Clinical trial NCT04845178: Investigation of Safety and Efficacy of ABP-450 for Migraine Prevention in Adults
Official title: A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Phase 2 Study of ABP-450 (prabotulinumtoxinA) Purified Neurotoxin Complex for the Prevention of Migraine Headache
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Migraine
Lead sponsor: AEON Biopharma, Inc.
Sponsor class: INDUSTRY
Collaborators: name: PPD Development, LP
First posted: 2021-04-14
Enrollment: 797
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Approximately 765 patients will be randomized in a 1:1:1 ratio and receive 1 of the following 3 treatments: ABP-450 Low Dose, ABP-450 High Dose, or placebo via intramuscular injection into pre-specified areas of the head and neck.
Primary purpose: PREVENTION

Brief summary: This Phase 2 trial will evaluate the efficacy and safety of ABP-450 for migraine prevention in adults who suffer from six or more migraine days per month. The study will enroll 765 patients across approximately 64 sites in the United States, Canada and Australia. Study subjects will be divided evenly across a low dose group, a high dose group and a placebo group. All patients will receive two treatment cycles of ABP-450 or placebo utilizing the Company's novel injection paradigm.

Detailed description: The Phase 2 trial will evaluate the efficacy and safety of ABP-450 for migraine prevention in adults who suffer from six or more migraine days per month. The study will enroll 765 patients across approximately 64 sites in the United States, Canada and Australia. Study subjects will be divided evenly across a low dose of ABP-450 group, a high dose of ABP-450 group, and a placebo group. All patients will receive two treatment cycles utilizing the Company's novel treatment paradigm involving fewer injections than the current botulinum toxin treatment option for chronic migraine.

Eligibility criteria: Inclusion Criteria:

1. Patient can understand the ICF, provides signed ICF and patient privacy information (eg, Authorization for Use and Release of Health and Research Study Information) before initiating any study-specific procedure, and agrees to comply with protocol requirements.
2. Male or female patients 18 years or older of age (no upper age limit) at the time of signing the informed consent.
3. Patient has at least a 1-year history of episodic migraine (with or without aura) or chronic migraine (with or without aura) according to the ICHD-3 (2018) definition and diagnostic criteria.
4. Age of the patient at the time of migraine onset \<50 years.
5. History of, on average ≥6 migraine or probable migraine days per month in the 3 months prior to Screening.
6. Patient is on a stable dose of medications, if any, as recommended by the patient's health care practitioner, used for acute treatment of migraine for at least 3 months prior to Screening. Patient is not taking any migraine prophylactic treatment prohibited per protocol or if on prophylactic treatment has washed out.
7. A Woman of Child Bearing Potential (WOCBP) must be willing and able to use a medically acceptable and effective method of birth control as determined by the investigator, during the entire study.
8. A WOCBP must have a negative pregnancy test at Screening.
9. Patient is able to read, understand, and complete the eDiary.
10. Patient is willing and able to adhere to the study assessments, visit schedules, and prohibitions, as described in this protocol.

Exclusion Criteria:

Medical Conditions

1. History of migraine accompanied by diplopia or decreased level of consciousness, or retinal migraine.
2. Current diagnosis of chronic tension-type headache, new persistent daily headache, trigeminal autonomic cephalgia (eg, cluster headache), or cranial neuropathy.
3. Confounding and clinically significant pain syndromes (eg, fibromyalgia, chronic low back pain, complex regional pain syndromes) as evaluated by the investigator.
4. Diagnosis of myasthenia gravis, Lambert-Eaton syndrome, amyotrophic lateral sclerosis, or any other significant neuromuscular disease that might interfere with the study.
5. Psychiatric conditions that are uncontrolled and/or untreated, including conditions that are not controlled for a minimum of 6 months prior to Screening as evaluated by the investigator. Patients with a lifetime history of psychosis, mania, or dementia are excluded.
6. History of addiction, including alcohol or drugs of abuse, within 6 months prior to Screening.
7. Hepatitis B (HBsAg positive) or hepatitis C (ie, detectable HCV RNA) virus infection.

   Note: Patients with a prior history of treated hepatitis B virus infection who are antigen negative or patients with a prior history of treated HCV infection who are HCV RNA undetectable may be considered after consultation with the study medical monitor.
8. Any infection or clinically significant skin problem in any of the injection sites.
9. Have been injected with anesthesia or steroids in the targeted muscles during the 30 days immediately prior to initiation of the Baseline period.
10. Any medical condition (including but not limited to viral or other active infections) that, in the opinion of the investigator, classifies the patient as unsuitable for participation in the study or patients who do not seem to be in good general health at the time of Screening, and prior to any investigational study drug administration.

    Note: Patients will not routinely be tested for COVID-19 during the study. Patients presenting with fever or who are symptomatic for COVID-19 will be required to be tested and treated through their general practitioner.

    Other Diagnostic Assessments
11. Significant risk of self-harm based on clinical interview and responses on the C-SSRS, or of harm to others in the opinion of the investigator; patients must be excluded if they report suicidal ideation with intent, with or without a plan (ie, Type 4 or 5 on the C-SSRS) in the past 6 months or report suicidal behavior in the past 6 months prior to Screening.
12. Body mass index ≥38 kg/m2 at Screening.

    Prior/Concomitant Medications and Treatments
13. Use of opioids or barbiturates \>2 days per month in the 3 months prior to Screening.
14. Use of CBD or other types of cannabinoids in the 3 months prior to Screening and throughout the study.
15. Any use of botulinum toxin for migraine or any other medical reasons within 4 months prior to Screening and during the Screening and Baseline periods and at or above the shoulders at any time during the study.
16. Any monoclonal antibody CGRP inhibitor treatment (within or outside of a clinical study) within 6 months prior to Screening and throughout the study.
17. Any orally administered non-peptide CGRP antagonists (within or outside of a clinical study) within 4 weeks prior to the Baseline period and throughout the study.
18. Use of devices for the treatment of migraine (ie, non-invasive neuromodulation therapies including but not limited to non-invasive nerve stimulation \[gammaCore\], transcranial magnetic stimulation \[Cefaly\], external trigeminal nerve stimulation, transcutaneous electrical nerve stimulation, and peripheral neuroelectrical stimulation) during Screening and throughout the study.
19. Any other treatments or therapies (eg, acupuncture in head and neck region, cranial traction, nociceptive trigeminal inhibition, occipital nerve block treatments, and dental splints for headache) to the head, neck, or shoulder regions during Screening and throughout the study that, in the opinion of the investigator, would interfere with the investigational study drug.
20. History of inadequate response to 3 classes of medications (which have different mechanisms of action) prescribed for the prevention of migraine, excluding CGRP therapies.
21. History of hypersensitivity to human serum albumin, sucrose, or botulinum toxin type A or a positive test for botulinum toxin type A antibody.

    Prior/Concurrent Clinical Study Experience
22. Participation in another interventional study within 6 months prior to Screening and throughout the study.
23. Female patients planning on becoming pregnant during the course of the study and/or lactating/breastfeeding.
24. Patient has donated or lost a significant volume (\>450 mL) of blood or plasma within 30 days of screening.
25. Patient is an employee or family member of the investigator, study site personnel, PPD, or AEON.

Primary outcomes:
measure: Change in Monthly Migraine Days
timeFrame: Baseline to Weeks 21 to 24 Treatment period.
measure: Incidence of Treatment Emergent Adverse Events
timeFrame: Baseline to Week 28 - End of Study.
Secondary outcomes:
measure: Percentage of Patients with Reduction in Mean Migraine Days (MMD)
timeFrame: Baseline to Week 28 - End of Study.
measure: Mean change in Monthly Migraine Days (MMD)
timeFrame: Baseline to Week 28 - End of Study.
measure: Mean change in Monthly Migraine Days (MMD) requiring medications for acute treatment of migraine or headaches
timeFrame: Baseline to Week 28 - End of Study.
measure: Mean change in Headache Hours
timeFrame: Baseline to Week 28 - End of Study.
measure: Mean Change in Monthly Headache Days
timeFrame: Baseline to Week 28 - End of Study.
measure: Mean change of Migraine-Specific-Quality of Life (MSQ) Domains
timeFrame: Baseline to Week 28 - End of Study.
measure: Percentage of Patients with Reduction in Migraine Physical Function Impact Diary (MPFID)
timeFrame: Baseline to Week 28 - End of Study.
measure: Suicidality by Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline to Week 28 - End of Study.
measure: Development of Anti-Drug Antibodies (ADA) to ABP-450
timeFrame: Baseline to Week 28 - End of Study.
Other outcomes:
measure: Mean Change in Patient Global Impression of Change (PGI-C) Score
timeFrame: Baseline to Week 28 - End of Study.
measure: Mean Change in Patient Global Impression of Severity (PGI-S) Score
timeFrame: Baseline to Week 28 - End of Study.
measure: Mean Change in MIgraine Disability Assessment Score (MIDAS) Total Score
timeFrame: Baseline to Week 28 - End of Study.
measure: Percentage of Patients with Reduction in the Physical Impairment Domaine Score of the Migraine Physical Function Impact Diary (MPFID)
timeFrame: Baseline to Week 28 - End of Study.
Locations:
city: Chandler
country: United States
facility: MDFirst Research
state: Arizona
city: Phoenix
country: United States
facility: Elite Clinical Studies, LLC
state: Arizona
city: Phoenix
country: United States
facility: Arizona Neuroscience Research
state: Arizona
city: Tempe
country: United States
facility: Clinical Research Consortium Arizona
state: Arizona
city: Colton
country: United States
facility: Axiom Research LLC
state: California
city: La Mesa
country: United States
facility: Velocity Research San Diego
state: California
city: Long Beach
country: United States
facility: Collaborative Neuroscience Research
state: California
city: Los Angeles
country: United States
facility: Los Angeles Headache Center
state: California
city: Redlands
country: United States
facility: Anderson Clinical Research
state: California
city: San Diego
country: United States
facility: Artemis Institute For Clinical Research LLC - San Diego - ClinEdge - PPDS
state: California
city: Colorado Springs
country: United States
facility: Delta Waves LLC - Hunt - PPDS
state: Colorado
city: Wheat Ridge
country: United States
facility: Paradigm Clinical Research Centers
state: Colorado
city: Stamford
country: United States
facility: New England Institute for Neurology and Headache
state: Connecticut
city: Hialeah
country: United States
facility: Quality Research of South Florida
state: Florida
city: Lake Mary
country: United States
facility: Sandhill Research, LLC
state: Florida
city: Lake Worth
country: United States
facility: Canvas Clinical Research
state: Florida
city: Miami
country: United States
facility: BioMed Research Institute, INC
state: Florida
city: Miami
country: United States
facility: Medical Research Center, LLC
state: Florida
city: Ocala
country: United States
facility: Renstar Medical Research
state: Florida
city: Palmetto Bay
country: United States
facility: Innovation Medical Research Center
state: Florida
city: Winter Haven
country: United States
facility: Clinical Research of Central Florida - ClinEdge - PPDS
state: Florida
city: Atlanta
country: United States
facility: NeuroTrials Research Inc. - Clinedge - PPDS
state: Georgia
city: Marietta
country: United States
facility: Drug Studies America, Inc
state: Georgia
city: Meridian
country: United States
facility: Velocity Clinical Research - Boise - ERN - PPDS
state: Idaho
city: Chicago
country: United States
facility: Cedar Crosse Research Center
state: Illinois
city: Overland Park
country: United States
facility: Kansas Institute of Research, LLC
state: Kansas
city: Chalmette
country: United States
facility: Crescent City Headache and Neurology Center
state: Louisiana
city: Marrero
country: United States
facility: Tandem Clinical Research
state: Louisiana
city: Boston
country: United States
facility: Boston Clinical Trials Inc
state: Massachusetts
city: Waltham
country: United States
facility: MedVadis Research
state: Massachusetts
city: Farmington Hills
country: United States
facility: Quest Research Institute - Hunt - PPDS
state: Michigan
city: Jackson
country: United States
facility: Henry Ford Allegiance Neurology
state: Michigan
city: Saint Peters
country: United States
facility: StudyMetrix Research, LLC
state: Missouri
city: Springfield
country: United States
facility: Clinvest Research LLC
state: Missouri
city: La Vista
country: United States
facility: Barrett Clinic, P.C. - Clinedge - PPDS
state: Nebraska
city: Omaha
country: United States
facility: Quality Clinical Research
state: Nebraska
city: Las Vegas
country: United States
facility: Wake Research - CRCN, LLC
state: Nevada
city: Berlin
country: United States
facility: Hassman Research Institute - ClinEdge - PPDS
state: New Jersey
city: Albuquerque
country: United States
facility: Albuquerque Clinical Trials Inc
state: New Mexico
city: Amherst
country: United States
facility: Dent Neurologic Institute
state: New York
city: New York
country: United States
facility: New York Neurology Associates
state: New York
city: Williamsville
country: United States
facility: Upstate Clinical Research Associates LLC
state: New York
city: Centerville
country: United States
facility: Dayton Center for Neurological Disorders
state: Ohio
city: Dayton
country: United States
facility: META Medical Research Institute, LLC
state: Ohio
city: Dublin
country: United States
facility: Centricity Research Dublin Multispecialty
state: Ohio
city: New Albany
country: United States
facility: The Orthopedic Foundation
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University, Jefferson Headache Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Preferred Primary Care Physicians
state: Pennsylvania
city: Chattanooga
country: United States
facility: WR-ClinSearch
state: Tennessee
city: Nashville
country: United States
facility: Bryant Research Group
state: Tennessee
city: Dallas
country: United States
facility: DCT - Baxter LLC dba Discovery Clinical Trials
state: Texas
city: Sugar Land
country: United States
facility: Mercury Clinical Research Incorporated
state: Texas
city: Orem
country: United States
facility: Aspen Clinical Research LLC - Clinedge - PPDS
state: Utah
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Ballarat
country: Australia
facility: Grampians Health
state: Victoria
city: Camberwell
country: Australia
facility: Emeritus Research
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Hospital
state: Victoria
city: Red Deer
country: Canada
facility: CARe Clinic
state: Alberta
city: Halifax
country: Canada
facility: True North Clinical Research
state: Nova Scotia
city: Sarnia
country: Canada
facility: Bluewater Clinical Research Group
state: Ontario
city: Québec
country: Canada
facility: Diex Recherche Québec
state: Quebec
Study officials:
affiliation: Albert Einstein College of Medicine
name: Richard B Lipton, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dartmouth-Hitchcock Medical Center
name: Stewart J Tepper, MD
role: PRINCIPAL_INVESTIGATOR
References: