Fremanezumab for Migraine

Overseen By Tolu ajayi

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Beth Israel Deaconess Medical Center

Must not be taking: Opioids, Marijuana, Sleep drugs, others

Disqualifiers: Severe cardiac disease, Cerebrovascular disease, Uncontrolled hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 6

Duration: 3 months

100 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you do not start or change the type, dosage, or frequency of any preventive medications for conditions other than migraine that might affect the study, such as antidepressants or beta-blockers. If you are currently on a migraine preventative therapy, you cannot participate in the trial.

What data supports the effectiveness of the drug fremanezumab for treating migraines?

Research shows that fremanezumab is effective in reducing the frequency of migraines in patients who have not had success with other preventive treatments, providing long-term relief over 24 weeks. ^{1 2 3 4 5}

Is fremanezumab safe for humans?

Fremanezumab has been shown to be generally safe in humans, with no serious treatment-related adverse events reported in clinical trials. The most common side effect is a mild-to-moderate reaction at the injection site, such as redness, pain, or swelling. ^{6 7 8 9 10}

How is the drug fremanezumab different from other migraine treatments?

Fremanezumab is unique because it is a fully humanized monoclonal antibody that specifically targets the calcitonin gene-related peptide (CGRP), which plays a key role in migraines. It is administered as a subcutaneous injection with flexible dosing options, either monthly or quarterly, making it convenient for patients. ^{6 9 11 12 13}

What is the purpose of this trial?

The main goal of this study is to determine whether there is a relationship between fremanezumab's ability to prevent migraine and improved sleep quality in migraine patients (fremanezumab is a FDA-approved humanized CGRP monoclonal antibody for the treatment of migraine). This is a within-person study design that examines treatment effects (changes) using high-resolution assessments. To complete the study, each participant will be observed using daily assessments of migraine and sleep outcomes before treatment (baseline: 0 to 30 days), and at 1, 2, and 3 months after treatment (injection 1: days 31-60, injection 2: days 61-90, injection 3: days 91-120). In essence, this creates an interrupted time-series design where repeated interventions are introduced at fixed intervals.

Research Team

Sait Ashina, MD

Principal Investigator

Beth Israel Deaconess Medical Center

Eligibility Criteria

Adults aged 18-65 with migraines, experiencing 10-25 headache days a month, at least 8 being migraine days lasting over 4 hours if untreated. Must score ≥10 on the Insomnia Severity Index but not have severe sleep disorders like obstructive sleep apnea or restless legs syndrome. Cannot be using certain pain or sleep medications regularly, have serious heart/cerebrovascular conditions, history of substance abuse within last 5 years, or be pregnant/nursing without birth control.

Inclusion Criteria

I have been diagnosed with migraine, following official guidelines.

I agree not to change my preventive medications unless it's for migraines.

Able to provide written informed consent

Exclusion Criteria

You have a history of feeling very scared in small, enclosed spaces.

I am currently taking prescription pain medication for headaches or body pain.

I have had a stroke, TIA, or surgery on the arteries in my neck.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

0-30 days

1 visit (in-person)

Baseline

Participants complete daily assessments of migraine and sleep outcomes before treatment

0-30 days

Daily assessments

Treatment

Participants receive fremanezumab injections and are monitored for migraine and sleep outcomes

3 months

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 month

1 visit (in-person)

Treatment Details

Interventions

• Fremanezumab

Trial Overview The trial is testing Fremanezumab's effect on preventing migraines and improving sleep quality in patients with frequent migraines. Participants will self-report daily assessments of migraine and sleep before treatment and for three months after starting treatment to see if there are changes in their condition.

Participant Groups

Group I: treatment effect Experimental Treatment 1 Intervention

No 2 arms and only 1 intervention

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?

Beth Israel Deaconess Medical Center

Lead Sponsor

Trials

872

Recruited

12,930,000+

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

Findings from Research

Fremanezumab significantly reduced monthly migraine days and headache days in patients with high-frequency episodic migraine and chronic migraine over a 24-week period, demonstrating early and sustained efficacy.

The treatment was well-tolerated with a low incidence of adverse events (2.4%), and no patients discontinued treatment, indicating a favorable safety profile for individuals with multiple preventive treatment failures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early and sustained efficacy of fremanezumab over 24-weeks in migraine patients with multiple preventive treatment failures: the multicenter, prospective, real-life FRIEND2 study. Barbanti, P., Egeo, G., Aurilia, C., et al.[2023]

In a study of 140 patients with chronic and episodic migraines, all three monoclonal antibodies (galcanezumab, fremanezumab, and erenumab) significantly reduced the number of monthly headache days and Migraine Disability Assessment (MIDAS) scores, indicating their effectiveness in treating migraines.

There were no significant differences in effectiveness among the three treatments, although galcanezumab and erenumab showed a faster reduction in headache days for patients with medication overuse headaches after 3 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A head-to-head observational cohort study on the efficacy and safety of monoclonal antibodies against calcitonin gene-related peptide for chronic and episodic migraine. Saccà, F., Braca, S., Sansone, M., et al.[2023]

The combination therapy of bevacizumab, irinotecan, and temozolomide showed high objective response rates of 66.6% for medulloblastoma and 75.0% for atypical teratoid/rhabdoid tumors in a study of 13 pediatric patients with relapsed CNS embryonal tumors.

The treatment resulted in favorable survival outcomes, with 12-month progression-free survival rates of 69.2% and overall survival rates of 67.1%, while adverse effects were manageable and mostly mild.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of bevacizumab, irinotecan, and temozolomide combination for relapsed or refractory pediatric central nervous system embryonal tumor: a single-institution study. Shiba, Y., Motomura, K., Taniguchi, R., et al.[2023]

A 33-year-old patient with neurofibromatosis type 2 (NF2) showed significant stabilization or reduction of multiple schwannomas and improvement in neurological symptoms after 2 years of treatment with the anti-VEGF antibody bevacizumab, despite the tumors having a high growth rate prior to treatment.

This case is the first to report a sustained response to bevacizumab in a patient with the NF2:c.784C>T p.(Arg262*) variant, suggesting that this genotype may influence treatment outcomes and could help guide therapy for other mosaic NF2 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sustained response to bevacizumab in a patient with mosaic neurofibromatosis type 2 carrying the NF2:c.784C>T p.(Arg262*) variant. Basenach, E., Förster, A., Raab, P., et al.[2022]

Temozolomide (TMZ) and bevacizumab (BEV) are effective chemotherapeutic agents for treating high-grade gliomas, but their mechanisms of action can vary, with TMZ potentially inducing cell death through apoptosis or autophagy, while BEV may cause cell death via hypoxia-induced autophagy.

Clinical trials indicate that newly diagnosed glioma patients have a longer overall survival (12-15 months) compared to those with recurrence (8-9 months), suggesting that combining TMZ with radiotherapy and BEV may enhance treatment efficacy, although further clinical trials are needed to determine the best treatment regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current evidence of temozolomide and bevacizumab in treatment of gliomas. Nanegrungsunk, D., Onchan, W., Chattipakorn, N., et al.[2022]

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]

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, a CGRP monoclonal antibody, has been shown to be effective in preventing both episodic and chronic migraines, with multiple clinical trials demonstrating its superiority over placebo.

The medication is well-tolerated, with treatment-related adverse reactions similar to those of placebo, primarily consisting of mild-to-moderate injection site reactions, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of Tolerability of Fremanezumab for Episodic and Chronic Migraine. Root, S., Ahn, K., Kirsch, J., et al.[2023]

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 calcitonin gene-related peptide, has been shown to be a generally safe and well-tolerated preventive treatment for chronic and episodic migraines in a pooled analysis of 2566 patients from four placebo-controlled studies.

The most common adverse events were mild to moderate injection site reactions, with serious adverse events being rare and not linked to the drug, indicating that fremanezumab has a favorable safety profile compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Tolerability of Fremanezumab for the Prevention of Migraine: A Pooled Analysis of Phases 2b and 3 Clinical Trials. Silberstein, SD., McAllister, P., Ning, X., et al.[2020]

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]

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]

References

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

Early and sustained efficacy of fremanezumab over 24-weeks in migraine patients with multiple preventive treatment failures: the multicenter, prospective, real-life FRIEND2 study. [2023]

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

A head-to-head observational cohort study on the efficacy and safety of monoclonal antibodies against calcitonin gene-related peptide for chronic and episodic migraine. [2023]

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

Efficacy and safety of bevacizumab, irinotecan, and temozolomide combination for relapsed or refractory pediatric central nervous system embryonal tumor: a single-institution study. [2023]

4. Germany pubmed.ncbi.nlm.nih.gov

Sustained response to bevacizumab in a patient with mosaic neurofibromatosis type 2 carrying the NF2:c.784C>T p.(Arg262*) variant. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Current evidence of temozolomide and bevacizumab in treatment of gliomas. [2022]

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

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

7. United States 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. [2022]

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

Review of Tolerability of Fremanezumab for Episodic and Chronic Migraine. [2023]

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

Fremanezumab: First Global Approval. [2019]

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

Safety and Tolerability of Fremanezumab for the Prevention of Migraine: A Pooled Analysis of Phases 2b and 3 Clinical Trials. [2020]

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

Fremanezumab as Add-On Treatment for Patients Treated With Other Migraine Preventive Medicines. [2022]

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

Delayed Injection Site Reaction to Fremanezumab for Chronic Migraine Treatment. [2023]

13. England pubmed.ncbi.nlm.nih.gov

Fremanezumab blocks CGRP induced dilatation in human cerebral, middle meningeal and abdominal arteries. [2019]