Study to Determine Safety and Efficacy of B244 in Subjects With Episodic Migraine

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03488563

Enrollment

313

Registered

2018-04-05

Start date

2018-03-30

Completion date

2019-07-16

Last updated

2022-10-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Migraine

Keywords

Headache

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.

Interventions

BIOLOGICALB244

B244 Suspension

BIOLOGICALVehicle

Vehicle Suspension

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Masking description

Each participant scheduled to receive investigational product (IP) will receive a randomization number at the time of randomization. The randomization number will be used to identify the study medication kit assigned to the participant and indicate the treatment to be administered to that participant.

Intervention model description

Randomization will be 1:1:1 so that equal number of subjects will be treated in each arm of the study.

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Yes

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.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0	Baseline to Day 112	Safety and tolerability endpoints will consist of all adverse events reporting during the study duration.

Secondary

Measure	Time frame	Description
Mean Change in Monthly Migraine Days.	Baseline to Day 84	Subjects made daily entries to include recordings of migraine frequency, duration, and severity that included information on migraine days (experiencing migraine with or without aura in a given day).
Mean Change in Monthly Migraine Attacks.	Baseline to Day 84	Subjects made daily entries to include recordings of migraine frequency, duration, and severity that included information on migraine attacks (an episode of any qualified migraine headache. To distinguish an attack of long duration from two attacks or to distinguish between attacks and relapses: A migraine attack that is interrupted by sleep, or temporarily remits, and then recurs within 48 hours (i.e., \<48 hours between the start of the migraine attack to the time of the recurrence) will be considered as one attack and not two. -An attack treated successfully with medication but with relapse within 48 hours (i.e., \<48 hours between the start of the migraine attack to the time of recurrence) will be considered as one attack.)
Proportion of Subjects Experiencing a 50%, 75%, and 100% Reduction in Monthly Migraine Days.	Baseline to Day 112	Subjects made daily entries to include recordings of migraine frequency, duration, and severity that included information on migraine days (experiencing migraine with or without aura in a given day).
Mean Change in Monthly Acute Migraine Specific Medication Days.	Baseline to Day 84	Subjects made daily entries to include recordings of migraine frequency, duration, and severity that included use of rescue (acute migraine specific) medications and dosing administration.
Mean Change in Monthly Headache Days.	Baseline to Day 84	Subjects made daily entries to include recordings of migraine frequency, duration, and severity that included information on headache days (a non-migraine headache day)
Mean Change From Baseline to 12 Weeks of Treatment in Disability, as Measured by the Migraine Disability Assessment (MIDAS)	Baseline to Day 84	The Migraine Disability Assessment (MIDAS) questionnaire was administered to study examine the relationship between the impact of migraine and quality of life where subjects scored 5 questions on a scale of 0 to 21+ (0-5=little or no disability, 6-10=mild disability, 11-20=moderate disability, 21+=severe disability). The total score ranges from 0 to 90.
Mean Change From Baseline to 12 Weeks of Treatment in Monthly Headache Impact Test-6 (HIT-6) Questionnaire	Baseline to Day 84	The Headache Impact Test-6 (HIT-6) questionnaire was administered to examine the relationship between impact of migraine and quality of life. The total score ranges from 36 to 78 where a higher score indicates a greater impact on quality of life (Class I: 36-49, Class II: 50-55, Class III: 56-59, Class IV: 60+).
Mean Change From Baseline to 12 Weeks of Treatment in Monthly Migraine Specific Quality of Life Questionnaire (MSQL)	Baseline to Day 84	The Migraine Specific Quality of Life (MSQL) questionnaire was used to examine the impact of migraine on health-related quality of life across three domains: Role Function-Restrictive (7 questions) examines the degree to which performance of daily activities is limited by migraine; Role Function-Preventive (4 questions) examines the degree to which performance of daily activities is prevented by migraine; Emotional Function (3 questions) examines feelings of frustration and helplessness due to migraine. Total score for each domain ranges from 0 to 100, where a higher score indicates greater severity.

Other

Measure	Time frame	Description
Mean Change in Days Where Subject Recorded Migraine Associated Symptoms: Nausea/Vomiting, Photophobia and Sonophobia.	Baseline to Day 112	Subjects made daily entries to include recordings of migraine frequency, duration, and severity that included information on migraine associated symptoms: nausea/vomiting, photophobia and sonophobia.

Countries

United States

Participant flow

Participants by arm

Arm	Count
B244 Dose 1 B244 1X suspension (1x10E9 cells/ml) in 30ml/bottle Subjects will apply 1 pump per nostril twice-a-day B244: B244 Suspension	92
B244 Dose 2 B244 4X suspension (4x10E9 cells/ml) in 30ml/bottle Subjects will apply 1 pump per nostril twice-a-day B244: B244 Suspension	94
Vehicle Vehicle, 30ml/bottle Subjects will apply 1 pump per nostril twice-a-day Vehicle: Vehicle Suspension	88
Total	274

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	1	0	1
Overall Study	Lost to Follow-up	7	6	7
Overall Study	Physician Decision	0	0	1
Overall Study	Protocol Violation	3	2	6
Overall Study	Sponsor's decision	0	0	1
Overall Study	Subject did not meet minimum number of migraines per month	1	0	0
Overall Study	Subject returned for ET visit	0	1	0
Overall Study	Use of prohibited medication	2	0	0
Overall Study	Withdrawal by Subject	8	7	7

Baseline characteristics

Characteristic	B244 Dose 1	Total	Vehicle	B244 Dose 2
Age, Customized <30	16 Participants	44 Participants	16 Participants	12 Participants
Age, Customized ≥30	76 Participants	230 Participants	72 Participants	82 Participants
BMI	30.51 kg/m^2 STANDARD_DEVIATION 8.569	31.00 kg/m^2 STANDARD_DEVIATION 8.675	31.99 kg/m^2 STANDARD_DEVIATION 8.229	30.55 kg/m^2 STANDARD_DEVIATION 9.183
BMI Category 20-<25 kg/m^2	23 Participants	66 Participants	17 Participants	26 Participants
BMI Category <20 kg/m^2	2 Participants	7 Participants	2 Participants	3 Participants
BMI Category 25-<30 kg/m^2	30 Participants	69 Participants	19 Participants	20 Participants
BMI Category ≥30 kg/m^2	37 Participants	132 Participants	50 Participants	45 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants	34 Participants	14 Participants	10 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	82 Participants	238 Participants	72 Participants	84 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	2 Participants	2 Participants	0 Participants
Height	1.66 m STANDARD_DEVIATION 0.084	1.66 m STANDARD_DEVIATION 0.095	1.66 m STANDARD_DEVIATION 0.089	1.66 m STANDARD_DEVIATION 0.111
HIT Score	63.0 units on a scale STANDARD_DEVIATION 5.77	63.7 units on a scale STANDARD_DEVIATION 5.03	63.9 units on a scale STANDARD_DEVIATION 4.86	64.1 units on a scale STANDARD_DEVIATION 4.36
MIDAS Score	30.3 units on a scale STANDARD_DEVIATION 24.23	38.6 units on a scale STANDARD_DEVIATION 43.98	40.1 units on a scale STANDARD_DEVIATION 50.58	45.3 units on a scale STANDARD_DEVIATION 50.94
MSQL Score - Emotional Function	55.9 units on a scale STANDARD_DEVIATION 29.73	52.3 units on a scale STANDARD_DEVIATION 28.25	50.4 units on a scale STANDARD_DEVIATION 27.7	50.5 units on a scale STANDARD_DEVIATION 27.23
MSQL Score - Role Function-Preventive	63.2 units on a scale STANDARD_DEVIATION 21.54	61.8 units on a scale STANDARD_DEVIATION 22.82	61.8 units on a scale STANDARD_DEVIATION 24.13	60.3 units on a scale STANDARD_DEVIATION 22.92
MSQL Score - Role Function-Restrictive	48.1 units on a scale STANDARD_DEVIATION 18.88	45.9 units on a scale STANDARD_DEVIATION 19.9	45.6 units on a scale STANDARD_DEVIATION 20.65	44.1 units on a scale STANDARD_DEVIATION 20.17
Number of Acute Migraine Specific Medication Days	5.5 days STANDARD_DEVIATION 3.6	5.7 days STANDARD_DEVIATION 3.56	6.1 days STANDARD_DEVIATION 3.85	5.5 days STANDARD_DEVIATION 3.22
Number of Headache Days	8.3 days STANDARD_DEVIATION 3.04	8.6 days STANDARD_DEVIATION 3.14	9.3 days STANDARD_DEVIATION 3.44	8.4 days STANDARD_DEVIATION 2.88
Number of Headache Hours	97.0 hours STANDARD_DEVIATION 68.31	100.2 hours STANDARD_DEVIATION 66.65	107.7 hours STANDARD_DEVIATION 66.68	96.4 hours STANDARD_DEVIATION 65.09
Number of Migraine Attacks	4.9 attacks STANDARD_DEVIATION 1.88	5.0 attacks STANDARD_DEVIATION 1.72	5.1 attacks STANDARD_DEVIATION 1.81	5.0 attacks STANDARD_DEVIATION 1.46
Number of Migraine Days	7.4 days STANDARD_DEVIATION 2.86	7.6 days STANDARD_DEVIATION 2.89	8.0 days STANDARD_DEVIATION 3.09	7.4 days STANDARD_DEVIATION 2.71
Number of Moderate and Severe Headache Days	5.7 days STANDARD_DEVIATION 2.88	6.1 days STANDARD_DEVIATION 2.98	6.3 days STANDARD_DEVIATION 3.07	6.2 days STANDARD_DEVIATION 3
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	1 Participants	1 Participants	0 Participants
Race (NIH/OMB) Asian	3 Participants	5 Participants	1 Participants	1 Participants
Race (NIH/OMB) Black or African American	27 Participants	68 Participants	20 Participants	21 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants	4 Participants	0 Participants	3 Participants
Race (NIH/OMB) White	61 Participants	196 Participants	66 Participants	69 Participants
Sex: Female, Male Female	82 Participants	234 Participants	76 Participants	76 Participants
Sex: Female, Male Male	10 Participants	40 Participants	12 Participants	18 Participants
Smoking History Current	2 Participants	25 Participants	14 Participants	9 Participants
Smoking History Former	17 Participants	48 Participants	12 Participants	19 Participants
Smoking History Never	73 Participants	201 Participants	62 Participants	66 Participants
Weight	85.09 kg STANDARD_DEVIATION 25.835	85.85 kg STANDARD_DEVIATION 24.903	89.34 kg STANDARD_DEVIATION 25.94	93.33 kg STANDARD_DEVIATION 22.791

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 105	0 / 104	0 / 104
other Total, other adverse events	45 / 105	42 / 104	49 / 104
serious Total, serious adverse events	3 / 105	0 / 104	0 / 104

Outcome results

Primary

Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0

Safety and tolerability endpoints will consist of all adverse events reporting during the study duration.

Time frame: Baseline to Day 112

Population: Safety population included all subjects who received at least 1 dose of IP. Subjects were analyzed according to the IP received.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
B244 Dose 1	Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0	At Least 1 Treatment-Related Grade 3 or 4 TEAE	1 Participants
B244 Dose 1	Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0	At Least 1 Treatment-Related TEAE	18 Participants
B244 Dose 1	Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0	At Least 1 Treatment-Related Serious TEAE	0 Participants
B244 Dose 2	Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0	At Least 1 Treatment-Related Grade 3 or 4 TEAE	0 Participants
B244 Dose 2	Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0	At Least 1 Treatment-Related TEAE	13 Participants
B244 Dose 2	Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0	At Least 1 Treatment-Related Serious TEAE	0 Participants
Vehicle	Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0	At Least 1 Treatment-Related TEAE	17 Participants
Vehicle	Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0	At Least 1 Treatment-Related Serious TEAE	0 Participants
Vehicle	Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0	At Least 1 Treatment-Related Grade 3 or 4 TEAE	1 Participants

Secondary

Mean Change From Baseline to 12 Weeks of Treatment in Disability, as Measured by the Migraine Disability Assessment (MIDAS)

The Migraine Disability Assessment (MIDAS) questionnaire was administered to study examine the relationship between the impact of migraine and quality of life where subjects scored 5 questions on a scale of 0 to 21+ (0-5=little or no disability, 6-10=mild disability, 11-20=moderate disability, 21+=severe disability). The total score ranges from 0 to 90.