IPN10200 for Migraine Prevention

(MERANTI Trial)

Recruiting at 15 trial locations

Overseen By Ipsen Clinical Study Enquiries

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Ipsen

Must not be taking: Opioids, Barbiturates, Cannabinoids, others

Disqualifiers: Uncontrolled psychiatric, Neuromuscular, Respiratory, 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

641 Participants Needed

Trial Summary

What is the purpose of this trial?

A migraine is a headache with severe throbbing pain or a pulsating sensation, usually on one side of the head. It is often accompanied by feeling or being sick and a sensitivity to bright lights and sound. Migraines are caused by a series of events when the brain gets stimulated or activated, which causes the release of chemicals that cause pain. IPN10200 is a medication that stops the release of these chemical messengers. Participants with episodic migraine (EM) or chronic migraine (CM) will be included in both Step 1 and Step 2. "Headache days" are when participants experience headaches that meet the criteria for a migraine or a headache without the additional migraine-specific symptoms. "Migraine days" occur when the headache displays clear migraine characteristics. This study aims to determine: * The safety and efficacy of injecting IPN10200 directly into the muscles of the head and neck to prevent EM and CM, * The right amount (dose) of IPN10200 to inject at each point, * The total amount (dose) of IPN10200 that provides the best balance between safety and efficacy preventing migraines. Participants will need to complete a daily electronic migraine Diary (eDiary) and questionnaires throughout the study. The total study duration for a participant will be up to 44 weeks.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does list certain medications that cannot be used before joining the study, like botulinum toxin, CGRP blockers, and some others. It's best to discuss your current medications with the study team to see if they might interfere with the trial.

What data supports the effectiveness of the drug IPN10200, which involves Botulinum toxin, for migraine prevention?

Research shows that Botulinum toxin type A has been used successfully for over a decade to prevent chronic migraines, reducing the frequency, severity, and duration of headaches. It is well-tolerated and remains an important option for patients who do not respond well to other preventive treatments. ^{1 2 3 4 5}

Is IPN10200 (Botulinum toxin) safe for humans?

Research shows that Onabotulinumtoxin A, a form of Botulinum toxin, is generally safe for treating chronic migraines, with fewer side effects than some oral medications like topiramate. However, it can cause more treatment-related side effects than a placebo, so further studies are needed to fully understand its safety. ^{2 5 6 7 8}

How does the drug IPN10200 (Botulinum toxin) differ from other migraine treatments?

IPN10200, or Botulinum toxin, is unique because it works by targeting nerve signals to prevent chronic migraines, unlike newer treatments that focus on blocking specific proteins involved in migraine pathways. It is administered through injections, which is different from oral medications, and is particularly useful for patients who cannot tolerate or do not respond to other preventive medications. ^{2 4 5 9 10}

Research Team

Ipsen Medical Director

Principal Investigator

Ipsen

Eligibility Criteria

Adults aged 18-80 with a history of episodic or chronic migraines, diagnosed before age 50 and lasting at least 12 months. Participants must have tried one migraine prevention treatment, be able to consent, and record their headache frequency in an eDiary. Those with chronic migraines should have ≥15 headache days per month; for episodic migraines ≤14 headache days but ≥6 migraine days are required.

Inclusion Criteria

Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF. Participant has provided written informed consent and signed privacy/data protection documentation

I am between 18 and 80 years old.

I have tried at least one preventive treatment for my migraines.

Exclusion Criteria

Actively suicidal patients

I am not pregnant, nursing, or if capable of becoming pregnant, I agree to use contraception.

I am taking more than one approved preventive migraine treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment - Step 1

Participants receive IPN10200 or placebo injections in muscles of the head, face, and neck. Safety is monitored throughout the 36 weeks.

36 weeks

Treatment - Step 2

New eligible participants are divided into groups based on diagnosis and receive Dose A, Dose B, or placebo. Monitored for efficacy and safety until Week 36.

36 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• IPN10200

Trial Overview The trial is testing IPN10200's ability to prevent severe headaches in adults by injecting it into the muscles of the head and neck. It will determine the safest and most effective dose for reducing migraine frequency as recorded in participants' daily electronic diaries over up to 44 weeks.

Participant Groups

Group I: Step 2- EM group IPN10200 Dose B Experimental Treatment 1 Intervention

Dose B will be administered to the participants in a single treatment cycle

Group II: Step 2- EM group IPN10200 Dose A Experimental Treatment 1 Intervention

Dose A will be administered to the participants in a single treatment cycle.

Group III: Step 2- CM group IPN10200 Dose B Experimental Treatment 1 Intervention

Dose B will be administered to the participants in a single treatment cycle

Group IV: Step 2- CM group IPN10200 Dose A Experimental Treatment 1 Intervention

Dose A will be administered to the participants in a single treatment cycle

Group V: Step 1 - Cohort 2 - IPN10200 Experimental Treatment 1 Intervention

Participants will receive IPN10200 dose B through injections at Day 1.

Group VI: Step 1 - Cohort 1- IPN10200 Experimental Treatment 1 Intervention

Participants will receive IPN10200 dose A through injections at Day 1.

Group VII: Step 1 - Cohort 1 - Placebo Placebo Group 1 Intervention

Participants will receive placebo through injections at Day 1.

Group VIII: Step 1 - Cohort 2 - Placebo Placebo Group 1 Intervention

Participants will receive placebo through injections at Day 1.

Group IX: Step 2- CM group placebo Placebo Group 1 Intervention

Placebo will be administered to the participants in a single treatment cycle

Group X: Step 2- EM group placebo Placebo Group 1 Intervention

Placebo will be administered to the participants in a single treatment cycle

IPN10200 is already approved in United States, European Union for the following indications:

Approved in United States as Botox for:

• Chronic migraine
• Other indications not related to IPN10200 specifically

Approved in European Union as Botox for:

• Chronic migraine
• Other indications not related to IPN10200 specifically

Who Is Running the Clinical Trial?

Ipsen

Lead Sponsor

Trials

358

Recruited

74,600+

David Loew

Ipsen

Chief Executive Officer since 2020

BA in Business Administration and MBA from the University of St. Gallen, Switzerland

Sandra Silvestri

Ipsen

Chief Medical Officer since 2023

MD, PhD

Findings from Research

Botulinum toxin treatment significantly reduces the frequency of migraine days by an average of 2 days per month in adults with chronic migraines, based on a systematic review of 28 trials involving 4190 participants.

While botulinum toxin has a higher relative risk of treatment-related adverse events compared to placebo, it shows a lower risk compared to other active treatments, indicating a favorable safety profile for chronic migraine management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cochrane systematic review and meta-analysis of botulinum toxin for the prevention of migraine. Herd, CP., Tomlinson, CL., Rick, C., et al.[2020]

Botulinum toxins are effective preventive treatments for patients with moderate to severe migraines, particularly for those who do not respond to traditional medications or experience intolerable side effects.

Studies have shown significant reductions in migraine frequency, severity, and duration with botulinum toxin treatments, especially in patients with the most severe headaches, highlighting the need for further research to optimize treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Botulinum toxins in the treatment of migraine and tension-type headaches. Winner, P.[2019]

OnabotulinumtoxinA (BOTOX) significantly reduces the frequency of headache days in adults with chronic migraine, showing a mean decrease of 8.4 days compared to 6.6 days for placebo over 24 weeks, indicating its efficacy as a prophylactic treatment.

The treatment was generally safe and well tolerated, with most adverse events being mild to moderate, and only a small percentage of patients discontinuing due to side effects (3.8% for onabotulinumtoxinA vs. 1.2% for placebo).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

OnabotulinumtoxinA for treatment of chronic migraine: pooled results from the double-blind, randomized, placebo-controlled phases of the PREEMPT clinical program. Dodick, DW., Turkel, CC., DeGryse, RE., et al.[2018]

Botulinum toxin type A is a well-tolerated preventive treatment for chronic migraine, with over a decade of established use, and its unique mechanism of action differs from newer CGRP-targeting monoclonal antibodies, suggesting both treatments will coexist in migraine management.

Future research may lead to the development of new botulinum toxin types that specifically target sensory pain neurons, potentially enhancing its effectiveness in treating chronic migraine and other headache disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Botulinum Toxin in the Treatment of Headache. Becker, WJ.[2021]

In a study of 19 Japanese adults with frequent migraines, Botulinum Toxin Type A (BoNT-A) injections significantly reduced migraine-related disability, as measured by the MIDAS score, two months after treatment.

No serious side effects were reported, indicating that BoNT-A is a safe option for migraine prophylaxis, although further randomized controlled trials are needed to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Botulinum toxin type A for migraine prophylaxis in the Japanese population: an open-label prospective trial. Suzuki, K., Iizuka, T., Sakai, F.[2019]

Onabotulinumtoxin A is an effective treatment for chronic migraine, approved since 2010, and works by targeting the release of neurotransmitters and neuropeptides involved in headache mechanisms.

While onabotulinumtoxin A is associated with more treatment-related adverse events than a placebo, it has fewer side effects compared to the oral medication topiramate, indicating a relatively favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Onabotulinumtoxin A in Chronic Migraine: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. Corasaniti, MT., Bagetta, G., Nicotera, P., et al.[2023]

An open-label study was conducted to assess the safety and effectiveness of botulinum toxin type A injections in patients with chronic migraine who did not respond to at least three different prophylactic medications.

The study highlights the potential of botulinum toxin type A as a treatment option for chronic migraine sufferers, particularly those who have not found relief with standard preventive therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Botox therapy for refractory chronic migraine. Conway, S., Delplanche, C., Crowder, J., et al.[2010]

Botulinum toxin A significantly reduces the number of headaches per month in adults with chronic daily headaches and chronic migraines, with a reduction of about 2 headaches per month in both groups based on pooled analyses of 3 and 5 studies, respectively.

However, botulinum toxin A does not show a significant effect on episodic migraines or chronic tension-type headaches, and it is associated with some side effects like blepharoptosis and neck stiffness compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Botulinum toxin A for prophylactic treatment of migraine and tension headaches in adults: a meta-analysis. Jackson, JL., Kuriyama, A., Hayashino, Y.[2022]

In a 24-month study involving 641 adults with chronic migraine, treatment with onabotulinumtoxinA significantly reduced headache days from an average of 20.6 to 7.4 days, demonstrating its effectiveness as a preventive treatment.

The treatment was generally well-tolerated, with 18.3% of patients reporting mild to moderate adverse drug reactions, and no new safety concerns were identified, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open-label prospective study of the real-life use of onabotulinumtoxinA for the treatment of chronic migraine: the REPOSE study. Ahmed, F., Gaul, C., García-Moncó, JC., et al.[2020]

OnabotulinumtoxinA (BOTOX®) significantly reduces the number of headache days and the need for acute headache medication in chronic migraine patients, with improvements observed at approximately 24 and 52 weeks based on data from 44 studies involving real-world effectiveness.

The treatment also enhances quality of life, as indicated by improvements in the Migraine-Specific Quality-of-Life score, and shows a response rate of over 46% for at least a 50% reduction in migraine days, confirming its efficacy as a preventive treatment for chronic migraines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of onabotulinumtoxinA (BOTOX®) for the preventive treatment of chronic migraine: A meta-analysis on 10 years of real-world data. Lanteri-Minet, M., Ducros, A., Francois, C., et al.[2023]

References

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

Cochrane systematic review and meta-analysis of botulinum toxin for the prevention of migraine. [2020]

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

Botulinum toxins in the treatment of migraine and tension-type headaches. [2019]

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

OnabotulinumtoxinA for treatment of chronic migraine: pooled results from the double-blind, randomized, placebo-controlled phases of the PREEMPT clinical program. [2018]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Botulinum Toxin in the Treatment of Headache. [2021]

5. Japan pubmed.ncbi.nlm.nih.gov

Botulinum toxin type A for migraine prophylaxis in the Japanese population: an open-label prospective trial. [2019]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Safety of Onabotulinumtoxin A in Chronic Migraine: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. [2023]

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

Botox therapy for refractory chronic migraine. [2010]

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

Botulinum toxin A for prophylactic treatment of migraine and tension headaches in adults: a meta-analysis. [2022]

9. England pubmed.ncbi.nlm.nih.gov

An open-label prospective study of the real-life use of onabotulinumtoxinA for the treatment of chronic migraine: the REPOSE study. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Effectiveness of onabotulinumtoxinA (BOTOX®) for the preventive treatment of chronic migraine: A meta-analysis on 10 years of real-world data. [2023]