COACT Study: CGRPmAbs + OnabotulinumtoxinA Assessment of Chronic Migraine Treatments Study

Phase 4

Active, not recruiting

• Conditions: Chronic Migraine, Headache
• Interventions: Drug: Combination of Botox + CGRPmAb (Fremanezumab 225mg/1.5mL)

• Registration Number: NCT05724771
• Lead Sponsor: Chicago Headache Center & Research Institute

Brief Summary

Chronic migraine patients treated with OnabotulinumtoxinA may experience breakthrough headaches, especially toward the end of their 12-week therapy. The addition of a CGRPmAb could help in decreasing or eliminating these episodes, but this combination is considered "experimental" by many payers, which often leads to a denial of coverage. Currently, there is no reference in the literature or data to support the treatment of chronic migraine with OnabotulinumtoxinA and CGRPmAbs (Aimovig, Ajovy, Emgality or Vyepti) combination therapy. This has resulted in many patients and providers having to settle for one or the other. Investigators hopes to provide crucial data and findings to support the addition of CGRPmAb in some chronic migraine patients currently on monotherapy OnabotulinumtoxinA.

Detailed Description

Phase IV prospective open label interventional clinical study evaluating beneficial outcomes of the addition of CGRPmAb Fremanezumab in chronic migraine patients currently on monotherapy OnabotulinumtoxinA.

The investigators will enroll patients with ≥2 OnabotulinumtoxinA treatments at screening with a history of ≥8 monthly migraine days (average from 3 previous months prior to enrollment (visit 2)). Between visit 1 (screening) and visit 3, all patients will be on monotherapy OnabotulinumtoxinA for up to 12 weeks.

Patients will be administered a total of 2 OnabotulinumtoxinA treatments for the duration of the entire study. OnabotulinumtoxinA treatment will be administered at Day 1 (visit 2) and Day 90 (visit 4), with a treatment window ±6 days.

OnabotulinumtoxinA treatment of 155 units or 195 units will be injected intramuscularly over 31-35 injections of head and neck muscles. Study patients must be on a stable OnabotulinumtoxinA dose at screening (visit 1), that dose will be used for the duration of the study.

Dosing paradigm:

At Day 7 (visit 3) study patients will initiate CGRPmAbs treatment of Fremanezumab 225mg/1.5mL monthly dose for 6 months. Doses will be taken on Days: 7, 37, 67, 97, 127, and 157; with a treatment window ±2 days.

• OnabotulinumtoxinA + Fremanezumab 225mg/1.5mL = 50 Rescue medication will be allowed to treat acute migraine attacks consistent with the parameters referenced in previous CGRP clinical trials.

Acute rescue utilizing -gepants will be limited to no more than 5 days per month.

No use of -gepants as a preventative treatment for at least 1 week prior to screening (visit 1) and throughout the duration of the study.

Study Timeline

• Study First Submitted: 2023-01-18
• Study Start: 2023-01-26
• Study First Submitted QC: 2023-02-02
• Study First Posted: 2023-02-13
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-19
• Last Update Posted: 2024-08-20
• Primary Completion: 2025-03
• Study Completion: 2025-05

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• Chronic migraine patients between 18 to 75 years old

• Chronic migraine patients with ≥ 12-month history of migraine

• Participant has received at least 2 consecutive OnabotulinumtoxinA treatment at screening (visit 1)

• Achieved a clinically appropriate response from monotherapy OnabotulinumtoxinA at enrollment (visit 2):

  • ≥50% reduction in mean monthly headache days of at least moderate severity OR Reduction of ≥7 mean monthly headache days of at least moderate severity OR
  • HIT-6 reduction of ≥5 points

• History of ≥8 monthly migraine days (average from 3 previous months prior to enrollment (visit 2))

Exclusion Criteria

• History of <8 monthly migraine days (average from 3 previous months prior to enrollment (visit 2))
• Patients with current use, or use within 3 months prior to screening (visit 1) a CGRPmAbs (Aimovig, Ajovy, Emgality, or Vyepti)
• Concomitant use of gepants as a preventative treatment < 1 week prior to screening (visit 1).
• Utilizing gepants as an acute rescue treatment >5 days per month.
• Current user of recreational or illicit drugs, or a history within 1 year prior to screening (visit 1) of drug or alcohol abuse or dependence
• Clinically significant hematologic, endocrine, cardiovascular, pulmonary, gastrointestinal, or neurologic disease. If there is a history of such a disease, but the condition has been stable for more than 1 year prior to screening (visit 1) and is judged by the PI as not likely to interfere with participation in the study, the participant may be included.
• Female is pregnant, planning to become pregnant during the course of the study, or currently lactating.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Combination of Botox + CGRPmAb	Combination of Botox + CGRPmAb (Fremanezumab 225mg/1.5mL)	OnabotulinumtoxinA + Fremanezumab 225mg/1.5mL = 50

Primary Outcome Measures

Name	Time	Method
Change in number of monthly migraine days with the addition of CGRPmAb Fremanezumab in chronic migraine patients currently on monotherapy OnabotulinumtoxinA.	6 months	Change in number of monthly migraine days from baseline.

Secondary Outcome Measures

Name	Time	Method
To assess improvements in HIT-6 (Headache Impact Test) score of >5 point reduction with the addition of CGRPmAb Fremanezumab in chronic migraine patients currently on monotherapy OnabotulinumtoxinA.	6 months	Change in HIT-6 (Headache Impact Test) assessment score from baseline.

Trial Locations

Locations (1)

Chicago Headache Center & Research Institute; 🇺🇸 Chicago, Illinois, United States