Extension Study of ABP-20001 to Evaluate Safety and Efficacy of Repeat Treatments of ABP-450 for Migraine Prevention

A Randomized, Multicenter, Dose-Blinded, Phase 2 Extension Study of ABP-450 (prabotulinumtoxinA) Purified Neurotoxin Complex for the Prevention of Migraine Headache

This Phase 2 Extension 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 approximately 666 patients across approximately 65 sites in the United States, Canada and Australia from the Phase 2 trial. Study subjects will be divided evenly across a low dose group and a high dose group. All patients will receive four treatment cycles of ABP-450 utilizing the Company's novel injection paradigm.

Study Overview

• Status: Terminated
• Conditions: Migraine
• Intervention / Treatment: Drug: ABP-450

Detailed Description

The Phase 2 Extension 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 approximately 666 patients across approximately 65 sites in the United States, Canada and Australia from Phase 2 trial. Study subjects who had their initial dose of study drug in Phase 2 trial study, irrespective of treatment allocation, will be eligible to enroll in this extension study. Study subjects will be divided evenly across a group receiving a low dose of ABP-450 and a group receiving a high dose of ABP-450. All patients will receive four 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): 466
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Liverpool, New South Wales, Australia, 2170
      • Liverpool Hospital
  • Victoria
    • Camberwell, Victoria, Australia, 3124
      • Emeritus Research
    • Melbourne, Victoria, Australia, 3004
      • Alfred Hospital
• Canada
  • Québec, Canada, G1N 4V3
    • Diex Recherche Québec
  • 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
    • 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
      • Quality 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
    • 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
      • Legacy Clinical Solutions: Tandem Clinical Research, LLC - Clinedge - PPDS
  • 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
  • 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, 89104
      • Wake Research - CRCN, LLC
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Clinical Trials Inc - Clinedge - PPDS
  • New York
    • Amherst, New York, United States, 14226
      • Dent Neurologic Institute
    • Williamsville, New York, United States, 14221
      • Upstate Clinical Research Associates LLC
  • Ohio
    • 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
      • Alina clinical trials
    • Sugar Land, Texas, United States, 77478
      • Houston Neurology Associates
  • 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: 18 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. Patient was enrolled in Study ABP-20001 and successfully completed that study's treatment and procedures.
3. A 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.
4. A WOCBP must have a negative urine pregnancy test at Visit 1.
5. Patient can read, understand, and complete the eDiary.
6. Patient is willing and able to adhere to the study assessments, visit schedules, and prohibitions, as described in this protocol.

Exclusion Criteria:

1. Did not meet eligibility criteria for Study ABP-20001 and was improperly enrolled or randomized in that study.

2. Failure to successfully complete the Study ABP-20001, including the following:

   1. use of prohibited medications
   2. delay of >4 weeks in receiving second Study ABP-20001 investigational study drug injection
   3. completing fewer than 75% of eDiary entries during the 28-week treatment and follow-up periods
   4. 7 or more consecutive missed days of eDiary entries Note: if the investigator determines that any of the above 4 failures occurred due to extenuating circumstances, patients may be allowed to enroll in Study ABP-20002 if the investigator expects the problem will not recur.

   Medical Conditions:

3. History of migraine accompanied by diplopia or decreased level of consciousness, or retinal migraine.
4. Current diagnosis of chronic tension-type headache, new persistent daily headache, trigeminal autonomic cephalgia (eg, cluster headache), or cranial neuropathy.
5. Confounding and clinically significant pain syndromes (eg, fibromyalgia, chronic low back pain, complex regional pain syndromes) as evaluated by the investigator.
6. Diagnosis of myasthenia gravis, Lambert-Eaton syndrome, amyotrophic lateral sclerosis, or any other significant neuromuscular disease that might interfere with the study.
7. Psychiatric conditions that are uncontrolled and/or untreated as evaluated by the investigator.
8. Lifetime history of psychosis, mania, or dementia.
9. History of addiction, including alcohol or drug abuse since initiating ABP-20001 study treatment.
10. Any infection or clinically significant skin problem in any of the injection sites.

11. 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 signing the ICF, 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:

12. 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 time since enrolling in Study ABP-20001.

    Prior/Concomitant Medications and Treatments

13. Injection with anesthesia or steroids in the targeted muscles since initiating ABP-20001 study treatment.
14. Use of opioids or barbiturates >2 days per month since initiating ABP-20001 study treatment.
15. Use of CBD or other types of cannabinoids since initiating ABP-20001 study treatment.
16. Use of botulinum toxin for migraine or any other medical reasons, including cosmetic use, at or above the shoulders outside of Study ABP-20001 since initiating ABP-20001 study treatment and throughout Study ABP-20002.
17. Any CGRP inhibitor treatment (eg, erenumab [Aimovig®], eptinezumab [Vyepti®], fremanezumab [Ajovy®], or galcanezumab [Emgality®], rimegepant sulfate [Nurtec™], ubrogepant [Ubrelvy™] within or outside of a clinical study) since initiating ABP-20001 study treatment.
18. Use of small molecule migraine drugs (eg, beta-blockers, anticonvulsants, antidepressants, calcium channel blockers) since initiating ABP-20001 study treatment.
19. 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) since initiating ABP-20001 study treatment.
20. 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 since initiating ABP-20001 study treatment that, in the opinion of the investigator, would interfere with the investigational study drug.
21. History of inadequate response to 3 classes of medications (which have different mechanisms of action) prescribed for the prevention of migraine, excluding CGRP therapies.
22. History of hypersensitivity to human serum albumin, sucrose, or botulinum toxin type A.
23. Participation in another interventional study since initiating ABP-20001 study treatment. Other Exclusion Criteria:
24. Patients who have been infected with COVID-19 for whom the infection worsened their migraine disorder. Patients for whom infection with COVID-19 did not worsen their migraine disorder may be included in the study.
25. Female patients pregnant or planning on becoming pregnant during the study and/or lactating/breastfeeding.
26. 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

2

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

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 ABP-450 (low dose) or ABP-450 (high dose).	Baseline to Week 52 - End of Study
Change in Monthly Migraine Days	The primary efficacy endpoint will be the change in mean Monthly Migraine Days (MMD) from Baseline to intervals throughout the study.	Baseline to Week 52 - End of Treatment Period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 52 - 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 52 - 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 52 - End of Study
Suicidality by Columbia-Suicide Severity Rating Scale (C-SSRS)	Percentage of Participants with Suicidal Ideation and Behaviors will be assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) with the suicidal ideation on a 5-point scale, ranging from "wish to be dead" to "activesuidical ideatikon with specific plan and intert" and suicidal behaviors of a 4-point scale ranging from "preparatory acts or behavior" to "actual attempt" in lifetime, past 3 months, and since last visit. The higher total scores indicate more suicidal ideation and /or suicidal behavior.	Baseline to Week 52 - 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 52 - 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 throughout the study will be assessed by Treatment Group.	Baseline to Week 52 - 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 with 1-item scale ranging from "much better"k to "much worse" with the higher score indicating worsening of symptoms will be assessed by Treatment Group.	Baseline to Week 52 - 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 with 1-item scale ranging from "normal" to "severely ill" with the higher score indicaating greater severity in illness will be assessed by Treatment Group.	Baseline to Week 52 - 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 52 - 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 with an 8-item scale ranging from "without difficulty" to "extremely difficult". The higher the score represents the highest level of impact.	Baseline to Week 52 - End of Study
Mean change of Migraine-Specific-Quality of Life (MSQ) Domains	The Mean Change in Migraine-Specific-Quality of Life (MSQ), a14-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 52 - End of Study
Percentage of Patients with Reduction in the Physical Impairment Domain 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 with a 5-item scale ranging from "none of the time" to "all of the time" or :without any difficulty" to extremely difficult". The higher the score represents the highest level of impairment.	Baseline to Week 52 - End of Study

Collaborators and Investigators

• Sponsor: AEON Biopharma, Inc.
• Collaborators: PPD Development, LP
• 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): October 19, 2021
• Primary Completion (Actual): July 31, 2024
• Study Completion (Actual): August 30, 2024

Study Registration Dates

• First Submitted: August 17, 2021
• First Submitted That Met QC Criteria: August 17, 2021
• First Posted (Actual): August 23, 2021

Study Record Updates

• Last Update Posted (Actual): September 20, 2024
• Last Update Submitted That Met QC Criteria: September 18, 2024
• Last Verified: September 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-20002

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 a 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