Safety and Efficacy of Fremanezumab for Migraine in Adult CADASIL

A Phase II Double-Blinded Placebo Controlled Individual Subject Stepped Wedge Clinical Trial Evaluating the Safety and Efficacy of Fremanezumab for Migraine in Adult CADASIL

Researchers are trying to find out more about the side effects of fremanezumab when treating patients with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) for migraine headaches.

Study Overview

• Status: Withdrawn
• Conditions: Migraine; Cadasil
• Intervention / Treatment: Drug: Fremanezumab; Drug: Placebo

Detailed Description

Subjects will receive 4 to 20 weeks of placebo injections followed by 12 weeks of monthly administered fremanezumab by subcutaneous injection (225 mg split four weeks apart for 12 weeks). Following completion of the 12 weeks of therapy, the participant will return to placebo for the washout period. Both the patient and the investigator will be blinded to the timing of transition to and from placebo and the transition to and from fremanezumab.

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• Age 18 to 70 years old
• English speaking
• Diagnosis of CADASIL confirmed by presence of a pathogenic NOTCH3 gene mutation
• Diagnosis of migraine for at least 12 months and diagnosis of chronic migraine for at least 28 days according to the International Classification of Headache Disorders
• MIDAS score of >10 points
• Ability to provide written informed consent

Exclusion Criteria

• History of ischemic stroke within 4 weeks of screening assessment
• Screening blood pressure >150 mm Hg
• Use of onabotulinum toxin A 4 months prior to trial or other injectable/stimulatory/magnetic method of headache control
• Use of opiates or barbiturates 4 days prior to trial
• Patients with competing intracerebral pathology (e.g. history of intracerebral hemorrhage, multiple sclerosis)
• NYHA Class III or IV congestive heart failure
• History of myocardial infarction
• History of coronary bypass surgery or coronary stenting
• Pregnancy or breastfeeding
• Contraindication to undergoing brain MRI per standard clinical practice guidelines
• Vulnerable populations, including incarcerated inmates, dementia, and inability to provide consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Subjects with CADASIL treatment intervention; Subjects that have been diagnosed with both CADASIL and moderately to severely disabling migraine headaches will be treated with Fremanezumab injections.	Drug: Fremanezumab; Subjects will receive a single dose total 225 mg (1 injection of 225 mg per 1.5 mL injection) followed by a single dose of 225 mg (1 1.5mL injection) at four week intervals. Both the subject and the investigator will be blinded to the timing of transition to and from placebo and the transition to and from fremanezumab.; Other Names: Ajovy; Drug: Placebo; Placebo injections during the run in and washout serves as the control condition. Both the subject and the investigator will be blinded to the timing of transition to and from placebo and the transition to and from fremanezumab.
Placebo Comparator: Subjects with CADASIL placebo intervention; Subjects that have been diagnosed with both CADASIL and moderately to severely disabling migraine headaches will be treated with placebo injections.	Drug: Fremanezumab; Subjects will receive a single dose total 225 mg (1 injection of 225 mg per 1.5 mL injection) followed by a single dose of 225 mg (1 1.5mL injection) at four week intervals. Both the subject and the investigator will be blinded to the timing of transition to and from placebo and the transition to and from fremanezumab.; Other Names: Ajovy; Drug: Placebo; Placebo injections during the run in and washout serves as the control condition. Both the subject and the investigator will be blinded to the timing of transition to and from placebo and the transition to and from fremanezumab.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in migraine-related disability	Measured using the The Migraine Disability Assessment (MIDAS) questionnaire which is a brief, self-administered questionnaire designed to quantify headache-related disability over a 3 month period using number of days	Baseline, 2 week intervals up to 48 weeks
Change in headache intensity	Measured using Headache Impact Test (HIT)-6 scores with the answers being never, rarely, sometimes, very often or always and equating to 6, 8, 10, 11, and 13 points respectively. Each answer is summated to equal the final score.	Baseline, 2 week intervals up to 48 weeks
Adverse events	Number of adverse events reported	48 weeks

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: James F Meschia, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2021
• Primary Completion (Anticipated): December 1, 2024
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: April 2, 2020
• First Submitted That Met QC Criteria: April 2, 2020
• First Posted (Actual): April 6, 2020

Study Record Updates

• Last Update Posted (Actual): February 28, 2022
• Last Update Submitted That Met QC Criteria: February 14, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Ischemia; Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Genetic Diseases, Inborn; Brain Ischemia; Dementia; Infarction; Headache Disorders, Primary; Headache Disorders; Stroke; Brain Infarction; Cerebral Arterial Diseases; Intracranial Arterial Diseases; Cerebral Small Vessel Diseases; Cerebral Infarction; Dementia, Vascular; Migraine Disorders; CADASIL; Dementia, Multi-Infarct
• Other Study ID Numbers: 18-010786

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No