Investigation of Safety and Efficacy of ABP-450 for Migraine Prevention in Adults

A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Phase 2 Study of ABP-450 (prabotulinumtoxinA) Purified Neurotoxin Complex for the Prevention of Migraine Headache

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.

Study Overview

• Status: Completed
• Conditions: Migraine
• Intervention / Treatment: Drug: ABP-450; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 797
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Liverpool, New South Wales, Australia, 2170
      • Liverpool Hospital
  • Victoria
    • Ballarat, Victoria, Australia, 3350
      • Grampians Health
    • Camberwell, Victoria, Australia, 3124
      • Emeritus Research
    • Melbourne, Victoria, Australia, 3004
      • Alfred Hospital
• Canada
  • Québec, Canada, G1N 4V3
    • Diex Recherche Quebec
  • Alberta
    • Red Deer, Alberta, Canada, T4P 1K4
      • CARe Clinic
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3S 1N2
      • True North Clinical Research
  • Ontario
    • Sarnia, Ontario, Canada, N7T 4X3
      • Bluewater Clinical Research Group
• United States
  • Arizona
    • Chandler, Arizona, United States, 85226
      • MDFirst Research
    • Phoenix, Arizona, United States, 85018
      • Elite Clinical Studies, LLC
    • Phoenix, Arizona, United States, 85032
      • Arizona Neuroscience Research
    • Tempe, Arizona, United States, 85281
      • Clinical Research Consortium Arizona
  • California
    • Colton, California, United States, 92324
      • Axiom Research LLC
    • La Mesa, California, United States, 91942
      • Velocity Research San Diego
    • Long Beach, California, United States, 90806
      • Collaborative Neuroscience Research
    • Los Angeles, California, United States, 90067
      • Los Angeles Headache Center
    • Redlands, California, United States, 92374
      • Anderson Clinical Research
    • San Diego, California, United States, 92103
      • Artemis Institute For Clinical Research LLC - San Diego - ClinEdge - PPDS
  • Colorado
    • Colorado Springs, Colorado, United States, 80918
      • Delta Waves LLC - Hunt - PPDS
    • Wheat Ridge, Colorado, United States, 80033
      • Paradigm Clinical Research Centers
  • Connecticut
    • Stamford, Connecticut, United States, 06905
      • New England Institute for Neurology and Headache
  • Florida
    • Hialeah, Florida, United States, 33016
      • Community Research of South Florida
    • Lake Mary, Florida, United States, 32746
      • Sandhill Research, LLC
    • Lake Worth, Florida, United States, 33467
      • Canvas Clinical Research
    • Miami, Florida, United States, 33126
      • Biomed Research Institute, Inc
    • Miami, Florida, United States, 33144
      • Medical Research Center, LLC
    • Ocala, Florida, United States, 34470
      • Renstar Medical Research
    • Palmetto Bay, Florida, United States, 33157
      • Innovation Medical Research Center
    • Winter Haven, Florida, United States, 33810
      • Clinical Research of Central Florida - ClinEdge - PPDS
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • NeuroTrials Research Inc. - Clinedge - PPDS
    • Marietta, Georgia, United States, 30060
      • Drug Studies America, Inc
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Velocity Clinical Research - Boise - ERN - PPDS
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Cedar Crosse Research Center
  • Kansas
    • Overland Park, Kansas, United States, 66211
      • Kansas Institute of Research, LLC
  • Louisiana
    • Chalmette, Louisiana, United States, 70043
      • Crescent City Headache and Neurology Center
    • Marrero, Louisiana, United States, 70072
      • Tandem Clinical Research
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Boston Clinical Trials Inc
    • Waltham, Massachusetts, United States, 02451
      • MedVadis Research
  • Michigan
    • Farmington Hills, Michigan, United States, 40825
      • Quest Research Institute - Hunt - PPDS
    • Jackson, Michigan, United States, 49201
      • Henry Ford Allegiance Neurology
  • Missouri
    • Saint Peters, Missouri, United States, 63303
      • StudyMetrix Research, LLC
    • Springfield, Missouri, United States, 65810
      • Clinvest Research LLC
  • Nebraska
    • La Vista, Nebraska, United States, 68128
      • Barrett Clinic, P.C. - Clinedge - PPDS
    • Omaha, Nebraska, United States, 68114
      • Quality Clinical Research
  • Nevada
    • Las Vegas, Nevada, United States, 89118
      • Wake Research - CRCN, LLC
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Hassman Research Institute - ClinEdge - PPDS
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Clinical Trials Inc
  • New York
    • Amherst, New York, United States, 14226
      • Dent Neurologic Institute
    • New York, New York, United States, 10003
      • New York Neurology Associates
    • Williamsville, New York, United States, 14221
      • Upstate Clinical Research Associates LLC
  • Ohio
    • Centerville, Ohio, United States, 45459
      • Dayton Center for Neurological Disorders
    • Dayton, Ohio, United States, 45432
      • META Medical Research Institute, LLC
    • Dublin, Ohio, United States, 43016
      • Centricity Research Dublin Multispecialty
    • New Albany, Ohio, United States, 43054
      • The Orthopedic Foundation
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University, Jefferson Headache Center
    • Pittsburgh, Pennsylvania, United States, 15236
      • Preferred Primary Care Physicians
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • WR-ClinSearch
    • Nashville, Tennessee, United States, 37203
      • Bryant Research Group
  • Texas
    • Dallas, Texas, United States, 75225
      • DCT - Baxter LLC dba Discovery Clinical Trials
    • Sugar Land, Texas, United States, 77478
      • Mercury Clinical Research Incorporated
  • Utah
    • Orem, Utah, United States, 84058
      • Aspen Clinical Research LLC - Clinedge - PPDS
  • Washington
    • Bellevue, Washington, United States, 98004
      • Northwest Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ABP-450 - Low Dose; ABP-450 Low Dose - intramuscular injections into specified muscles.	Drug: ABP-450; ABP-450 (prabotulinumtoxinA) contains a 900 kDa botulinum toxin type-A complex produced by the bacterium Clostridium botulinum.; Other Names: prabotulinumtoxinA
Experimental: ABP-450 - High Dose; ABP-450 High Dose - intramuscular injections into specified muscles.	Drug: ABP-450; ABP-450 (prabotulinumtoxinA) contains a 900 kDa botulinum toxin type-A complex produced by the bacterium Clostridium botulinum.; Other Names: prabotulinumtoxinA
Placebo Comparator: Placebo; Placebo (0.9% saline, sterile, unpreserved, USP/Ph.Eur) intramuscular injections into specified muscles.	Drug: Placebo; 0.9% sodium chloride, sterile, unpreserved, USP/PhEur; Other Names: saline; 0.9% sodium chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment Emergent Adverse Events	The primary safety endpoint will be the incidence of TEAEs throughout the study when dosed with placebo, ABP-450 (low dose), or ABP-450 (high dose).	Baseline to Week 28 - End of Study.
Change in Monthly Migraine Days	The primary efficacy endpoint will be the change in mean Monthly Migraine Days (MMD) from the 4-week Baseline period to Weeks 21 to 24 Treatment period.	Baseline to Weeks 21 to 24 Treatment period.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Suicidality by Columbia-Suicide Severity Rating Scale (C-SSRS)	Percentage of patients with Suicidal Ideation and Behaviors will be assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS).	Baseline to Week 28 - End of Study.
Development of Anti-Drug Antibodies (ADA) to ABP-450	Percentage of patients developing Anti-Drug Antibodies to ABP-450 antibodies (binding and if positive, neutralizing) will be assessed.	Baseline to Week 28 - End of Study.
Percentage of Patients with Reduction in Mean Migraine Days (MMD)	Percentage of patients with a reduction from Baseline of ≥ 50 percent, ≥ 75 percent and 100% percent in average number of MMD will be assessed by Treatment Group.	Baseline to Week 28 - End of Study.
Mean change in Monthly Migraine Days (MMD)	Overall mean change from Baseline in the number of MMD will be assessed by Treatment Group.	Baseline to Week 28 - End of Study.
Mean change in Monthly Migraine Days (MMD) requiring medications for acute treatment of migraine or headaches	Overall mean change from Baseline in number of MMD requiring migraine specific medication and non-specific medications for the acute treatment of migraine or headache will be assessed by Treatment Group.	Baseline to Week 28 - End of Study.
Mean change in Headache Hours	Overall mean change from Baseline in headache (either moderate or severe) hours will be assessed by Treatment Group.	Baseline to Week 28 - End of Study.
Mean Change in Monthly Headache Days	Overall mean change from Baseline in monthly headache days will be assessed by Treatment Group.	Baseline to Week 28 - End of Study.
Percentage of Patients with Reduction in Migraine Physical Function Impact Diary (MPFID)	Percentage of patients with a reduction from Baseline in the impact on Migraine Physical Function Impact Diary (MPFID) will be assessed by Treatment Group.	Baseline to Week 28 - End of Study.
Mean change of Migraine-Specific-Quality of Life (MSQ) Domains	The Mean Change in Migraine-Specific-Quality of Life (MSQ), a 14-item assessment, with each item rated on a 6-point scale (ranging from "none of the time" to "all of the time") with higher scores indicating better quality of life will be assessed by Treatment Group.	Baseline to Week 28 - End of Study.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change in Patient Global Impression of Change (PGI-C) Score	The Mean change in the subject's assessment of the change in clinical status since the start of treatment measured by the Patients' Global Impression of Change (PGI-C) Scale will be assessed by Treatment Group.	Baseline to Week 28 - End of Study.
Mean Change in Patient Global Impression of Severity (PGI-S) Score	The Mean change in the subject's assessment of the severity of their condition since the start of treatment measured by the Patients' Global Impression of Severity (PGI-S) Scale will be assessed by Treatment Group.	Baseline to Week 28 - End of Study.
Mean Change in MIgraine Disability Assessment Score (MIDAS) Total Score	The Mean Change in the Migraine Disability Assessment Scale (MIDAS) between Baseline and End of Treatment assessed by Treatment Group. MIDAS is a 5-item self-administered questionnaire. The 5 items sum to a total MIDAS score of 0 to 155. A higher score indicates greater headache-related disability (worse score).	Baseline to Week 28 - End of Study.
Percentage of Patients with Reduction in the Physical Impairment Domaine Score of the Migraine Physical Function Impact Diary (MPFID)	Percentage of patients with a reduction from Baseline on Physical Impairment Domain Score measured by Migraine Physical Function Impact Diary (MPFID) assessed by Treatment Group.	Baseline to Week 28 - End of Study.

Collaborators and Investigators

• Sponsor: AEON Biopharma, Inc.
• Collaborators: PPD
• Investigators: Principal Investigator: Richard B Lipton, MD, Albert Einstein College of Medicine; Principal Investigator: Stewart J Tepper, MD, Dartmouth-Hitchcock Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Actual): June 19, 2024
• Study Completion (Actual): August 6, 2024

Study Registration Dates

• First Submitted: March 28, 2021
• First Submitted That Met QC Criteria: April 9, 2021
• First Posted (Actual): April 14, 2021

Study Record Updates

• Last Update Posted (Actual): September 4, 2024
• Last Update Submitted That Met QC Criteria: August 30, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders
• Other Study ID Numbers: ABP-20001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual Participant Data collected during the trial, after deidentification may be shared following review of the clinical study report by the FDA review division and if a decision is made to publish the results in an publication outside posting the results in clinicaltrials.gov

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No