Safety and Efficacy of Fremanezumab for Migraine in Adult CADASIL

Sponsor

Mayo Clinic (Other)

Overall Status

Withdrawn

CT.gov ID

NCT04334408

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

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

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

Anticipated Study Start Date :

Dec 1, 2021

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Dec 1, 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 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.

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

Other Names:

Ajovy

Drug: Placebo

Outcome Measures

Primary Outcome Measures

Change in migraine-related disability [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
Change in headache intensity [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.
Adverse events [48 weeks]
Number of adverse events reported

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

No locations specified.

Sponsors and Collaborators

Mayo Clinic

Investigators

Principal Investigator: James F Meschia, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Mayo Clinic Clinical Trials

Publications

None provided.

Responsible Party:

James F. Meschia, Principal Investigator, Mayo Clinic

ClinicalTrials.gov Identifier:

NCT04334408

Other Study ID Numbers:

18-010786

First Posted:

Apr 6, 2020

Last Update Posted:

Feb 28, 2022

Last Verified:

Feb 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Migraine Disorders

CADASIL

Dementia, Multi-Infarct

Study Results

No Results Posted as of Feb 28, 2022