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

• ClinicalTrials.gov Identifier: NCT04845178
• Recruitment Status: Recruiting
• First Posted: April 14, 2021
• Last Update Posted: March 8, 2023
• Sponsor: AEON Biopharma, Inc.
• Collaborator: PPD
• Information provided by (Responsible Party): AEON Biopharma, Inc.

Tracking Information

• First Submitted Date: March 28, 2021
• First Posted Date: April 14, 2021
• Last Update Posted Date: March 8, 2023
• Actual Study Start Date: March 1, 2021
• Estimated Primary Completion Date: November 15, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 22, 2022)

• Incidence of Treatment Emergent Adverse Events [ Time Frame: Baseline to Week 28 - End of Study. ]
  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).
• Change in Monthly Migraine Days [ Time Frame: Baseline to Weeks 21 to 24 Treatment period. ]
  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.

Original Primary Outcome Measures (submitted: April 9, 2021)

• Incidence of Treatment Emergent Adverse Events [ Time Frame: Baseline to Week 28 - End of Study. ]
  The primary safety endpoint will be the incidence of TEAEs throughout the study when dosed with placebo, ABP-450 (150 units), or ABP-450 (195 units).
• Change in Monthly Migraine Days [ Time Frame: Baseline to Weeks 20 to 24 Treatment period. ]
  The primary efficacy endpoint will be the change in mean Monthly Migraine Days (MMD) from the 4-week Baseline period to Weeks 20 to 24 Treatment period.

Current Secondary Outcome Measures (submitted: July 22, 2022)

• Suicidality by Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Baseline to Week 28 - End of Study. ]
  Percentage of patients with Suicidal Ideation and Behaviors will be assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS).
• Development of Anti-Drug Antibodies (ADA) to ABP-450 [ Time Frame: Baseline to Week 28 - End of Study. ]
  Percentage of patients developing Anti-Drug Antibodies to ABP-450 antibodies (binding and if positive, neutralizing) will be assessed.
• Percentage of Patients with Reduction in Mean Migraine Days (MMD) [ Time Frame: Baseline to Week 28 - End of Study. ]
  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.
• Mean change in Monthly Migraine Days (MMD) [ Time Frame: Baseline to Week 28 - End of Study. ]
  Overall mean change from Baseline in the number of MMD will be assessed by Treatment Group.
• Mean change in Monthly Migraine Days (MMD) requiring medications for acute treatment of migraine or headaches [ Time Frame: Baseline to Week 28 - End of Study. ]
  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.
• Mean change in Headache Hours [ Time Frame: Baseline to Week 28 - End of Study. ]
  Overall mean change from Baseline in headache (either moderate or severe) hours will be assessed by Treatment Group.
• Mean Change in Monthly Headache Days [ Time Frame: Baseline to Week 28 - End of Study. ]
  Overall mean change from Baseline in monthly headache days will be assessed by Treatment Group.

Original Secondary Outcome Measures (submitted: April 9, 2021)

• Suicidality by Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Baseline to Week 28 - End of Study. ]
  Percentage of Participants with Suicidal Ideation and Behaviors will be assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS).
• Development of Anti-Drug Antibodies (ADA) to ABP-450 [ Time Frame: Baseline to Week 28 - End of Study. ]
  Percentage of patients developing Anti-Drug Antibodies to ABP-450 antibodies (binding and if positive, neutralizing) will be assessed.
• Percentage of Patients with Reduction in Mean Migraine Days (MMD) [ Time Frame: Baseline to Week 28 - End of Study. ]
  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.
• Mean change in Monthly Migraine Days (MMD) [ Time Frame: Baseline to Week 28 - End of Study. ]
  Overall mean change from Baseline in the number of MMD will be assessed by Treatment Group.
• Mean change in Monthly Migraine Days (MMD) requiring medications for acute treatment of migraine or headaches [ Time Frame: Baseline to Week 28 - End of Study. ]
  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.
• Mean change in Headache Hours [ Time Frame: Baseline to Week 28 - End of Study. ]
  Overall mean change from Baseline in headache (either moderate or severe) hours will be assessed by Treatment Group.
• Mean Change in Monthly Headache Days [ Time Frame: Baseline to Week 28 - End of Study. ]
  Overall mean change from Baseline in monthly headache days will be assessed by Treatment Group.

Current Other Pre-specified Outcome Measures (submitted: July 22, 2022)

• Mean change of Migraine-Specific-Quality of Life (MSQ) Domaines [ Time Frame: Through study completion, an average of 6 months ]
  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.
• Mean Change in Patient Global Impression of Change (PGI-C) Score [ Time Frame: Baseline to Week 28 - End of Study. ]
  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.
• Mean Change in Patient Global Impression of Severity (PGI-S) Score [ Time Frame: Baseline to Week 28 - End of Study. ]
  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.
• Mean Change in MIgraine Disability Assessment Score (MIDAS) Total Score [ Time Frame: Baseline to Week 28 - End of Study. ]
  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).
• Percentage of Patients with Reduction in Migraine Physical Function Impact Diary (MPFID) [ Time Frame: Baseline to Week 28 - End of Study. ]
  Percentage of patients with a reduction from Baseline in the impact on Migraine Physical Function Impact Diary (MPFID) will be assessed by Treatment Group.
• Percentage of Patients with Reduction in the Physical Impairment Domaine Score of the Migraine Physical Function Impact Diary (MPFID) [ Time Frame: Baseline to Week 28 - End of Study. ]
  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.

Original Other Pre-specified Outcome Measures (submitted: April 9, 2021)

• Mean change of Migraine-Specific-Quality of Life (MSQ) Domaines [ Time Frame: Through study completion, an average of 6 months ]
  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.
• Mean Change in Patient Global Impression of Change (PGI-C) Score [ Time Frame: Baseline to Week 28 - End of Study. ]
  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.
• Mean Change in Patient Global Impression of Severity (PGI-S) Score [ Time Frame: Baseline to Week 28 - End of Study. ]
  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.
• Mean Change in MIgraine Disability Assessment Score (MIDAS) Total Score [ Time Frame: Baseline to Week 28 - End of Study. ]
  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).
• Percentage of Patients with Reduction in Migraine Physical Function Impact Diary (MPFID) [ Time Frame: Baseline to Week 28 - End of Study. ]
  Percentage of patients with a reduction from Baseline in the impact on Migraine Physical Function Impact Diary (MPFID) will be assessed by Treatment Group.
• Percentage of Patients with Reduction in the Physical Impairment Domaine Score of the Migraine Physical Function Impact Diary (MPFID) [ Time Frame: Baseline to Week 28 - End of Study. ]
  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.

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
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.

Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:

The investigator, study nurse/other study personnel, and patients will be blinded to the treatment group. An appropriately trained person will reconstitute investigational product, fill masked-labeled syringes and provide them to the investigator, but will not perform any assessments with the patient.

Primary Purpose: Prevention

• Condition: Migraine

Intervention

• Drug: ABP-450
  ABP-450 (prabotulinumtoxinA) contains a 900 kDa botulinum toxin type-A complex produced by the bacterium Clostridium botulinum.
  Other Name: prabotulinumtoxinA
• Drug: Placebo
  0.9% sodium chloride, sterile, unpreserved, USP/PhEur
  Other Names:

  • 0.9% sodium chloride
  • saline

Study Arms

• Experimental: ABP-450 - Low Dose
  ABP-450 Low Dose - intramuscular injections into specified muscles.
  Intervention: Drug: ABP-450
• Experimental: ABP-450 - High Dose
  ABP-450 High Dose - intramuscular injections into specified muscles.
  Intervention: Drug: ABP-450
• Placebo Comparator: Placebo
  Placebo (0.9% saline, sterile, unpreserved, USP/Ph.Eur) intramuscular injections into specified muscles.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 22, 2022): 765
• Original Estimated Enrollment (submitted: April 9, 2021): 690
• Estimated Study Completion Date: February 13, 2024
• Estimated Primary Completion Date: November 15, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Patient can understand the eICF, provides signed eICF 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 (Section 5.8.1).

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.
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.
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 [cephaly], 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.

22. Participation in another interventional study within 6 months prior to Screening and throughout the study.

    Prior/Concomitant Medications and Treatments

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Najeebah Abdul-Musawir, MD, MBA; 949-354-6499; nam@aeonbiopharma.com

• Listed Location Countries: Australia, Canada, United States

Administrative Information

• NCT Number: NCT04845178
• Other Study ID Numbers: ABP-20001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• 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

• Current Responsible Party: AEON Biopharma, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: AEON Biopharma, Inc.
• Original Study Sponsor: Same as current
• Collaborators: PPD

Investigators

• Principal Investigator: Richard B Lipton, MD; Albert Einstein College of Medicine
• Principal Investigator: Stewart J Tepper, MD; Dartmouth-Hitchcock Medical Center

• PRS Account: AEON Biopharma, Inc.
• Verification Date: March 2023