Clinical trial NCT06047457: A Study to Evaluate the Effectiveness and Safety of Dysport® for the Prevention of Episodic Migraine in Adults
Official title: A Phase III, Randomised, Double-blind, Placebo-controlled, Multicenter, Parallel-group Study With Extension Phase to Evaluate the Efficacy and Safety of Dysport® for the Prevention of Episodic Migraine in Adult Participants
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Episodic Migraine
Lead sponsor: Ipsen
Sponsor class: INDUSTRY
First posted: 2023-09-21
Enrollment: 714
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to understand the safety and effectiveness of the study drug, Dysport® when compared with placebo in preventing episodic migraine.

A migraine is a headache with severe throbbing pain or a pulsating sensation, usually on one side of the head, and is often accompanied by feeling or being sick and a sensitivity to bright lights and sound.

Episodic Migraine is defined as having less than 15 days of headache a month with at least 6 days with migraine headaches.

Migraines are caused by a series of events which cause the brain to get stimulated / activated, which results in the release of chemicals that cause pain.

Dysport® is a formulation of Botulinum toxin type A (BoNT-A), a medication that stops the release of these chemical messengers.

The study will consist of 3 periods:

1. A 'screening period' of 6 to 12 weeks to assess whether the participant can take part to the study and requires 1 visit.
2. A first Treatment Phase of 24 weeks. On Day 1 and at Week 12 of the first Treatment Phase, participants will receive injections into various muscles across the head, neck, face and shoulders.

   The injections will contain either a dose "A" or a dose ''B'' of Dysport® or a placebo (an inactive substance or treatment that looks the same as, and is given in the same way as, an active drug or intervention/treatment being studied).

   Participants will make 4 visits to the clinic in person and have 4 remote (online) visits.
3. A second Treatment Phase of 24 weeks (extension phase). At Week 24 and at Week 36, all participants will get Dysport® (dose "A" or dose "B").

There will be 3 in person visits and 4 remote visits.

Participants will need to complete an e-diary and questionnaires throughout the study.

Participants will undergo blood samplings, urine collections, physical examinations, and clinical evaluations. They may continue some other medications, but the details need to be recorded.

The total study duration for a participant will be up to 60 weeks (approx. 14 months).


Eligibility criteria: Inclusion Criteria :

* must be ≥18 years of age inclusive, at the time of signing the informed consent and privacy/data protection documentation.
* Participant has a diagnosis for more than 12 months, prior to screening visit, of migraine with aura or migraine without aura according to the International Classification of Headache Disorders definition and diagnostic criteria
* Migraine onset occurred when participant was \<50 years of age.
* Has baseline number of monthly headache days (MHD) of \<15 and baseline number of monthly migraine days (MMD) of ≥6, using eDiary data collected during the 4 weeks nearest to randomisation on Day 1 (but prior to randomisation).
* Has baseline number of valid diary days ≥22 days collected during the 4 weeks nearest to randomisation on Day 1.
* Participant must have previously used, or is currently using, preventive treatment for migraine (pharmacological) (i.e. non-naïve) prior to start of screening eDiary

Exclusion Criteria :

* History or current diagnosis of migraine with brainstem aura, retinal migraine, complications of migraine, tension-type headache, trigeminal autonomic cephalalgias, hypnic headache, hemicrania continua, or new daily persistent headache.
* Headache attributed to another disorder (e.g. secondary headaches), except medication overuse headache, which is permitted.
* Use of any of the following medications in the specified timeframe prior to start of the screening daily headache eDiary:

  * a. Within 24 weeks

    * i. Botulinum toxin for migraine (or for any other medical/aesthetic reason within 16 weeks)
  * b. Within 12 weeks

    * i. CGRP antagonists (monoclonal antibody or gepant) for preventive treatment of migraine (acute treatment of headache/migraine with a gepant is permitted, but limited to no more than 6 days per month (i.e. 6 days per each 4-week period with gepant intake))
    * ii. Cannabinol or other types of cannabinoids
  * c. Within 4 weeks

    * i. Anaesthetic or steroid injection in any region targeted for injection with study intervention
    * ii. Use of medical device to treat migraine (e.g. non-invasive neuromodulation therapies such as nerve stimulation (gammaCore), transcranial magnetic stimulation (cephaly), external trigeminal nerve stimulation, transcutaneous electrical nerve stimulation, and peripheral neuroelectrical stimulation)
    * iii. Other interventions for migraine assessed to interfere with study evaluations (e.g. acupuncture in head and neck region, cranial traction, nociceptive trigeminal inhibition, occipital nerve block treatments, and dental splints for headache) iv. Use of opioids or barbiturates for more than 2 days/month.

Note: participants are permitted to take one concomitant migraine preventative treatment (not listed above); however, the dose of this medication should be stable for ≥3 months before start of the screening eDiary.

• Known history of treatment failure to more than four medications prescribed for the prevention of migraine (two of which have different mechanisms of action) or known history of treatment failure to botulinum toxin prescribed for the prevention of migraine.

Primary outcomes:
measure: Change from baseline in monthly migraine days (MMD)
timeFrame: Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24)
Secondary outcomes:
measure: Change from baseline in MMD of ≥50%
timeFrame: Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24)
measure: Change from baseline in MMD of ≥75%
timeFrame: Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24)
measure: Cumulative number of MMD
timeFrame: From Day 1 to Week 24
measure: Change from baseline in MMD of moderate or severe intensity
timeFrame: Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24)
measure: Change from baseline in monthly headache days (MHD) of moderate or severe intensity
timeFrame: Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24)
measure: Change from baseline in MHD of moderate or severe intensity of ≥50%
timeFrame: Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24)
measure: Change from baseline in MHD of moderate or severe intensity of ≥75%
timeFrame: Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24)
measure: Cumulative number of MHD of moderate to severe intensity
timeFrame: From Day 1 to Week 24
measure: Change from baseline in the number of days per month of acute migraine medication intake
timeFrame: Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24)
measure: Headache medication overuser (yes, no)
timeFrame: Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24)
measure: Use of acute migraine medication (yes or no)
timeFrame: Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24)
measure: Patient's Global Impression of Change (PGIC) score
timeFrame: At Week 12 and Week 24
measure: Change from baseline of ≥1 and ≥2 grades in PGIC score
timeFrame: At Week 12 and Week 24
measure: Change from baseline in role function restrictive domain of Migraine Specific Quality of Life Questionnaire (MSQ)
timeFrame: At Week 12 and Week 24
measure: Change from baseline in total MSQ score
timeFrame: At Week 12 and Week 24
measure: Change in MSQ score to the minimally important difference/change (MID/MIC)
timeFrame: At Week 12 and Week 24
measure: Change from baseline in total 6-item Headache Impact Test (HIT-6) score
timeFrame: At Week 12 and Week 24
measure: Change in total 6-item Headache Impact Text (HIT-6) score to the minimally important difference/change (MID/MIC)
timeFrame: At Week 12 and Week 24
measure: Change from baseline in Short Form 12 (SF-12) Questionnaire score
timeFrame: At Week 12 and Week 24
measure: Change from baseline to Chronic migraine status
timeFrame: At Week 24 (Week 21-24)
measure: Time to onset of effect
timeFrame: From first time point post randomisation to Week 24
measure: Incidence of Treatment emergent adverse event (TEAEs)
timeFrame: Up to Week 24
measure: Percentage of Participants with clinically significant changes in vital signs
timeFrame: From baseline up to Week 24
measure: Percentage of participants with clinically significant laboratory parameters (blood chemistry, haematology)
timeFrame: From baseline up to Week 24
measure: Treatment-emergence of suicidal ideation/suicidal behaviour
timeFrame: From baseline up to Week 24
measure: Percentage of participants with Binding antibodies to Dysport®
timeFrame: At Week 24
measure: Percentage of participants with neutralising antibodies to Dysport®
timeFrame: At Week 24
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Central Research Associates
state: Alabama
city: Phoenix
country: United States
facility: CCT Research
state: Arizona
city: Scottsdale
country: United States
facility: HonorHealth Neurology
state: Arizona
city: Tempe
country: United States
facility: Alliance for Multispecialty Research (AMR) Phoenix
state: Arizona
city: Canoga Park
country: United States
facility: Hope Clinical Research, LLC
state: California
city: Colton
country: United States
facility: Axiom Research LLC
state: California
city: Fullerton
country: United States
facility: Fullerton Neurological Center
state: California
city: Fullerton
country: United States
facility: Neurology Center of North Orange County
state: California
city: Orange
country: United States
facility: SDS Clinical Trials
state: California
city: San Diego
country: United States
facility: Alliance Clinical San Diego (Acclaim Clinical Research)
state: California
city: Savannah
country: United States
facility: The Los Angeles Headache Center
state: California
city: New Haven
country: United States
facility: Hasbani Neurology
state: Connecticut
city: Aventura
country: United States
facility: Visionary Investigators Network (VIN)
state: Florida
city: Hallandale Beach
country: United States
facility: Velocity Clinical Research - Hallandale Beach
state: Florida
city: Hialeah
country: United States
facility: AGA Clinical Trials
state: Florida
city: Hollywood
country: United States
facility: Infinity Clinical Research, LLC
state: Florida
city: Jacksonville
country: United States
facility: Clinical Neuroscience Solutions Healthcare, Inc (CNS Healthcare, INC)
state: Florida
city: Miami Beach
country: United States
facility: Quantum Clinical Trials
state: Florida
city: Miami
country: United States
facility: 840042
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions, Inc ((CNS Healthcare) - Psychiatry)
state: Florida
city: Tampa
country: United States
facility: Guardian Angel Research Center
state: Florida
city: Winter Haven
country: United States
facility: Clinical Research of Central Florida (also known as Bon Clinic)
state: Florida
city: Winter Park
country: United States
facility: Boston Clinical Trials Inc
state: Florida
city: Winter Park
country: United States
facility: Conquest Research
state: Florida
city: Decatur
country: United States
facility: CenExel iResearch Atlanta, LLC
state: Georgia
city: Savannah
country: United States
facility: Velocity Clinical Research, Savanah
state: Georgia
city: Chicago
country: United States
facility: Cedar Crosse Research Center
state: Illinois
city: Chicago
country: United States
facility: Chicago Headache Center & Research Institute
state: Illinois
city: Riverwoods
country: United States
facility: Robbins Headache Clinic
state: Illinois
city: Fort Wayne
country: United States
facility: MD Fort Wayne Neurological Center
state: Indiana
city: Frederick
country: United States
facility: Comprehensive Neurology Services
state: Maryland
city: Boston
country: United States
facility: Boston Clinical Trials Inc
state: Massachusetts
city: Brookline
country: United States
facility: Beth Israel Deaconess Medical Center - Arnold Pain Management
state: Massachusetts
city: Foxboro
country: United States
facility: Neurology Center of NE,PC - Neurology
state: Massachusetts
city: Westborough
country: United States
facility: Lone Star Neurology,
state: Massachusetts
city: Worcester
country: United States
facility: New England Regional Headache Center, Inc.
state: Massachusetts
city: Farmington Hills
country: United States
facility: Quest Research Institute
state: Michigan
city: Burnsville
country: United States
facility: Minneapolis Clinic of Neurology
state: Minnesota
city: Chesterfield
country: United States
facility: Clinical Research Professionals
state: Missouri
city: Las Vegas
country: United States
facility: M3 Wake Research - Las Vegas Wellness Way
state: Nevada
city: Las Vegas
country: United States
facility: Alliance Clinical Las Vegas (Excel Clinical Research)
state: Nevada
city: Brooklyn
country: United States
facility: SPRI Clinical Trials, LLC
state: New York
city: Poughkeepsie
country: United States
facility: Nuvance Health Medical Practice
state: New York
city: Rochester
country: United States
facility: Rochester Clinical Research
state: New York
city: Asheville
country: United States
facility: Asheville Neurology Specialists
state: North Carolina
city: Greensboro
country: United States
facility: Headache Wellness Center
state: North Carolina
city: Hendersonville
country: United States
facility: Blue Sky MD
state: North Carolina
city: Cincinnati
country: United States
facility: Headache Center of Hope
state: Ohio
city: New Albany
country: United States
facility: The Orthopedic Foundation - Clinic
state: Ohio
city: Wooster
country: United States
facility: Helios Clinical Research
state: Ohio
city: Media
country: United States
facility: Suburban Research Associates
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital - Jefferson Hospital for Neuroscience - Jefferson Neurology Associates - Neurology
state: Pennsylvania
city: North Charleston
country: United States
facility: Coastal Carolina Research Center - North Charleston
state: South Carolina
city: Cordova
country: United States
facility: Neurology Clinic, PC
state: Tennessee
city: Franklin
country: United States
facility: KCA Neurology, PLLC
state: Tennessee
city: Jackson
country: United States
facility: Helios Clinical Research LLC (Helios CR, Inc. Jackson TN)
state: Tennessee
city: Dallas
country: United States
facility: Herzog, Steven MD
state: Texas
city: Dallas
country: United States
facility: Zenos Clinical Research
state: Texas
city: Frisco
country: United States
facility: N TX Inst of Neurology & Headache
state: Texas
city: Frisco
country: United States
facility: Lone Star Neurology
state: Texas
city: Houston
country: United States
facility: Clinical Trial Network
state: Texas
city: Plano
country: United States
facility: Research Your Health
state: Texas
city: Salt Lake City
country: United States
facility: J. Lewis Research Inc.-Foothill
state: Utah
city: West Valley City
country: United States
facility: Metrodora Institute
state: Utah
city: Fairfax
country: United States
facility: Inova Medical Group - Neurology
state: Virginia
city: Columbia
country: United States
facility: MedStar Health - Department of Neurology
state: Washington
city: Kingwood
country: United States
facility: Frontier Clinical Research, LLC
state: West Virginia
city: Greenfield
country: United States
facility: BCN Research, LLC
state: Wisconsin
city: Neenah
country: United States
facility: Neuroscience Group of Northeast Wisconsin-Neenah
state: Wisconsin
city: Montréal
country: Canada
facility: Genge Partners Inc.
city: Red Deer
country: Canada
facility: CARe Clinic-Calgary
city: Sarnia
country: Canada
facility: Bluewater Clinical Research Group Inc.
city: Brno
country: Czechia
facility: Neurologie Brno s.r.o.
city: Brno
country: Czechia
facility: Pratia Brno s.r.o.
city: Chocen
country: Czechia
facility: NEUROHK s.r.o.
city: Jihlava
country: Czechia
facility: Nemocnice Jihlava, p.o.
city: Ostrava
country: Czechia
facility: Fakultni nemocnice Ostrava
city: Praha 8
country: Czechia
facility: Institut neuropsychiatricke pece
city: Praha
country: Czechia
facility: Axon Clinical, s.r.o.
city: Praha
country: Czechia
facility: DADO MEDICAL s.r.o.
city: Praha
country: Czechia
facility: Fakultni Thomayerova nemocnice
city: Amiens
country: France
facility: CHRU d'Amiens
city: Nîmes
country: France
facility: CHU Nimes - Hôpital Caremeau
city: Paris
country: France
facility: Assistance Publique-Hopitaux de Paris (AP-HP) - Unite de Recherche Clinique Saint-Louis Lariboisere-Ferd Widal
city: Batumi
country: Georgia
facility: Ltd "Health"
city: Tbilisi
country: Georgia
facility: "Pineo Medical Ecosystem" LTD
city: Tbilisi
country: Georgia
facility: LTD New Hospitals
city: Tbilisi
country: Georgia
facility: LTD S.Khechinashvili University Hospital
city: Tbilisi
country: Georgia
facility: Multprofil Clinic Consilium Medulla
city: Tbilisi
country: Georgia
facility: ISR-GEO Med Res Clin Healthycore
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin KöR
city: Berlin
country: Germany
facility: Emovis GmbH
city: Greifswald
country: Germany
facility: Universitätsmedizin Greifswald
city: Hessen
country: Germany
facility: Kopfschmerzzentrum Frankfurt am Main
city: München
country: Germany
facility: LMU - Klinikum der Universität München - Campus Grosshadern
city: Bydgoszcz
country: Poland
facility: Centrum Medyczne Neuromed Pawel Lisewski
city: Gdynia
country: Poland
facility: Synexus Polska Sp. z o.o.
city: Katowice
country: Poland
facility: Centrum Medyczne Pratia Katowice
city: Krakow
country: Poland
facility: Krakowska Akademia Neurologii Sp. z o.o.
city: Krakow
country: Poland
facility: Krakowskie Centrum MedyczneSp.z o.o
city: Krakow
country: Poland
facility: Pratia MCM Krakow
city: Lublin
country: Poland
facility: Indywidualna Praktyka Lekarska dr hab. med. Anna Szczepanska-Szerej
city: Oświęcim
country: Poland
facility: Instytut Zdrowia Dr Boczarska-Jedynak Sp. z o.o. S.K.
city: Barcelona
country: Spain
facility: Hospital Universitari Vall D Hebron
city: Madrid
country: Spain
facility: Complejo Hospitalario Ruber Juan Bravo
city: Madrid
country: Spain
facility: Hospital Universitario 12 De Octubre
city: Málaga
country: Spain
facility: Hospital Universitario Regional De Malaga
city: Valencia
country: Spain
facility: Hospital Universitario y Politécnico La Fe
city: Zaragoza
country: Spain
facility: Hospital Clinico Universitario Lozano Blesa
Study officials:
affiliation: Ipsen
name: Ipsen Medical Director
role: STUDY_DIRECTOR
References: