Clinical trial NCT03488563: Study to Determine Safety and Efficacy of B244 in Subjects With Episodic Migraine
Official title: A Prospective, Randomized, Vehicle-Controlled, Double-Blind, Phase 2 Study to Assess the Safety, Tolerability, and Efficacy of B244 Delivered as an Intranasal Spray for Preventive Treatment in Subjects With Episodic Migraine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Migraine
Keywords: Headache
Lead sponsor: AOBiome LLC
Sponsor class: INDUSTRY
Collaborators: name: Veristat, Inc.
First posted: 2018-04-05
Enrollment: 313
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomization will be 1:1:1 so that equal number of subjects will be treated in each arm of the study.
Primary purpose: PREVENTION

Brief summary: This is a prospective, randomized, vehicle-controlled, double-blind, multi-center study assessing the safety, tolerability, and efficacy of B244 delivered as an intranasal spray for preventive treatment in subjects with episodic migraine.

Detailed description: This is a Prospective, Randomized, Vehicle-controlled, Double-blind, Multi-center, 3-arm study assessing the safety, tolerability, and efficacy of B244 delivered as an intranasal spray for preventive treatment in subjects with episodic migraine.

At Screening and Baseline, all subjects must experiences 4-14 migraine days per month and 3-14 migraine attacks per month and no more than 14 headache days per month in the 3 months prior to screening.

The total duration of the study will be approximately 16 weeks. Participants will report for a Screening visit and if all inclusion criteria are met, subjects will go through a one month baseline period prior to randomization. Subjects will come in for visits at Day 28 (Week 4), Day 56 (Week8), Day 84 (Week12), and Day 112 (Week 16).

Efficacy will be assessed by change in migraine attacks, days, and hours. Blood and urine samples will be collected for standard safety laboratory testing and the effect of the drug on inflammatory biomarkers. Safety will be monitored throughout the study.

Investigators plan to enroll 303 total subjects. Subjects will be randomized 1:1:1 so that an equal number of subjects will be treated in each arm of the study.

Eligibility criteria: Inclusion Criteria:

* Males and Females, 18 to 65 years of age.
* In good general health as determined by a thorough medical history and physical examination, and vital signs.
* At least a 1-year history of migraine with or without aura that began before the age of 50 years old and consistent with a diagnosis of migraine with or without aura according to the International Classification of Headache Disorders, 3rd edition, beta version.
* Experiences 4-14 migraine days per month and 3-14 migraine attacks per month and no more than 14 headache days per month (including migraine and non-migraine headache days) in the 3 months prior to screening.
* Experiences 4-14 migraine headache days per month during the baseline period.
* Ability and willingness to abstain from taking medications not allowed by the protocol or administering any foreign substance intranasally.
* Ability and willingness to complete a migraine-history diary from screening to treatment with study drug and a migraine-treatment diary from prevention treatment through the remainder of the follow-up period.

Exclusion Criteria:

* Headache on greater than 14 days/month in any of the three months (90 days) preceding entry into the study.
* Use of acute migraine-specific medications (e.g., ergotamine, triptan) on more than 10 days per month in the previous 3 months and during study.
* Use of intranasal migraine medications during study.
* Use of any intranasally administered over-the-counter product or nasal irrigation (e.g., neti pot) during study.
* Opioids/barbiturates used on more than 4 days per month in the previous 3 months and throughout the duration of the study.
* Use of analgesics (including acetaminophen, nonsteroidal anti-inflammatory drugs \[NSAIDs\], acetylsalicylic acid, or combination analgesics) for migraine and non-migraine headaches on more than 14 days per month in the - Use of migraine prevention medication within two months prior to study and throughout the duration of the study.
* Botulinum toxin injection within 3 months prior to screening or during study.
* Anti-CGRP monoclonal antibody (e.g., erenumab, fremanezumab, galcanezumab, and eptinezumab) injection or infusion within 4 months prior to screening or during study.
* Small molecule anti-CGRP medications in the 30 days prior to the screening visit.
* Use of systemic antibiotics during study.
* Pregnancy or breast-feeding.
* Female of childbearing potential not using adequate contraceptive measures.
* Inability to give informed consent.
* History of neurological, psychiatric, or any other medical condition that in the opinion of the investigator may compromise the subject's ability to safely participate in the study.
* Subjects with any significant clinical abnormalities which may interfere with study participation.
* Prior use of AO+ Mist.
* Subjects with immunodeficiencies, nasal lesions, nasal polyps, or sinus infections.
* Subjects who have participated in an investigational drug trial in the 30 days prior to the screening visit.
* Inability to maintain at least 80% diary compliance during the study from baseline to follow-up.

Primary outcomes:
measure: Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
timeFrame: Baseline to Day 112
Secondary outcomes:
measure: Mean Change in Monthly Migraine Days.
timeFrame: Baseline to Day 84
measure: Mean Change in Monthly Migraine Attacks.
timeFrame: Baseline to Day 84
measure: Proportion of Subjects Experiencing a 50%, 75%, and 100% Reduction in Monthly Migraine Days.
timeFrame: Baseline to Day 112
measure: Mean Change in Monthly Acute Migraine Specific Medication Days.
timeFrame: Baseline to Day 84
measure: Mean Change in Monthly Headache Days.
timeFrame: Baseline to Day 84
measure: Mean Change From Baseline to 12 Weeks of Treatment in Disability, as Measured by the Migraine Disability Assessment (MIDAS)
timeFrame: Baseline to Day 84
measure: Mean Change From Baseline to 12 Weeks of Treatment in Monthly Headache Impact Test-6 (HIT-6) Questionnaire
timeFrame: Baseline to Day 84
measure: Mean Change From Baseline to 12 Weeks of Treatment in Monthly Migraine Specific Quality of Life Questionnaire (MSQL)
timeFrame: Baseline to Day 84
Other outcomes:
measure: Mean Change in Days Where Subject Recorded Migraine Associated Symptoms: Nausea/Vomiting, Photophobia and Sonophobia.
timeFrame: Baseline to Day 112
Locations:
city: Little Rock
country: United States
facility: Baptist Health Center for Clinical Research
state: Arkansas
city: Long Beach
country: United States
facility: Collaborative Neuroscience Network, LLC
state: California
city: Riverside
country: United States
facility: CI Trials
state: California
city: Santa Monica
country: United States
facility: Neurological Research Institute
state: California
city: Stamford
country: United States
facility: New England Institute for Neurology and Headache (NEINH)/Medical Practice
state: Connecticut
city: Jacksonville
country: United States
facility: Clinical Neuroscience Solution, Inc
state: Florida
city: Lauderdale Lakes
country: United States
facility: Precision Clinical Research
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solution, Inc
state: Florida
city: West Palm Beach
country: United States
facility: Palm Beach Research
state: Florida
city: Decatur
country: United States
facility: Neurostudies Clinical Research
state: Georgia
city: New Bedford
country: United States
facility: BTC of New Bedford
state: Massachusetts
city: Watertown
country: United States
facility: MedVadis Research
state: Massachusetts
city: Las Vegas
country: United States
facility: Altea Research Institute
state: Nevada
city: Rochester
country: United States
facility: Rochester Clinical Research INC
state: New York
city: Wilmington
country: United States
facility: PMG Research of Wilmington
state: North Carolina
city: Cincinnati
country: United States
facility: CTI Clinical Research Center
state: Ohio
city: North Charleston
country: United States
facility: Coastal Carolina Research Center
state: South Carolina
city: Memphis
country: United States
facility: Clinical Neuroscience Solution, Inc
state: Tennessee
city: Austin
country: United States
facility: FutureSearch Trials of Neurology and Sleep Lab, L.P.
state: Texas
city: Dallas
country: United States
facility: FutureSearch Trials of Dallas, L.P.
state: Texas
city: Houston
country: United States
facility: Texas Center for Drug Development
state: Texas
city: Charlottesville
country: United States
facility: Charlottesville Medical Research
state: Virginia
Study officials:
affiliation: Chief Medical Officer
name: Judith Ng-Cashin, MD
role: STUDY_DIRECTOR
References: