Clinical trial NCT06602479: A Study to Investigate the Safety and Efficacy of MEDI0618 Compared to Placebo in Adult Participants With Episodic Migraine
Official title: A Phase 2, Randomised, Multicentre, Parallel-Group Treatment, Double-Blind Study to Investigate the Safety and Efficacy of Subcutaneous MEDI0618 in the Reduction of Migraine Headache Days Compared to Placebo in Adult Participants With Episodic Migraine
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Migraine
Keywords: MEDI0618
Episodic Migraine
Migraine headache day(s) - MHD
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2024-09-19
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is parallel-group, participant and investigator blinded, treatment study. Approximately 1020 participants will be screened to achieve 408 randomised to study intervention and 366 evaluable participants.

Study Arms:

* The aCGRP-N cohort includes 5 arms (placebo and 4 active dose levels).

  * A total of 288 participants will be randomized in this cohort.
  * After 64 participants total have been randomised on a 1:1 basis to either MEDI0618 Dose A or placebo, 3 lower dose arms will be initiated and include 56 participants each. Alongside the lower dose arms, 28 participants will be concomitantly allocated to the Dose A and 28 participants to the placebo arms. At this point, an adaptive randomisation will be used to allow concurrent completion of the study for all arms.
* The aCGRP-IR cohort includes 2 arms (placebo and one active dose level). -2 arms of 60 participants each; 1 will receive MEDI0618 Dose A, and 1 will receive placebo randomised on a 1:1 basis.
Primary purpose: PREVENTION

Brief summary: The purpose of this Phase 2 study is to evaluate the safety and efficacy of SC MEDI0618 compared to placebo in participants with episodic migraine.

Detailed description: This Phase 2, randomised, multicentre, parallel-group treatment, double-blind, placebo-controlled study is designed to evaluate the safety and efficacy of SC MEDI0618 in participants with episodic migraine.

The study includes a cohort of participants who have a history of unsuccessful treatment with ≥ 3 small molecule migraine preventive treatments from different classes and are eligible to receive an aCGRP therapy (aCGRP-N); The study also includes a smaller cohort of participants who have failed one or more aCGRP therapies (aCGRP-IRs). These participants are also required to have a history of unsuccessful treatment with ≥ 3 small molecule migraine preventive treatments from different classes.

Eligibility criteria: Inclusion Criteria:

* 18 to 70 years of age
* Weight ≥ 40 kg and BMI ≥ 18.0 kg/m2.
* History of migraine headaches with or without aura, with migraine onset at ≤ 50 years of age and for at least 12 months prior to screening.
* At least 12 MHDs over the last 3 months prior to screening.
* Participants must fulfil the following criteria for migraine in prospectively collected baseline information during the 4 consecutive weeks of baseline migraine headache data collection prior to Day 1: (a) ≥ 4 and ≤ 14 MHDs per month. (b) On ≥ 4 days, fulfils any of the following criteria: (i) migraine without aura; (ii) migraine with an aura symptom accompanied or followed by a headache within 60 minutes; (iii) probable migraine; (iv) recurrent attacks that do not match ICHD criteria for migraine but successfully respond to migraine-specific medication.
* Participants who fulfil criteria for MOH are eligible for this study.
* History of unsuccessful treatment with ≥ 3 small molecule migraine preventive treatments from different classes (a) aCGRP-N participants are eligible to receive an aCGRP therapy but must have not yet received aCGRP therapy at any time. (b) aCGRP-IR participants must have tried and have failed at least one aCGRP therapy.
* Participants must be able to distinguish migraine headaches from tension-type headaches.
* Female participants who are not pregnant and do not plan to become pregnant during the study, are not lactating, or are of nonchildbearing potential. FOCBP who are sexually active with a non-sterilised male partner must use adequate contraception consisting of two highly effective methods of contraception throughout the study. FOCBP must agree to comply with protocol specified guidance for safe administration of MEDI0618.

Exclusion Criteria:

* History of migraine sub-types including hemiplegic (sporadic or familial) migraine, ophthalmoplegic migraine, and basilar-type migraine
* History of headache other than migraine within 3 months prior to screening.
* History of severe or ongoing allergy/hypersensitivity reactions or history of hypersensitivity to immunisations or immunoglobulins.
* History of any significant psychiatric disorder which could be detrimental to participant safety or could compromise study data interpretation.
* Presence of any clinically significant illness, such as cardiovascular, neurologic (except for non-exclusionary headaches in participants with migraine), pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, or endocrine disease or disorder.
* History of cancer within 5 years of screening, or between screening and randomisation, with the exception of non-metastatic basal cell carcinoma of the skin, carcinoma in situ of the cervix, or non-progressive prostate cancer.
* Known history of drug or alcohol abuse within 1 year of screening or positive test for drugs of abuse or alcohol at screening or at Day -1.
* History of QT prolongation \> 450 msec (\> 470 msec for participants aged ≥ 65 years) associated with other medications that required discontinuation of that medication.
* Congenital long or short QT syndrome.
* History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment, symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Participants with atrial fibrillation controlled by medication are permitted.
* Use of migraine preventive medications within 30 days or 5 half-lives (whichever is longer) prior to screening and throughout the study
* For aCGRP-N participants only: prior use of an aCGRP therapy.
* Use of opioids or barbiturate containing analgesic \> 2 times/month on average in the 6 months prior to screening for the treatment of pain (opioid administration in an emergency setting may be an exception).
* Use of onabotulinumtoxinA for migraine or for any other medical or cosmetic reasons requiring injections in the head, face, or neck during the 4 months prior to screening.
* Use of an intervention or device (eg, scheduled nerve block, transcranial magnetic stimulation) for treatment of migraine within 2 months of screening.
* Use of prescription or non-prescription, non-biologic drugs, including vitamins and herbal and dietary supplements, within 7 days or 5 half-lives (whichever is longer) prior to screening and throughout the study unless the medication will not interfere with the study procedures or compromise participant safety; the dose and regimen must have been stable for at least 3 months prior to screening and must remain stable throughout the study.
* Requires treatment with another biological therapeutic agent including IV immunoglobulin treatment during the course of the study. Prior use of therapeutic antibodies is allowed if that use was \> 5 half-lives of the intervention or 3 months prior to screening, whichever is longer.
* Therapeutic vaccines are permitted during the study, but ideally, live attenuated vaccines should be administered \> 30 days prior to randomisation and inactivated vaccinations (eg, inactive influenza, COVID-19) should be administered \> 14 days prior to randomisation.
* Participation in another clinical study with an IP, including an experimental vaccine, or device, within 5 half-lives of the intervention or 3 months prior to screening, whichever is longer.
* Known hypersensitivity to MEDI0618 or any of the excipients of the product.

Primary outcomes:
measure: Efficacy of repeat doses of MEDI0618 in preventing migraine headaches in patients with episodic migraine
timeFrame: Week 9 to Week 12
Secondary outcomes:
measure: Efficacy of repeat doses of MEDI0618 in preventing migraine headaches in patients with episodic migraine as proportion of patients
timeFrame: Week 9 to Week 12
measure: Effect of repeat doses of MEDI0618 on disability caused by migraine headaches
timeFrame: Day 1 to Day 84 and to Day 141
measure: Effect of repeat doses of MEDI0618 on the severity of migraine headaches
timeFrame: Week 9 to Week 12
Other outcomes:
Locations:
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country: Czechia
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city: Plzen
country: Czechia
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country: Czechia
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city: Praha 6
country: Czechia
facility: Research Site
city: Praha
country: Czechia
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city: Praha
country: Czechia
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city: Rychnov nad Kneznou
country: Czechia
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city: Glostrup
country: Denmark
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city: Berlin
country: Germany
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city: Chemnitz
country: Germany
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city: Dresden
country: Germany
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city: Essen
country: Germany
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city: Frankfurt am Main
country: Germany
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city: Munich
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city: Budapest
country: Hungary
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city: Budapest
country: Hungary
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city: Dunaujvaros
country: Hungary
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city: Milano
country: Italy
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city: Pavia
country: Italy
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city: Roma
country: Italy
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country: Italy
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city: Leiden
country: Netherlands
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country: Poland
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country: Poland
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country: Poland
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country: Poland
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city: Lublin
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country: Poland
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city: Poznań
country: Poland
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city: Warszawa
country: Poland
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city: Warszawa
country: Poland
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city: Warszawa
country: Poland
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city: Badajoz
country: Spain
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city: Barcelona
country: Spain
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city: Barcelona
country: Spain
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city: Madrid
country: Spain
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city: Valencia
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
Study officials:
References: