Safety and Efficacy of Fremanezumab for Migraine in Adult CADASIL

• ClinicalTrials.gov Identifier: NCT04334408
• Recruitment Status: Withdrawn
• First Posted: April 6, 2020
• Last Update Posted: February 28, 2022
• Sponsor: Mayo Clinic
• Information provided by (Responsible Party): James F. Meschia, Mayo Clinic

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cadasil; Migraine	Drug: Fremanezumab; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Estimated Study Start Date: December 2021
• Estimated Primary Completion Date: December 2024
• Estimated Study Completion Date: December 2024

Arms and Interventions

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 Name: 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 Name: 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.

Outcome Measures

Primary Outcome Measures :

1. Change in migraine-related disability [ Time Frame: Baseline, 2 week intervals up to 48 weeks ]
   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
2. Change in headache intensity [ Time Frame: Baseline, 2 week intervals up to 48 weeks ]
   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.
3. Adverse events [ Time Frame: 48 weeks ]
   Number of adverse events reported

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Sponsors and Collaborators

Mayo Clinic

Investigators

• Principal Investigator: James F Meschia; Mayo Clinic

More Information

Additional Information:

Mayo Clinic Clinical Trials 

• Responsible Party: James F. Meschia, Principal Investigator, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT04334408
• Other Study ID Numbers: 18-010786
• First Posted: April 6, 2020
• Last Update Posted: February 28, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Migraine Disorders; CADASIL; Dementia, Multi-Infarct; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Infarction; Brain Infarction; Brain Ischemia; Cerebrovascular Disorders; Cerebral Small Vessel Diseases; Dementia, Vascular; Cerebral Arterial Diseases; Intracranial Arterial Diseases; Stroke; Dementia; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Infarction; Ischemia; Pathologic Processes; Necrosis; Neurocognitive Disorders; Mental Disorders