R., Detke, HC., et al.[2023]

Fremanezumab, a monoclonal antibody targeting calcitonin gene-related peptide, significantly reduced the number of moderate to severe headache days in patients with chronic migraine (CM) and episodic migraine (EM) by 34.5% to 43.4% compared to placebo over 12 weeks, based on data from 2843 participants across three studies.

Both quarterly and monthly dosing of fremanezumab also led to significant reductions in the total hours of moderate to severe headaches, demonstrating its efficacy even in patients who had previously not responded well to other migraine treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduction in the severity and duration of headache following fremanezumab treatment in patients with episodic and chronic migraine. Ashina, M., Cohen, JM., Gandhi, SK., et al.[2021]

Fremanezumab significantly reduced the average number of moderate to severe headache days in Japanese and Korean patients with chronic migraine, showing a reduction of 4.1 days per month compared to 2.4 days for placebo over 12 weeks.

The treatment was well tolerated, with a similar rate of adverse events, including injection-site reactions, compared to placebo, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of fremanezumab for chronic migraine prevention: Multicenter, randomized, double-blind, placebo-controlled, parallel-group trial in Japanese and Korean patients. Sakai, F., Suzuki, N., Kim, BK., et al.[2022]

Fremanezumab, an anti-CGRP monoclonal antibody, effectively antagonizes the relaxing effects of CGRP on human arteries, indicating its potential role in migraine prevention by affecting vascular responses.

The study demonstrated that CGRP causes significant relaxation in human arteries, with fremanezumab showing a dose-dependent reduction in this effect, suggesting that it may modulate vascular responses across different types of arteries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fremanezumab blocks CGRP induced dilatation in human cerebral, middle meningeal and abdominal arteries. Ohlsson, L., Kronvall, E., Stratton, J., et al.[2019]

Fremanezumab is a fully humanized monoclonal antibody that targets calcitonin gene-related peptide, which plays a key role in migraine pathophysiology, and has shown significant reductions in migraine frequency and related disability in phase III studies involving adults.

Approved by the US FDA in September 2018 for preventive migraine treatment, fremanezumab is also being explored for cluster headaches and post-traumatic headache disorder, although a study for chronic cluster headaches was suspended due to futility analysis results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fremanezumab: First Global Approval. Hoy, SM.[2019]

Fremanezumab, a monoclonal antibody targeting CGRP, significantly reduced the number of migraine days in patients with episodic and chronic migraines who were already on stable preventive medications, showing a reduction of 12.4 days compared to 7.4 days for placebo.

The treatment was found to be safe, with mostly mild and transient side effects, and no serious adverse events linked to the treatment, indicating it can be a reliable add-on therapy for migraine prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fremanezumab as Add-On Treatment for Patients Treated With Other Migraine Preventive Medicines. Cohen, JM., Dodick, DW., Yang, R., et al.[2022]

Fremanezumab, a monoclonal antibody for migraine treatment, can cause delayed injection site reactions, as demonstrated in a case involving a 25-year-old female who experienced symptoms 8 days after her second injection.

The patient successfully managed her symptoms of redness, itching, and pain with a 1-month course of prednisone, indicating that systemic therapy may be necessary for delayed reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delayed Injection Site Reaction to Fremanezumab for Chronic Migraine Treatment. Thomas, KV., Bennett, DD., Endo, J.[2023]

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tevausa.com/news-and-media/press-releases/final-data-from-tevas-pearl-real-world-study-reinforce-the-long-term-effectiveness-of-ajovy-fremanezum/

Final Data from Teva's PEARL Real-World Study Reinforce ...

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AJOVY® (fremanezumab) significantly reduced monthly migraine days (MMD) and monthly headache days (MHD) versus placebo over a 12-week period ...

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Statistical Review and Evaluaton Ajovy (fremanezumab-vfrm)

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