Clinical trial NCT06625060: A Study to Evaluate IPN10200 Safety and Efficacy in the Prevention of Episodic or Chronic Migraine in Adults
Official title: A Multicentre, Randomised, Double-blind, Placebo-controlled, Dose Escalation and Dose Finding Phase II Study to Evaluate the Safety and Efficacy of IPN10200 in the Prevention of Episodic or Chronic Migraine in Adults
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Episodic Migraine
Chronic Migraine
Lead sponsor: Ipsen
Sponsor class: INDUSTRY
First posted: 2024-10-03
Enrollment: 641
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Model Description
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: The study will consist of 3 periods:

1. A 'screening period' to assess whether the participant can take part in the study.
2. Step 1 is divided in two cohorts. The study will assess sequentially the safety of two doses of IPN10200, a lower dose in the cohort 1 and a higher dose in cohort 2. Participants will be administered with the study drug or placebo. The treatment is injected in muscles of the head, face and neck. The safety of participants is monitored throughout the 36 weeks at each cohort.
3. Step 2: In this step, new eligible participants will be divided into two groups based on their diagnosis (EM or CM). These groups will then be randomly assigned to one of three intervention groups: Dose A, Dose B, or a placebo. The intervention will be given in a series of injections in muscles of the head, face and neck. Participants will be monitored for both efficacy and safety until they complete the Week 36 visit (the end of study).

Eligibility criteria: Inclusion Criteria:

1. 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;
2. Male or female ≥18 to 80 years of age at the time of signing the informed consent;
3. Diagnosis of either EM or CM, per ICHD-3 criteria, for at least 12 months prior to the screening visit;
4. Diagnosis of migraine at ≤50 years of age;
5. Participants in the EM group: History of EM diagnosis and headache frequency (i.e. migraine and non-migraine headache): ≤14 headache days in the 4 weeks prior to randomisation on study Day 1 based on information recorded in the eDiary; migraine frequency: ≥6 migraine days in the 4 weeks prior to randomisation on study Day 1 based on information recorded in the eDiary;
6. Participants in the CM group: History of CM diagnosis and headache frequency (i.e. migraine and non-migraine headache): ≥15 headache days in the 4 weeks prior to randomisation on study Day 1 based on information recorded in the eDiary; migraine frequency: ≥8 migraine days in the 4 weeks prior to randomisation on study Day 1 based on information recorded in the eDiary;
7. Participant with a history of use of at least one preventive treatment for migraine.

Exclusion Criteria:

1. History or current diagnosis of migraine with brainstem aura, retinal migraine, complications of migraine, tension-type headache, trigeminal autonomic cephalalgias, hypnic headache, hemicrania continua or new daily persistent headache;
2. Headache attributed to another disorder (e.g. secondary headaches), except medication overuse headache (MOH);
3. Current uncontrolled psychiatric or psychological condition, or one that could confound assessment of headaches/migraines or interfere with study participation;
4. Risk of self-harm or harm to others as evidenced by past suicidal behaviour or endorsing items 3, 4, or 5 on the C-SSRS at screening or Day 1.
5. Participants presenting with a swallowing disorder of any origin which might be exacerbated by botulinum toxin treatment, such as:

   - Grade 3 or 4 on the Dysphagia Severity Scale (severe dysphagia) with swallowing difficulties and requiring a change in diet.
6. Clinically relevant skin condition or infection that could interfere with injection of study intervention;
7. Participant has any medical condition or situation that would make them unsuitable for participation in the study;
8. Participant receiving more than one allowable concomitant migraine preventive treatment;
9. Known history of an inadequate response to \>4 medications prescribed for the prevention of migraine (2 of which have different mechanisms of action to botulinum toxin);
10. Use of any of the following medications in the specified timeframe prior to the screening visit:

    * Botulinum toxin for migraine within 24 weeks (or for any other medical/aesthetic reason within 16 weeks);
    * Prior use of mAbs blocking CGRP pathway within 12 weeks for preventative treatment of migraine
    * Prior use of oral CGRP receptor antagonist (gepants) for preventative treatment of migraine within 2 weeks;
    * Anaesthetic or steroid injection in any region targeted for treatment with study medication within 4 weeks;
    * Use of cannabidiol or other types of cannabinoids within 30 days;
    * Use of medical device to treat migraine within 4 weeks (e.g. non-invasive neuromodulation therapies such as nerve stimulation (gammaCore), transcranial magnetic stimulation (cephaly), external trigeminal nerve stimulation, transcutaneous electrical nerve stimulation and peripheral neuroelectrical stimulation);
    * Use of other intervention to treat migraine that is assessed to interfere with study evaluations within 4 weeks (e.g. acupuncture in the head and neck region, cranial traction, nociceptive trigeminal inhibition, occipital nerve block treatments and dental splints for headache);
    * Use of opioids or barbiturates for more than 2 days/month within the last 4 weeks.
11. Concurrent participation in another interventional clinical study (or within specified timeframe according to national or local legislation or requirements);
12. Diagnosis of other significant pain disorders that could confound the assessment of headaches/migraines or interfere with study participation, including but not limited to chronic pain disorders such as fibromyalgia, chronic low back pain and complex regional pain syndrome;
13. Pregnant women, nursing women, premenopausal women, or WOCBP (i.e. not surgically sterile or 1 year postmenopausal) not willing to practice an acceptable contraceptive method, at the beginning of the study and for a minimum of 12 weeks following the administration of study treatment;
14. Male subjects who are not vasectomised and who have female partners of childbearing potential and are not willing to use condoms with spermicide for a minimum of 12 weeks following the initial double-blind administration of the treatment;
15. History of alcohol or drug abuse within 5 years of the screening visit (excluding medication overuse for headache);
16. Body mass index (BMI) ≥35 kg/m² at the screening visit;
17. Known clinically significant hypersensitivity to any of the study drugs, excipients or materials used to administer the study drug;
18. Patients who, in the clinician's judgment, are actively suicidal, and therefore, deemed to be at significant risk for suicide.
19. A diagnosis of a neuromuscular disorder or respiratory disorder, such as myasthenia gravis, Lambert-Eaton syndrome or amyotrophic lateral sclerosis that in the opinion of the investigator would compromise the safety of the study participant.

Primary outcomes:
measure: Percentage of participants experiencing any Adverse Event (AEs) including treatment emergent adverse events (TEAEs), serious adverse events (SAEs), adverse event of special interest (AESI) and AE leading to treatment discontinuation
timeFrame: For step 1: From baseline until end of study at Week 36
measure: Percentage of Participants with clinically significant changes from baseline in Laboratory Parameters
timeFrame: For step 1: At all timepoints post injection until Week 36
measure: Percentage of Participants With Clinically Significant Changes from baseline in Vital Signs
timeFrame: For step 1: At all timepoints post injection until Week 36
measure: Percentage of participants with clinically significant change from baseline in facial examination
timeFrame: For step 1: At all timepoints post injection until Week 36
measure: Percentage of participants with clinically significant change from baseline in 12-lead Electrocardiogram (ECG) readings
timeFrame: For step 1: At all timepoints post injection until Week 36
measure: Treatment-emergence of suicidal ideation/suicidal behaviour
timeFrame: For step 1: At all timepoints post injection until Week 36
measure: Percentage of participants with Binding antibodies to IPN10200
timeFrame: For step 1: At baseline, Week 4, Week 12 and Week 36.
measure: Percentage of participants with neutralising antibodies to IPN10200
timeFrame: For step 1: At baseline, Week 4, Week 12 and Week 36.
measure: Change from baseline in the number of Monthly migraine days (MMD)s
timeFrame: For step 2: At Week 12 (Weeks 9-12).
Secondary outcomes:
measure: Change from baseline in the number of MMD
timeFrame: For Step 1 and step 2: From Week 1 to Week 36.
measure: Change from baseline in the number of Monthly Headache Days (MHD)
timeFrame: For Step 1 and step 2: From Week 1 to Week 36
measure: Change from baseline in the number of moderate/severe MHD
timeFrame: For Step 1 and step 2: From Week 1 to Week 36
measure: Migraine prevention response
timeFrame: For Step 1 and step 2: From Week 1 to Week 36
measure: Headache prevention response
timeFrame: For Step 1 and step 2: From Week 1 to Week 36.
measure: Change from baseline in the number of days per 4 week period of acute medication use for migraine relief.
timeFrame: For Step 1 and step 2: From Week 1 to Week 36.
measure: The use of acute migraine medication (yes or no)
timeFrame: For Step 1 and step 2: From Week 1 to Week 36.
measure: Percentage of participants with Binding antibodies to IPN10200
timeFrame: For step 2 : At baseline, Week 4, Week 12 , Week 24 and Week 36.
measure: Percentage of participants with neutralising antibodies to IPN10200
timeFrame: For step 2 : At baseline, Week 4, Week 12 , Week 24 and Week 36.
Other outcomes:
Locations:
city: Chandler
country: United States
facility: MD First Research - Chandler
state: Arizona
city: Carlsbad
country: United States
facility: Profound Research. LLC - NCSC
state: California
city: Encino
country: United States
facility: WR-PRI Encino
state: California
city: Fresno
country: United States
facility: Neuro-Pain Medical Center
state: California
city: Los Alamitos
country: United States
facility: Pharmacology Research Institute (PRI)
state: California
city: Fort Collins
country: United States
facility: Advanced Neuroscience Research Center, LLC
state: Colorado
city: Lake City
country: United States
facility: M3 Wake Research/MSRA, LLC
state: Florida
city: New Orleans
country: United States
facility: Lsu Healthcare Network
state: Louisiana
city: Baltimore
country: United States
facility: MedStar Neurosciences and Rehabilitation Research Network
state: Maryland
city: Baltimore
country: United States
facility: MedStar Neurosciences and Rehabilitation
state: Maryland
city: Ann Arbor
country: United States
facility: Michigan Head Pain & Neurological Institute
state: Michigan
city: Bronx
country: United States
facility: Montefiore Medical Center: Headache Center
state: New York
city: Brooklyn
country: United States
facility: Integrative Clinical Trials, LLC
state: New York
city: Williamsville
country: United States
facility: Upstate Clinical Research Associates
state: New York
city: Memphis
country: United States
facility: Clinical Neuroscience Solutions, Inc - Memphis
state: Tennessee
city: Tacoma
country: United States
facility: Puget Sound Neurology - Neurology
state: Washington
Study officials:
affiliation: Ipsen
name: Ipsen Medical Director
role: STUDY_DIRECTOR
References: