Chronic Migraine, HeadachePhase 4COACTNCT05724771
COACT Study: CGRPmAbs + OnabotulinumtoxinA Assessment of Chronic Migraine Treatments Study
A Phase 4 study testing Combination of Botox + CGRPmAb (Fremanezumab 225mg/1.5mL) in people with Chronic Migraine, Headache, run by Chicago Headache Center & Research Institute at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Chronic Migraine, Headache
- What is being tested?
- Combination of Botox + CGRPmAb (Fremanezumab 225mg/1.5mL)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Jan 2023to May 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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))
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Chicago Headache Center & Research Institute
Chicago, Illinois, 60657
About this study
Official title: Assessing the Safety and Efficacy of Utilizing CGRPmAb Fremanezumab (Ajovy) in Chronic Migraine Patients Currently on Monotherapy OnabotulinumtoxinA (Botox).
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.
Read the 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.
- Conditions
- Chronic Migraine, Headache
- Being tested
- Combination of Botox + CGRPmAb (Fremanezumab 225mg/1.5mL)
- Medical subject headings
- Headache
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Combination of Botox + CGRPmAb (Fremanezumab 225mg/1.5mL)Drug
OnabotulinumtoxinA + Fremanezumab 225mg/1.5mL
| Study group | Role | What they receive |
|---|---|---|
| Combination of Botox + CGRPmAb | Experimental | OnabotulinumtoxinA + Fremanezumab 225mg/1.5mL = 50 Receives: Drug: Combination of Botox + CGRPmAb (Fremanezumab 225mg/1.5mL) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in number of monthly migraine days with the addition of CGRPmAb Fremanezumab in chronic migraine patients currently on monotherapy OnabotulinumtoxinA.
Change in number of monthly migraine days from baseline.
Measured: 6 months
Secondary outcomes (1)
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.
Change in HIT-6 (Headache Impact Test) assessment score from baseline.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2023
- Study start26 Jan 2023
- Primary completionMar 2025 (estimated)
- Study completionMay 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Chronic Migraine, HeadacheStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model 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.
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chicago Headache Center & Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Bradley Torphy, MD, Chicago Headache Center & Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05724771
- Sponsor's protocol ID
- 2020-01
- Acronym
- COACT
- Status last verified
- Aug 2024
- First submitted
- 18 Jan 2023
- Last updated
- 20 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Goadsby PJ, Reuter U, Hallstrom Y, Broessner G, Bonner JH, Zhang F, Sapra S, Picard H, Mikol DD, Lenz RA. A Controlled Trial of Erenumab for Episodic Migraine. N Engl J Med. 2017 Nov 30;377(22):2123-2132. doi: 10.1056/NEJMoa1705848.
PubMed 29171821Dodick DW, Ashina M, Brandes JL, Kudrow D, Lanteri-Minet M, Osipova V, Palmer K, Picard H, Mikol DD, Lenz RA. ARISE: A Phase 3 randomized trial of erenumab for episodic migraine. Cephalalgia. 2018 May;38(6):1026-1037. doi: 10.1177/0333102418759786. Epub 2018 Feb 22.
PubMed 29471679Stauffer VL, Dodick DW, Zhang Q, Carter JN, Ailani J, Conley RR. Evaluation of Galcanezumab for the Prevention of Episodic Migraine: The EVOLVE-1 Randomized Clinical Trial. JAMA Neurol. 2018 Sep 1;75(9):1080-1088. doi: 10.1001/jamaneurol.2018.1212.
PubMed 29813147Skljarevski V, Matharu M, Millen BA, Ossipov MH, Kim BK, Yang JY. Efficacy and safety of galcanezumab for the prevention of episodic migraine: Results of the EVOLVE-2 Phase 3 randomized controlled clinical trial. Cephalalgia. 2018 Jul;38(8):1442-1454. doi: 10.1177/0333102418779543. Epub 2018 May 31.
PubMed 29848108Dodick DW, Silberstein SD, Bigal ME, Yeung PP, Goadsby PJ, Blankenbiller T, Grozinski-Wolff M, Yang R, Ma Y, Aycardi E. Effect of Fremanezumab Compared With Placebo for Prevention of Episodic Migraine: A Randomized Clinical Trial. JAMA. 2018 May 15;319(19):1999-2008. doi: 10.1001/jama.2018.4853.
PubMed 29800211Ferrari MD, Diener HC, Ning X, Galic M, Cohen JM, Yang R, Mueller M, Ahn AH, Schwartz YC, Grozinski-Wolff M, Janka L, Ashina M. Fremanezumab versus placebo for migraine prevention in patients with documented failure to up to four migraine preventive medication classes (FOCUS): a randomised, double-blind, placebo-controlled, phase 3b trial. Lancet. 2019 Sep 21;394(10203):1030-1040. doi: 10.1016/S0140-6736(19)31946-4. Epub 2019 Aug 16.
PubMed 31427046Blumenfeld AM, Frishberg BM, Schim JD, Iannone A, Schneider G, Yedigarova L, Manack Adams A. Real-World Evidence for Control of Chronic Migraine Patients Receiving CGRP Monoclonal Antibody Therapy Added to OnabotulinumtoxinA: A Retrospective Chart Review. Pain Ther. 2021 Dec;10(2):809-826. doi: 10.1007/s40122-021-00264-x. Epub 2021 Apr 21.
PubMed 33880725
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessing the Safety and Efficacy of Utilizing CGRPmAb Fremanezumab (Ajovy) in Chronic Migraine Patients Currently on Monotherapy OnabotulinumtoxinA (Botox).
- ClinicalTrials.gov ID
- NCT05724771
- Acronym / sponsor ID
- COACT / 2020-01
- Conditions
- Chronic Migraine, Headache
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Chicago Headache Center & Research InstituteUniversity, hospital or other
- Study start
- 26 Jan 2023 (actual)
- Primary completion
- Mar 2025 (estimated)
- Study completion
- May 2025 (estimated)
- First posted
- 13 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model 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.
| Arm | Type | Receives |
|---|---|---|
| Combination of Botox + CGRPmAb | Experimental | Drug: Combination of Botox + CGRPmAb (Fremanezumab 225mg/1.5mL)OnabotulinumtoxinA + Fremanezumab 225mg/1.5mL = 50 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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):
- History of ≥8 monthly migraine days (average from 3 previous months prior to enrollment (visit 2))
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Combination of Botox + CGRPmAb (Fremanezumab 225mg/1.5mL)OnabotulinumtoxinA + Fremanezumab 225mg/1.5mL | Drug | Combination of Botox + CGRPmAb |
Primary outcome
Change in number of monthly migraine days with the addition of CGRPmAb Fremanezumab in chronic migraine patients currently on monotherapy OnabotulinumtoxinA.
Time frame: 6 months
Change in number of monthly migraine days from baseline.
1 secondary outcome
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.
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2024.
- Background: PubMed 29171821Goadsby PJ, Reuter U, Hallstrom Y, Broessner G, Bonner JH, Zhang F, Sapra S, Picard H, Mikol DD, Lenz RA. A Controlled Trial of Erenumab for Episodic Migraine. N Engl J Med. 2017 Nov 30;377(22):2123-2132. doi: 10.1056/NEJMoa1705848.
- Background: PubMed 29471679Dodick DW, Ashina M, Brandes JL, Kudrow D, Lanteri-Minet M, Osipova V, Palmer K, Picard H, Mikol DD, Lenz RA. ARISE: A Phase 3 randomized trial of erenumab for episodic migraine. Cephalalgia. 2018 May;38(6):1026-1037. doi: 10.1177/0333102418759786. Epub 2018 Feb 22.
- Background: PubMed 29813147Stauffer VL, Dodick DW, Zhang Q, Carter JN, Ailani J, Conley RR. Evaluation of Galcanezumab for the Prevention of Episodic Migraine: The EVOLVE-1 Randomized Clinical Trial. JAMA Neurol. 2018 Sep 1;75(9):1080-1088. doi: 10.1001/jamaneurol.2018.1212.
- Background: PubMed 29848108Skljarevski V, Matharu M, Millen BA, Ossipov MH, Kim BK, Yang JY. Efficacy and safety of galcanezumab for the prevention of episodic migraine: Results of the EVOLVE-2 Phase 3 randomized controlled clinical trial. Cephalalgia. 2018 Jul;38(8):1442-1454. doi: 10.1177/0333102418779543. Epub 2018 May 31.
- Background: PubMed 29800211Dodick DW, Silberstein SD, Bigal ME, Yeung PP, Goadsby PJ, Blankenbiller T, Grozinski-Wolff M, Yang R, Ma Y, Aycardi E. Effect of Fremanezumab Compared With Placebo for Prevention of Episodic Migraine: A Randomized Clinical Trial. JAMA. 2018 May 15;319(19):1999-2008. doi: 10.1001/jama.2018.4853.
- Background: PubMed 31427046Ferrari MD, Diener HC, Ning X, Galic M, Cohen JM, Yang R, Mueller M, Ahn AH, Schwartz YC, Grozinski-Wolff M, Janka L, Ashina M. Fremanezumab versus placebo for migraine prevention in patients with documented failure to up to four migraine preventive medication classes (FOCUS): a randomised, double-blind, placebo-controlled, phase 3b trial. Lancet. 2019 Sep 21;394(10203):1030-1040. doi: 10.1016/S0140-6736(19)31946-4. Epub 2019 Aug 16.
- Background: PubMed 33880725Blumenfeld AM, Frishberg BM, Schim JD, Iannone A, Schneider G, Yedigarova L, Manack Adams A. Real-World Evidence for Control of Chronic Migraine Patients Receiving CGRP Monoclonal Antibody Therapy Added to OnabotulinumtoxinA: A Retrospective Chart Review. Pain Ther. 2021 Dec;10(2):809-826. doi: 10.1007/s40122-021-00264-x. Epub 2021 Apr 21.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Combination of Botox + CGRPmAb (Fremanezumab 225mg/1.5mL) in people with Chronic Migraine, Headache, run by Chicago Headache Center & Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 20 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in number of monthly migraine days with the addition of CGRPmAb Fremanezumab in chronic migraine patients currently on monotherapy OnabotulinumtoxinA. (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05724771, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2024.