Trial Outcomes & Findings for Efficacy of AJOVY (Fremanezumab-vfrm) on Interictal Migraine Related Burden (NCT NCT04461795)

NCT ID: NCT04461795

Last Updated: 2022-04-13

Results Overview

The Migraine Interictal Burden Scale (MIBS-4) is a 4-item, self-administered questionnaire which measures interictal migraine-related burden in 4 domains: impairment in work or school, impairment in family and social life, difficulty making plans or commitments, and emotional/affective and cognitive distress. Possible scores range from 0 (No interictal burden) to 12 (Severe interictal burden). Change = (Applicable Treatment Month Score - Baseline Score)

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 40 participants
• Primary outcome timeframe: Baseline to Weeks 4, 8, and 12
• Results posted on: 2022-04-13

Participant Flow

Participant milestones

Measure	AJOVY (Fremanezumab-vfrm) Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks. Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution \[AJOVY\]: 225 MG/1.5 ML Subcutaneous Solution
Overall Study STARTED	40
Overall Study COMPLETED	35
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Measure	AJOVY (Fremanezumab-vfrm) Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks. Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution \[AJOVY\]: 225 MG/1.5 ML Subcutaneous Solution
Overall Study Lost to Follow-up	2
Overall Study Withdrawal by Subject	2
Overall Study Protocol Specified Withdrawal Criterion Met	1

Baseline Characteristics

Efficacy of AJOVY (Fremanezumab-vfrm) on Interictal Migraine Related Burden

Baseline characteristics by cohort

Measure	AJOVY (Fremanezumab-vfrm) n=40 Participants Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks. Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution \[AJOVY\]: 225 MG/1.5 ML Subcutaneous Solution
Age, Continuous	44.38 years STANDARD_DEVIATION 11.20 • n=5 Participants
Sex: Female, Male Female	36 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	40 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants
Race (NIH/OMB) White	35 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	40 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Weeks 4, 8, and 12

Population: All participants enrolled and with at least one administration of investigational product (IP), will be included in this study population. The Full Analysis Population will be used to analyze the efficacy and safety endpoints.

The Migraine Interictal Burden Scale (MIBS-4) is a 4-item, self-administered questionnaire which measures interictal migraine-related burden in 4 domains: impairment in work or school, impairment in family and social life, difficulty making plans or commitments, and emotional/affective and cognitive distress. Possible scores range from 0 (No interictal burden) to 12 (Severe interictal burden). Change = (Applicable Treatment Month Score - Baseline Score)

Outcome measures

Measure	AJOVY (Fremanezumab-vfrm) - Responder n=21 Participants Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks. Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution \[AJOVY\]: 225 MG/1.5 ML Subcutaneous Solution Participants meeting the 50% response criteria (responders) were identified using participants' self-reported data. Responders for the purpose of this study are defined as any participant with ≥ 50% reduction in the number of migraines from baseline to at least 2 out of the 3 treatment periods.	AJOVY (Fremanezumab-vfrm) - Non-Responder n=19 Participants Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks. Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution \[AJOVY\]: 225 MG/1.5 ML Subcutaneous Solution Participants not meeting the 50% response criteria (non-responders) were identified using participants' self-reported data. Non-responders for the purpose of this study are defined as any participant with \< 50% reduction in the number of migraines from baseline to at least 2 out of the 3 treatment periods.
Change in Migraine Interictal Burden Scale (MIBS-4) Scores From Baseline to Weeks 4, 8, and 12. Week 4	-1.05 score on a scale Standard Deviation 2.04	-0.37 score on a scale Standard Deviation 1.57
Change in Migraine Interictal Burden Scale (MIBS-4) Scores From Baseline to Weeks 4, 8, and 12. Week 8	-1.71 score on a scale Standard Deviation 2.59	-0.63 score on a scale Standard Deviation 2.57
Change in Migraine Interictal Burden Scale (MIBS-4) Scores From Baseline to Weeks 4, 8, and 12. Week 12	-1.71 score on a scale Standard Deviation 2.10	-1.16 score on a scale Standard Deviation 2.81

SECONDARY outcome

Timeframe: Baseline to Weeks 4, 8, and 12

Population: All participants enrolled and with at least one administration of investigational product (IP), will be included in this study population. The Full Analysis Population will be used to analyze the efficacy and safety endpoints.

Comparison of the mean change from baseline in the frequency of migraine headache days per 28-day period ending with the cessation of treatment month 3. A migraine headache day will be defined as a calendar day (00:00 to 23:59) with 4 or more hours of migraine headache, fulfilling International Classification of Headache Disorders-3 criteria, and/or any headache of any duration with the use of migraine-specific acute medications(s) (i.e. ergot alkaloids, ergot combinations, opioids, triptans, combination analgesics [simple analgesics combined with opioids or barbiturate with or without caffeine]). Change = (Applicable Treatment Month Score - Baseline Score)

Outcome measures

Measure	AJOVY (Fremanezumab-vfrm) - Responder n=21 Participants Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks. Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution \[AJOVY\]: 225 MG/1.5 ML Subcutaneous Solution Participants meeting the 50% response criteria (responders) were identified using participants' self-reported data. Responders for the purpose of this study are defined as any participant with ≥ 50% reduction in the number of migraines from baseline to at least 2 out of the 3 treatment periods.	AJOVY (Fremanezumab-vfrm) - Non-Responder n=19 Participants Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks. Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution \[AJOVY\]: 225 MG/1.5 ML Subcutaneous Solution Participants not meeting the 50% response criteria (non-responders) were identified using participants' self-reported data. Non-responders for the purpose of this study are defined as any participant with \< 50% reduction in the number of migraines from baseline to at least 2 out of the 3 treatment periods.
Change in Number of Monthly Migraine Days From Baseline to Weeks 4, 8, and 12. Week 4	-6.05 migraine days Standard Deviation 3.41	-0.9 migraine days Standard Deviation 3.8
Change in Number of Monthly Migraine Days From Baseline to Weeks 4, 8, and 12. Week 8	-6.71 migraine days Standard Deviation 3.09	-2.42 migraine days Standard Deviation 3.34
Change in Number of Monthly Migraine Days From Baseline to Weeks 4, 8, and 12. Week 12	-7.00 migraine days Standard Deviation 3.30	-3.53 migraine days Standard Deviation 3.89

SECONDARY outcome

Timeframe: Baseline to Weeks 4, 8, and 12

Population: All participants enrolled and with at least one administration of investigational product (IP), will be included in this study population. The Full Analysis Population will be used to analyze the efficacy and safety endpoints.

The Neuro-QoL Sleep Disturbance Short Form (SDSF) is an 8-item, self-administered questionnaire which measures quality of sleep including difficulties and perception of sleep satisfaction. Possible scores range from 8 to 40, with higher scores indicating worse sleep habits. Change = (Applicable Treatment Month Score - Baseline Score)

Outcome measures

Measure	AJOVY (Fremanezumab-vfrm) - Responder n=21 Participants Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks. Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution \[AJOVY\]: 225 MG/1.5 ML Subcutaneous Solution Participants meeting the 50% response criteria (responders) were identified using participants' self-reported data. Responders for the purpose of this study are defined as any participant with ≥ 50% reduction in the number of migraines from baseline to at least 2 out of the 3 treatment periods.	AJOVY (Fremanezumab-vfrm) - Non-Responder n=19 Participants Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks. Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution \[AJOVY\]: 225 MG/1.5 ML Subcutaneous Solution Participants not meeting the 50% response criteria (non-responders) were identified using participants' self-reported data. Non-responders for the purpose of this study are defined as any participant with \< 50% reduction in the number of migraines from baseline to at least 2 out of the 3 treatment periods.
Change in Neuro-QoL Sleep Disturbance Short Form (SDSF) Scores From Baseline to Weeks 4, 8, and 12. Week 12	-4.66 score on a scale Standard Deviation 5.75	-5.23 score on a scale Standard Deviation 6.06
Change in Neuro-QoL Sleep Disturbance Short Form (SDSF) Scores From Baseline to Weeks 4, 8, and 12. Week 4	-2.85 score on a scale Standard Deviation 5.20	-4.33 score on a scale Standard Deviation 6.86
Change in Neuro-QoL Sleep Disturbance Short Form (SDSF) Scores From Baseline to Weeks 4, 8, and 12. Week 8	-4.30 score on a scale Standard Deviation 5.49	-3.5 score on a scale Standard Deviation 6.87

SECONDARY outcome

Timeframe: Baseline to Weeks 4, 8, and 12

Population: All participants enrolled and with at least one administration of investigational product (IP), will be included in this study population. The Full Analysis Population will be used to analyze the efficacy and safety endpoints.

The General Self-Efficacy - Short Form (GSE-SF) is a 4 item, self-administered questionnaire where the participant is asked to rate their confidence in managing situations, problems, and events. Scores range from 4-20. Higher scores indicate the participant has more self-efficacy managing difficult situations. Change = (Applicable Treatment Month Score - Baseline Score)

Outcome measures

Measure	AJOVY (Fremanezumab-vfrm) - Responder n=21 Participants Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks. Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution \[AJOVY\]: 225 MG/1.5 ML Subcutaneous Solution Participants meeting the 50% response criteria (responders) were identified using participants' self-reported data. Responders for the purpose of this study are defined as any participant with ≥ 50% reduction in the number of migraines from baseline to at least 2 out of the 3 treatment periods.	AJOVY (Fremanezumab-vfrm) - Non-Responder n=19 Participants Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks. Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution \[AJOVY\]: 225 MG/1.5 ML Subcutaneous Solution Participants not meeting the 50% response criteria (non-responders) were identified using participants' self-reported data. Non-responders for the purpose of this study are defined as any participant with \< 50% reduction in the number of migraines from baseline to at least 2 out of the 3 treatment periods.
Change in General Self-Efficacy - Short Form (GSE-SF) Scores From Baseline to Weeks 4, 8, and 12. Week 4	-0.12 score on a scale Standard Deviation 7.02	2.04 score on a scale Standard Deviation 7.96
Change in General Self-Efficacy - Short Form (GSE-SF) Scores From Baseline to Weeks 4, 8, and 12. Week 8	0.46 score on a scale Standard Deviation 9.13	1.55 score on a scale Standard Deviation 9.00
Change in General Self-Efficacy - Short Form (GSE-SF) Scores From Baseline to Weeks 4, 8, and 12. Week 12	2.04 score on a scale Standard Deviation 7.44	0.98 score on a scale Standard Deviation 9.19

SECONDARY outcome

Timeframe: Baseline to Weeks 4, 8, and 12

Population: All participants enrolled and with at least one administration of investigational product (IP), will be included in this study population. The Full Analysis Population will be used to analyze the efficacy and safety endpoints.

The Patient-Reported Outcomes Measurement Information System 29 (PROMIS 29) has 7 domains each with 4 questions, and then one global Pain Intensity item. The domains include: Physical Function, Anxiety, Depression, Fatigue, Sleep Disturbance, Ability to Participate in Social Roles and Activities, and Pain Interference. The global item domain is Pain Intensity. Each PROMIS domain can range from a score of 4-20, higher scores equals more of the concept being measured (e.g., more Fatigue, more Physical Function).

The outcome measure for this endpoint is the change in the global item (Pain Intensity) from baseline. The Global Pain Intensity item can range from 0-10, with higher scores indicating more severe pain intensity. Change = (Applicable Treatment Month Score - Baseline Score)

Outcome measures

Measure	AJOVY (Fremanezumab-vfrm) - Responder n=21 Participants Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks. Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution \[AJOVY\]: 225 MG/1.5 ML Subcutaneous Solution Participants meeting the 50% response criteria (responders) were identified using participants' self-reported data. Responders for the purpose of this study are defined as any participant with ≥ 50% reduction in the number of migraines from baseline to at least 2 out of the 3 treatment periods.	AJOVY (Fremanezumab-vfrm) - Non-Responder n=19 Participants Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks. Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution \[AJOVY\]: 225 MG/1.5 ML Subcutaneous Solution Participants not meeting the 50% response criteria (non-responders) were identified using participants' self-reported data. Non-responders for the purpose of this study are defined as any participant with \< 50% reduction in the number of migraines from baseline to at least 2 out of the 3 treatment periods.
Change in Patient-Reported Outcomes Measurement Information System 29 (PROMIS 29) Global Pain Intensity Scores From Baseline to Weeks 4, 8, and 12. Week 4	-2.24 score on a scale Standard Deviation 2.63	-0.95 score on a scale Standard Deviation 1.75
Change in Patient-Reported Outcomes Measurement Information System 29 (PROMIS 29) Global Pain Intensity Scores From Baseline to Weeks 4, 8, and 12. Week 8	-2.29 score on a scale Standard Deviation 2.55	-1.16 score on a scale Standard Deviation 1.77
Change in Patient-Reported Outcomes Measurement Information System 29 (PROMIS 29) Global Pain Intensity Scores From Baseline to Weeks 4, 8, and 12. Week 12	-2.19 score on a scale Standard Deviation 2.73	-1.74 score on a scale Standard Deviation 2.00

SECONDARY outcome

Timeframe: Baseline to Weeks 4, 8, and 12

Population: All participants enrolled and with at least one administration of investigational product (IP), will be included in this study population. The Full Analysis Population will be used to analyze the efficacy and safety endpoints.

The Work Productivity and Activity Impairment - Migraine (WPAI-M) is a 6-item self-administered questionnaire that measures work productivity and the amount of time missed from work due to migraine. Scores are based on a percentage, so the range of scores is 0-100%, with higher scores indicating greater impairment and less productivity. Change = (Applicable Treatment Month Score - Baseline Score)

Outcome measures

Measure	AJOVY (Fremanezumab-vfrm) - Responder n=21 Participants Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks. Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution \[AJOVY\]: 225 MG/1.5 ML Subcutaneous Solution Participants meeting the 50% response criteria (responders) were identified using participants' self-reported data. Responders for the purpose of this study are defined as any participant with ≥ 50% reduction in the number of migraines from baseline to at least 2 out of the 3 treatment periods.	AJOVY (Fremanezumab-vfrm) - Non-Responder n=19 Participants Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks. Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution \[AJOVY\]: 225 MG/1.5 ML Subcutaneous Solution Participants not meeting the 50% response criteria (non-responders) were identified using participants' self-reported data. Non-responders for the purpose of this study are defined as any participant with \< 50% reduction in the number of migraines from baseline to at least 2 out of the 3 treatment periods.
Change in Work Productivity and Activity Impairment - Migraine (WPAI-M) Activity Impairment Scores From Baseline to Weeks 4, 8, and 12. Week 4	-20.48 score on a scale Standard Deviation 25.39	-5.26 score on a scale Standard Deviation 23.66
Change in Work Productivity and Activity Impairment - Migraine (WPAI-M) Activity Impairment Scores From Baseline to Weeks 4, 8, and 12. Week 8	-26.19 score on a scale Standard Deviation 24.59	-7.90 score on a scale Standard Deviation 26.99
Change in Work Productivity and Activity Impairment - Migraine (WPAI-M) Activity Impairment Scores From Baseline to Weeks 4, 8, and 12. Week 12	-24.76 score on a scale Standard Deviation 37.77	-14.21 score on a scale Standard Deviation 20.90

SECONDARY outcome

Timeframe: Baseline to Weeks 4, 8, and 12

Population: All participants enrolled and with at least one administration of investigational product (IP), will be included in this study population. The Full Analysis Population will be used to analyze the efficacy and safety endpoints.

The Brief Measure of Worry Severity (BMWS) is a 8-item, self-administered questionnaire that measures various components of dysfunctional worry. Score range from 0-24 with higher scores indicating more worry within the participant. Change = (Applicable Treatment Month Score - Baseline Score)

Outcome measures

Measure	AJOVY (Fremanezumab-vfrm) - Responder n=21 Participants Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks. Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution \[AJOVY\]: 225 MG/1.5 ML Subcutaneous Solution Participants meeting the 50% response criteria (responders) were identified using participants' self-reported data. Responders for the purpose of this study are defined as any participant with ≥ 50% reduction in the number of migraines from baseline to at least 2 out of the 3 treatment periods.	AJOVY (Fremanezumab-vfrm) - Non-Responder n=19 Participants Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks. Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution \[AJOVY\]: 225 MG/1.5 ML Subcutaneous Solution Participants not meeting the 50% response criteria (non-responders) were identified using participants' self-reported data. Non-responders for the purpose of this study are defined as any participant with \< 50% reduction in the number of migraines from baseline to at least 2 out of the 3 treatment periods.
Change in Brief Measure of Worry Severity (BMWS) Scores From Baseline to Weeks 4, 8, and 12. Week 4	-0.57 score on a scale Standard Deviation 2.87	-0.05 score on a scale Standard Deviation 3.10
Change in Brief Measure of Worry Severity (BMWS) Scores From Baseline to Weeks 4, 8, and 12. Week 8	-0.91 score on a scale Standard Deviation 2.53	-0.68 score on a scale Standard Deviation 4.80
Change in Brief Measure of Worry Severity (BMWS) Scores From Baseline to Weeks 4, 8, and 12. Week 12	-1.05 score on a scale Standard Deviation 2.33	-1.63 score on a scale Standard Deviation 5.86

Adverse Events

AJOVY (Fremanezumab-vfrm)

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	AJOVY (Fremanezumab-vfrm) n=40 participants at risk Participants received 225 mg/1.5 mL solution via single-dose prefilled syringe administered subcutaneously once every 4 weeks in the abdomen, thigh, or upper arm for 12 weeks. Fremanezumab-Vfrm 225 MG/1.5 ML Subcutaneous Solution \[AJOVY\]: 225 MG/1.5 ML Subcutaneous Solution
Nervous system disorders Dizziness	7.5% 3/40 • Number of events 4 • 12 weeks
Infections and infestations Gastroenteritis	5.0% 2/40 • Number of events 2 • 12 weeks
General disorders Injection site reaction	12.5% 5/40 • Number of events 8 • 12 weeks
Gastrointestinal disorders Nausea	5.0% 2/40 • Number of events 3 • 12 weeks
Musculoskeletal and connective tissue disorders Neck pain	5.0% 2/40 • Number of events 2 • 12 weeks

Additional Information

Jim Sly

Clinvest Research

Phone: 417-841-3673

Email: jsly@clinvest.com

Results disclosure agreements

• Principal investigator is a sponsor employee The investigator agrees to submit all manuscripts or abstracts to sponsor before submission. Sponsor will comply with the requirements for publication of study results. In accordance with standard editorial and ethical practice, the sponsor will generally support publication of multicenter studies only in their entirety and not as individual site data. In this case, a coordinating investigator will be designated by mutual agreement.
• Publication restrictions are in place

Restriction type: OTHER