Emgality for Migraine Prevention

Overseen By Rami Burstein

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Beth Israel Deaconess Medical Center

Must not be taking: Antidepressants, Anticonvulsants, Beta-blockers

Disqualifiers: Cardiac disease, Cerebrovascular disease, Substance abuse, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

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

Compensation: Varies

Number of Visits: 9

Duration: 3 months

64 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

You may need to stop taking your current migraine preventative medications, as the trial excludes those on such therapies. However, you can continue other medications as long as you don't change their type, dosage, or frequency during the study.

What data supports the effectiveness of the drug Emgality for migraine prevention?

Research shows that Galcanezumab (Emgality) is effective in preventing migraines, as it improved quality-of-life and reduced disability in patients with both episodic and chronic migraines during Phase 3 trials. It is approved by the US FDA and the EMA for preventing migraines in adults who experience at least 4 migraine days per month. ^{1 2 3 4 5}

Is Emgality (Galcanezumab) safe for humans?

Emgality (Galcanezumab) has been found to be safe for the preventive treatment of migraines in adults, based on clinical trials and long-term studies. ^{1 2 3 6 7}

How is the drug Emgality unique for migraine prevention?

Emgality is unique because it is a monoclonal antibody that targets the calcitonin gene-related peptide (CGRP), which plays a key role in causing migraines. It is administered as a once-monthly injection, offering a convenient option for those who need preventive treatment. ^{1 8 9 10 11}

What is the purpose of this trial?

The purpose of this study is to understand better the mechanisms of action of calcitonin gene related peptide (CGRP) targeted monoclonal antibodies in migraine prevention. Specifically, the protocol will allow the investigators to determine whether the main site of action of this novel and recently-approved class of migraine prophylactic drugs act inside or outside the brain and if so, where.

Research Team

Rami Burstein

Principal Investigator

Beth Israel Deaconess Medical Center

Eligibility Criteria

This trial is for adults aged 18-65 with a history of migraines, experiencing 10-25 headache days per month. Participants must not be on migraine prevention therapy or have other significant pain issues, severe cardiac disease, substance abuse history, or use marijuana. Pregnant women and those not using birth control are excluded.

Inclusion Criteria

I have 10-25 headache days a month, with at least 8 being long-lasting migraines.

I have been diagnosed with migraine, following official guidelines.

My migraines started when I was 50 or younger.

Exclusion Criteria

My blood pressure is not higher than 160/100 mm Hg.

I have had botulinum toxin or anti-CGRP-mAb injections in the past 6 months.

I have used marijuana or CBD oil in the past year.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

2 visits (in-person)

Pre-Treatment Assessment

Participants undergo medical and headache history review, physical examination, and e-diary education

1 month

3 visits (in-person)

Treatment

Participants receive galcanezumab treatment and undergo fMRI sessions

3 months

3 visits (in-person)

Follow-up

Participants are monitored for changes in migraine triggers and brain functioning

1 month

1 visit (in-person)

Treatment Details

Interventions

• Galcanezumab

Trial Overview The study tests the effects of Emgality (Galcanezumab), a CGRP-targeted monoclonal antibody for preventing migraines. It aims to determine whether its main effect is inside or outside the brain and identify specific action sites.

Participant Groups

Group I: Treatment Experimental Treatment 1 Intervention

Effects of galacenezumab (emgality) treatment (injectable 240 mg initial dose followed by 120 mg treatments 1 and 2 month later) on brain functioning.

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

Approved in European Union as Emgality for:

• Prophylaxis of migraine in adults who have at least four migraine days per month

Approved in United States as Emgality for:

• Preventive treatment of migraine in adults
• Treatment of episodic cluster headache

Who Is Running the Clinical Trial?

Beth Israel Deaconess Medical Center

Lead Sponsor

Trials

872

Recruited

12,930,000+

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Findings from Research

Galcanezumab is a humanized monoclonal antibody that targets the calcitonin gene-related peptide (CGRP), which plays a key role in migraine development, and was approved by the FDA in September 2018 for the preventive treatment of migraines in adults.

The approval was based on its efficacy in reducing the frequency of migraine days for adults experiencing at least 4 migraines per month, and it is also being studied for the prevention of cluster headaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Galcanezumab: First Global Approval. Lamb, YN.[2019]

Galcanezumab (GMB) treatment significantly reduced annual indirect costs for patients with episodic migraine (EM), leading to improved productivity at work, household tasks, and leisure activities, as shown in a study of 805 EM patients.

While GMB also provided cost savings for chronic migraine (CM) patients, these were not statistically significant, indicating that the most pronounced benefits of GMB are seen in those with episodic migraine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Annual indirect costs savings in patients with episodic or chronic migraine: a post-hoc analysis of phase 3 galcanezumab clinical trials in the United States. Varnado, OJ., Ye, W., Mi, X., et al.[2023]

In a post hoc analysis of patients with episodic (N=879) and chronic (N=555) migraine who did not show significant improvement after 1 month of galcanezumab treatment, a notable percentage still achieved 'good' responses with continued treatment, especially those with 'modest' early improvement (62% for episodic and 38% for chronic).

Even patients with minimal or no early improvement had some chance of achieving a 'good' response with ongoing treatment, although the likelihood was lower, indicating that continued treatment may still be beneficial for certain patients despite initial lack of response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of Initial Nonresponders to Galcanezumab in Patients With Episodic or Chronic Migraine: Results From the EVOLVE-1, EVOLVE-2, and REGAIN Randomized, Double-Blind, Placebo-Controlled Studies. Nichols, R., Doty, E., Sacco, S., et al.[2020]

In a study involving 1113 patients with chronic migraine, treatment with galcanezumab significantly improved quality of life and reduced disability compared to placebo, with notable improvements in functioning as measured by the Migraine-Specific Quality-of-Life Questionnaire.

At the 3-month mark, patients receiving galcanezumab (both 120 mg and 240 mg doses) showed greater reductions in migraine-related disability compared to placebo, indicating that galcanezumab is an effective treatment option for enhancing patient functioning in chronic migraine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in patient functioning and disability: results from a phase 3, double-blind, randomized, placebo-controlled clinical trial evaluating galcanezumab for chronic migraine prevention (REGAIN). Ford, J., Tassorelli, C., Leroux, E., et al.[2021]

In a real-world study of 52 patients in Japan, galcanezumab significantly reduced monthly migraine days by an average of 5.9 days after three doses, demonstrating its efficacy in treating migraines.

The treatment also improved associated symptoms like photophobia and nausea in over half of the patients, although more than 60% reported premonitory symptoms without subsequent headaches, indicating a need for further monitoring of these effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world evidence of galcanezumab for migraine treatment in Japan: a retrospective analysis. Takizawa, T., Ohtani, S., Watanabe, N., et al.[2023]

Galcanezumab, a monoclonal antibody, demonstrated significant efficacy in reducing monthly migraine headache days over a 12-month period, with patients experiencing an average reduction of 8.0 to 9.0 days from a baseline of 19.4 days.

The treatment was found to be safe and well-tolerated, with a low discontinuation rate of 5% due to adverse events, indicating high adherence among patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term treatment with galcanezumab in patients with chronic migraine: results from the open-label extension of the REGAIN study. Pozo-Rosich, P., Detke, HC., Wang, S., et al.[2022]

Galcanezumab, a monoclonal antibody targeting the CGRP ligand, has shown significant efficacy in reducing the frequency of migraine attacks in both episodic and chronic migraine patients, as demonstrated in phase 3 studies involving multiple months of treatment.

Patients receiving galcanezumab reported improved quality of life and functioning, with a high percentage achieving substantial reductions in migraine days, and the treatment was well tolerated over a 12-month period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Galcanezumab for the Preventive Treatment of Migraine: A Narrative Review. Martin, V., Samaan, KH., Aurora, S., et al.[2021]

References

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

Galcanezumab: First Global Approval. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Annual indirect costs savings in patients with episodic or chronic migraine: a post-hoc analysis of phase 3 galcanezumab clinical trials in the United States. [2023]

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

Analysis of Initial Nonresponders to Galcanezumab in Patients With Episodic or Chronic Migraine: Results From the EVOLVE-1, EVOLVE-2, and REGAIN Randomized, Double-Blind, Placebo-Controlled Studies. [2020]

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

Effect of Different Doses of Galcanezumab vs Placebo for Episodic Migraine Prevention: A Randomized Clinical Trial. [2022]

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

Changes in patient functioning and disability: results from a phase 3, double-blind, randomized, placebo-controlled clinical trial evaluating galcanezumab for chronic migraine prevention (REGAIN). [2021]

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

Real-world evidence of galcanezumab for migraine treatment in Japan: a retrospective analysis. [2023]

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

Long-term treatment with galcanezumab in patients with chronic migraine: results from the open-label extension of the REGAIN study. [2022]

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

Galcanezumab: A Review in the Prevention of Migraine and Treatment of Episodic Cluster Headache. [2021]

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

Efficacy and Safety of Galcanezumab for the Preventive Treatment of Migraine: A Narrative Review. [2021]

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

Once-monthly galcanezumab for the prevention of migraine in adults: an evidence-based descriptive review and potential place in therapy. [2020]

11. England pubmed.ncbi.nlm.nih.gov

Efficacy of galcanezumab in patients with migraine who did not benefit from commonly prescribed preventive treatments. [2021]