A Study to Investigate the Safety and Efficacy of MEDI0618 Compared to Placebo in Adult Participants With Episodic Migraine
- Registration Number
- NCT06602479
- Lead Sponsor
- AstraZeneca
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 12
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description CGRP-N_MEDI0618 (Dose A) MEDI0618 In the CGRP-N cohort, there will be 1:1 randomisation to the MEDI0618 and placebo arms until 32 participants have been randomised per arm (32 MEDI0618 Dose A and 32 to placebo) triggering the interim analysis. After 32 participants/arm have been randomised, the randomization will continue with 28 participants on active dose arm. CGRP-N_MEDI0618 (Dose C) MEDI0618 After 32 participants/arm have been randomized in the Dose A and placebo arms, the randomization will continue with 56 participants on active dose arm. CGRP-N_MEDI0618 (Dose B) MEDI0618 After 32 participants/arm have been randomized in the Dose A and placebo arms, the randomization will continue with 56 participants on active dose arm. CGRP-N_MEDI0618 (Dose D) MEDI0618 After 32 participants/arm have been randomized in the Dose A and placebo arms, the randomization will continue with 56 participants on active dose arm. CGRP-IR_MEDI0618 (Dose A) MEDI0618 In the CGRP-IR cohort there will be 1:1 randomisation of participants to the two arms (60 to MEDI0618 and 60 to placebo) . CGRP-N_Placebo Placebo In the CGRP-N cohort, there will be 1:1 randomisation to the MEDI0618 Dose A and placebo arms until 32 participants have been randomised per arm (32 to MEDI0618 Dose A and 32 to placebo) triggering the interim analysis. After 32 participants/arm have been randomised, the randomization will continue with 28 participants with corresponding volume matched placebo for all arms. CGRP-IR_Placebo Placebo In the CGRP-IR cohort there will be 1:1 randomisation of participants to the two arms (60 to MEDI0618 and 60 to placebo).
- Primary Outcome Measures
Name Time Method Efficacy of repeat doses of MEDI0618 in preventing migraine headaches in patients with episodic migraine Week 9 to Week 12 Change in number of MHDs from 4-week baseline to last 4 weeks of treatment period.
- Secondary Outcome Measures
Name Time Method Efficacy of repeat doses of MEDI0618 in preventing migraine headaches in patients with episodic migraine as proportion of patients Week 9 to Week 12 Participants with at least 50% reduction in number of MHDs in the last 4 weeks of treatment period compared to 4-week baseline.
Effect of repeat doses of MEDI0618 on disability caused by migraine headaches Day 1 to Day 84 and to Day 141 Change in MIDAS score from baseline to end of treatment period and to follow-up.
Effect of repeat doses of MEDI0618 on the severity of migraine headaches Week 9 to Week 12 Change in number of moderate or severe MHDs from 4-week baseline to last 4 weeks of treatment period.
Change in number of moderate or severe headache days from 4-week baseline to last 4 weeks of treatment period.
Change in frequency of use of permitted acute treatment to abort migraine headaches from 4-week baseline to last 4 weeks of the treatment period.
Trial Locations
- Locations (1)
Research Site
🇪🇸Valencia, Spain