Back to results802NP302 Efficacy and Safety Study of BIIB074 in Participants With Trigeminal Neuralgia (SURGE-2)
Primary Purpose
Trigeminal Neuralgia
Status
Withdrawn
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
BIIB074
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Trigeminal Neuralgia focused on measuring TGN, TN
Eligibility Criteria
Key Inclusion Criteria:
- A diagnosis of trigeminal neuralgia (TN) for at least 3 months based on International Headache Society (IHS) diagnostic criteria.
- Participant must have failed at least 1 prior standard of care pharmacologic treatment for TN (defined as an inadequate response or intolerance to treatment), as determined by the Investigator based on medical history.
- Age ≥18 years at the time of informed consent.
- Participants must have recorded their pain score in their eDiary on at least 5 days during the run-in period (Days -7 to -1).
- Allowed concomitant medications must have been stable for at least 4 weeks prior to Day 1 of the dose-optimization period. The maximum dosage of carbamazepine allowed on Day 1 is 400 mg/day (or 600 mg/day for oxcarbazepine).
Key Exclusion Criteria:
- History or positive test result at Screening for hepatitis C virus antibody or current hepatitis B infection (defined as positive for hepatitis B surface antigen [HBsAg] and/or hepatitis B core antibody [HBcAb]).
- Positive history of human immunodeficiency virus (HIV) or a positive HIV test at Screening.
- Participants with facial pain other than TN.
- Personal or family (first-degree relative) history of seizures (except for simple febrile convulsions) or clinically significant head injury.
- Positive drug screen for drugs of abuse at Screening (amphetamine [methamphetamines and 3,4-methylenedioxymethamphetamine], phencyclidine, barbiturates, benzodiazepines, cocaine, opioids) except if explained by use of allowed prescription medicines. Prospective subjects with a positive screen for tetrahydrocannabinol must agree to discontinue use upon study enrollment and for the duration of the study.
- Known hypersensitivity to BIIB074 or components of the BIIB074 formulation or matching placebo.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
BIIB074
Placebo
Arm Description
Administered orally three times daily (TID)
Placebo matching BIIB074
Outcomes
Primary Outcome Measures
Percentage of Participants Classified as Responders at Week 12 of the Double- Blind Period
A participant who meets all of the following criteria will be classified as a responder: (1) Has a reduction of >=30% in mean pain score compared with baseline; (2) Has not discontinued randomized treatment before the end of Week 12 of the double-blind period; (3) Has not taken prohibited pain medication before the end of Week 12 of the double-blind period.
Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Long Term Extension (LTE) Period
An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE was defined as any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the subject at immediate risk of death (a life-threatening event; however, this does not include an event that, had it occurred in a more severe form, might have caused death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or results in a congenital anomaly/birth defect.
Secondary Outcome Measures
Percentage of Participants Classified as Responders Achieving Patient Global Impression of Change (PGIC) Response at Week 12 of the Double-Blind Period
A participant who meets all of the following criteria will be classified as a responder: (1) Achieving Patient Global Impression of Change (PGIC) response of "Much Improved" or "Very Much Improved" at Week 12 of the double-blind period; (2) has not discontinued randomized study treatment before the end of Week 12 of the double-blind period; (3) has not taken prohibited pain medication before the end of Week 12 of the double-blind period. PGIC is a 7-item self-report scale depicting a participant's rating of overall improvement. Participants rate their change as "very much improved," "much improved," "minimally improved," "no change," "minimally worse," "much worse," or "very much worse."
Percentage of Participants Classified as Responders Achieving >=50 Percent Reduction From Baseline Mean Number of Paroxysms at Week 12
A participant who meets all of the following criteria will be classified as a responder: (1) Achieving >=50 percent reduction from baseline mean number of paroxysms at Week 12; (2) has not discontinued randomized study treatment before the end of Week 12 of the double-blind period; (3) has not taken prohibited pain medication before the end of Week 12 of the double-blind period. A paroxysm is a trigeminal neuralgia pain attack.
Percentage of Participants Classified as Responders Achieving >=50 Percent Reduction From Baseline Mean Pain Score at Week 12
A participant who meets all of the following criteria will be classified as a responder: (1) Achieving >=50 percent reduction from baseline mean pain score at Week 12; (2) has not discontinued randomized study treatment before the end of Week 12 of the double-blind period; (3) has not taken prohibited pain medication before the end of Week 12 of the double-blind period. Pain score is a 11-point numerical rating scale where 0 = no pain; 10 = maximum pain imaginable. Higher scores representing more pain.
Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Double Blind Period
An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE was defined as any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the subject at immediate risk of death (a life-threatening event; however, this does not include an event that, had it occurred in a more severe form, might have caused death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or results in a congenital anomaly/birth defect.
Area Under the Plasma Concentration- Time Curve at Steady State (AUC,ss)
AUC,ss= Area under the plasma concentration versus time curve (AUC) at steady state.
Maximum Observed Plasma Concentration at Steady State (Cmax,ss)
Cmax,ss= Maximum Observed Plasma Concentration of BIIB074 at Steady State
Percentage of Participants with >=30% Reduction From Baseline in Mean Pain Score During the Long Term Extension (LTE) Period
Pain score is a 11-point numerical rating scale where 0 = no pain; 10 = maximum pain imaginable. Higher scores representing more pain.
Change From Baseline in Mean Pain Score During the Long Term Extension (LTE) Period
Pain score is a 11-point numerical rating scale where 0 = no pain; 10 = maximum pain imaginable. Higher scores representing more pain.
Change From Baseline in Mean Worst Pain Score During the Long Term Extension (LTE) Period
Pain score is a 11-point numerical rating scale where 0 = no pain; 10 = maximum pain imaginable. Higher scores representing more pain.
Percentage of Participants with >=50% Reduction From Baseline in Mean Number of Paroxysms During Long Term Extension (LTE) Period
Paroxysms are trigeminal neuralgia pain attacks. They are short, severe, and sharp, shooting, stabbing, or shock-like.
Change From Baseline in Mean Number of Paroxysms During Long Term Extension (LTE) Period
Paroxysms are trigeminal neuralgia pain attacks. They are short, severe, and sharp, shooting, stabbing, or shock-like.
Percentage of Participants With a PGIC Response of "Much Improved or "Very Much Improved" by Visit During the Long Term Extension (LTE) Period
PGIC is a 7-point self-report scale depicting a participant's rating of overall improvement. Participants rate their change as "very much improved," "much improved," "minimally improved," "no change," "minimally worse," "much worse," or "very much worse." Participants with "Much Improved or "Very Much Improved" will be reported.
Change From Baseline in the PENN-FPS-R Score by Visit During the Long Term Extension (LTE) Period
The Penn-FPS-R is a new 12-item Health-Related Quality of Life outcome measure with content validity that can be used to assess and monitor the impact of Trigeminal Neuralgia and facial pain treatment interventions in both clinical practice and research. This scale uses the 0-10 numeric rating scale (NRS) to quantify the pain impact different activities and quality of life items, where 0 indicates no interference and 10 indicates complete interference. The sum of the rated NRS score will be calculated.
Change From Baseline in the EQ-5D-5L Score by Visit During the Long Term Extension (LTE) Period
EQ-5D-5L is a standardized, subject-rated instrument for use as a measure of health outcomes. The EQ 5D-5L includes 2 components: the EQ-5D-5L descriptive system and the EQ-Visual Analog Scale (EQ-VAS). The EQ-5D-5L descriptive system provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each dimension, the participant is instructed to indicate whether he or she has no problems, slight problems, moderate problems, severe problems, and extreme problems. A negative change from Baseline indicates improvement.
Change From Baseline in the WPAI Neuropathic Pain (V2.0) Score by Visit During the Long Term Extension (LTE) Period
The WPAI questionnaire is a validated instrument to measure impairments in work and activities. The WPAI yields four types of scores: 1. Absenteeism (percentage of work time missed) 2. Presenteeism (percentage of impairment at work/reduced on-the-job effectiveness) 3. Work productivity loss (percentage of overall work impairment [absenteeism plus presenteeism]) 4. Activity Impairment (percentage of overall activity impairment). WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03637387
Brief Title
802NP302 Efficacy and Safety Study of BIIB074 in Participants With Trigeminal Neuralgia
Acronym
SURGE-2
Official Title
A Phase 3 Placebo-Controlled, Double-Blind Randomized Withdrawal Study to Evaluate the Efficacy and Safety of BIIB074 in Subjects With Trigeminal Neuralgia
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Withdrawn
Why Stopped
Sponsor Decision
Study Start Date
March 1, 2023 (Anticipated)
Primary Completion Date
August 18, 2025 (Anticipated)
Study Completion Date
September 29, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biogen
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary objective of the study is to evaluate the efficacy of BIIB074 in treating pain experienced by participants with trigeminal neuralgia (TN).
The secondary objectives are to investigate the safety and tolerability of BIIB074 in participants with TN and to evaluate the population pharmacokinetic(s) (PK) of BIIB074.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Trigeminal Neuralgia
Keywords
TGN, TN
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
BIIB074
Arm Type
Experimental
Arm Description
Administered orally three times daily (TID)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo matching BIIB074
Intervention Type
Drug
Intervention Name(s)
BIIB074
Intervention Description
Administered as specified in the treatment arm
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Administered as specified in the treatment arm.
Primary Outcome Measure Information:
Title
Percentage of Participants Classified as Responders at Week 12 of the Double- Blind Period
Description
A participant who meets all of the following criteria will be classified as a responder: (1) Has a reduction of >=30% in mean pain score compared with baseline; (2) Has not discontinued randomized treatment before the end of Week 12 of the double-blind period; (3) Has not taken prohibited pain medication before the end of Week 12 of the double-blind period.
Time Frame
Week 12
Title
Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Long Term Extension (LTE) Period
Description
An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE was defined as any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the subject at immediate risk of death (a life-threatening event; however, this does not include an event that, had it occurred in a more severe form, might have caused death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or results in a congenital anomaly/birth defect.
Time Frame
Baseline up to Week 52 of the LTE
Secondary Outcome Measure Information:
Title
Percentage of Participants Classified as Responders Achieving Patient Global Impression of Change (PGIC) Response at Week 12 of the Double-Blind Period
Description
A participant who meets all of the following criteria will be classified as a responder: (1) Achieving Patient Global Impression of Change (PGIC) response of "Much Improved" or "Very Much Improved" at Week 12 of the double-blind period; (2) has not discontinued randomized study treatment before the end of Week 12 of the double-blind period; (3) has not taken prohibited pain medication before the end of Week 12 of the double-blind period. PGIC is a 7-item self-report scale depicting a participant's rating of overall improvement. Participants rate their change as "very much improved," "much improved," "minimally improved," "no change," "minimally worse," "much worse," or "very much worse."
Time Frame
Week 12
Title
Percentage of Participants Classified as Responders Achieving >=50 Percent Reduction From Baseline Mean Number of Paroxysms at Week 12
Description
A participant who meets all of the following criteria will be classified as a responder: (1) Achieving >=50 percent reduction from baseline mean number of paroxysms at Week 12; (2) has not discontinued randomized study treatment before the end of Week 12 of the double-blind period; (3) has not taken prohibited pain medication before the end of Week 12 of the double-blind period. A paroxysm is a trigeminal neuralgia pain attack.
Time Frame
Week 12
Title
Percentage of Participants Classified as Responders Achieving >=50 Percent Reduction From Baseline Mean Pain Score at Week 12
Description
A participant who meets all of the following criteria will be classified as a responder: (1) Achieving >=50 percent reduction from baseline mean pain score at Week 12; (2) has not discontinued randomized study treatment before the end of Week 12 of the double-blind period; (3) has not taken prohibited pain medication before the end of Week 12 of the double-blind period. Pain score is a 11-point numerical rating scale where 0 = no pain; 10 = maximum pain imaginable. Higher scores representing more pain.
Time Frame
Week 12
Title
Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Double Blind Period
Description
An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE was defined as any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the subject at immediate risk of death (a life-threatening event; however, this does not include an event that, had it occurred in a more severe form, might have caused death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or results in a congenital anomaly/birth defect.
Time Frame
Up to Week 14 of Double blind period
Title
Area Under the Plasma Concentration- Time Curve at Steady State (AUC,ss)
Description
AUC,ss= Area under the plasma concentration versus time curve (AUC) at steady state.
Time Frame
Day 15, 29, 43, 57, 71, 85, 99, 113, 127, 141, premature treatment discontinuation (if occurred)
Title
Maximum Observed Plasma Concentration at Steady State (Cmax,ss)
Description
Cmax,ss= Maximum Observed Plasma Concentration of BIIB074 at Steady State
Time Frame
Day 15, 29, 43, 57, 71, 85, 99, 113, 127, 141, premature treatment discontinuation (if occurred)
Title
Percentage of Participants with >=30% Reduction From Baseline in Mean Pain Score During the Long Term Extension (LTE) Period
Description
Pain score is a 11-point numerical rating scale where 0 = no pain; 10 = maximum pain imaginable. Higher scores representing more pain.
Time Frame
Week 1 through Week 52
Title
Change From Baseline in Mean Pain Score During the Long Term Extension (LTE) Period
Description
Pain score is a 11-point numerical rating scale where 0 = no pain; 10 = maximum pain imaginable. Higher scores representing more pain.
Time Frame
Baseline, Week 1 through Week 52
Title
Change From Baseline in Mean Worst Pain Score During the Long Term Extension (LTE) Period
Description
Pain score is a 11-point numerical rating scale where 0 = no pain; 10 = maximum pain imaginable. Higher scores representing more pain.
Time Frame
Baseline, Week 1 through Week 52
Title
Percentage of Participants with >=50% Reduction From Baseline in Mean Number of Paroxysms During Long Term Extension (LTE) Period
Description
Paroxysms are trigeminal neuralgia pain attacks. They are short, severe, and sharp, shooting, stabbing, or shock-like.
Time Frame
Week 1 through Week 52
Title
Change From Baseline in Mean Number of Paroxysms During Long Term Extension (LTE) Period
Description
Paroxysms are trigeminal neuralgia pain attacks. They are short, severe, and sharp, shooting, stabbing, or shock-like.
Time Frame
Baseline, Week 1 through Week 52
Title
Percentage of Participants With a PGIC Response of "Much Improved or "Very Much Improved" by Visit During the Long Term Extension (LTE) Period
Description
PGIC is a 7-point self-report scale depicting a participant's rating of overall improvement. Participants rate their change as "very much improved," "much improved," "minimally improved," "no change," "minimally worse," "much worse," or "very much worse." Participants with "Much Improved or "Very Much Improved" will be reported.
Time Frame
Day 1, Week 2, 4, 6, 8, every 12 weeks up to Week 52
Title
Change From Baseline in the PENN-FPS-R Score by Visit During the Long Term Extension (LTE) Period
Description
The Penn-FPS-R is a new 12-item Health-Related Quality of Life outcome measure with content validity that can be used to assess and monitor the impact of Trigeminal Neuralgia and facial pain treatment interventions in both clinical practice and research. This scale uses the 0-10 numeric rating scale (NRS) to quantify the pain impact different activities and quality of life items, where 0 indicates no interference and 10 indicates complete interference. The sum of the rated NRS score will be calculated.
Time Frame
Baseline, Day 1, Week 2, 4, 6, 8, every 12 weeks up to Week 52
Title
Change From Baseline in the EQ-5D-5L Score by Visit During the Long Term Extension (LTE) Period
Description
EQ-5D-5L is a standardized, subject-rated instrument for use as a measure of health outcomes. The EQ 5D-5L includes 2 components: the EQ-5D-5L descriptive system and the EQ-Visual Analog Scale (EQ-VAS). The EQ-5D-5L descriptive system provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each dimension, the participant is instructed to indicate whether he or she has no problems, slight problems, moderate problems, severe problems, and extreme problems. A negative change from Baseline indicates improvement.
Time Frame
Baseline, Day 1, Week 4, 8, every 12 weeks up to Week 52
Title
Change From Baseline in the WPAI Neuropathic Pain (V2.0) Score by Visit During the Long Term Extension (LTE) Period
Description
The WPAI questionnaire is a validated instrument to measure impairments in work and activities. The WPAI yields four types of scores: 1. Absenteeism (percentage of work time missed) 2. Presenteeism (percentage of impairment at work/reduced on-the-job effectiveness) 3. Work productivity loss (percentage of overall work impairment [absenteeism plus presenteeism]) 4. Activity Impairment (percentage of overall activity impairment). WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity.
Time Frame
Baseline, Day 1, Week 4, 8, every 12 weeks up to Week 52
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
A diagnosis of trigeminal neuralgia (TN) for at least 3 months based on International Headache Society (IHS) diagnostic criteria.
Participant must have failed at least 1 prior standard of care pharmacologic treatment for TN (defined as an inadequate response or intolerance to treatment), as determined by the Investigator based on medical history.
Age ≥18 years at the time of informed consent.
Participants must have recorded their pain score in their eDiary on at least 5 days during the run-in period (Days -7 to -1).
Allowed concomitant medications must have been stable for at least 4 weeks prior to Day 1 of the dose-optimization period. The maximum dosage of carbamazepine allowed on Day 1 is 400 mg/day (or 600 mg/day for oxcarbazepine).
Key Exclusion Criteria:
History or positive test result at Screening for hepatitis C virus antibody or current hepatitis B infection (defined as positive for hepatitis B surface antigen [HBsAg] and/or hepatitis B core antibody [HBcAb]).
Positive history of human immunodeficiency virus (HIV) or a positive HIV test at Screening.
Participants with facial pain other than TN.
Personal or family (first-degree relative) history of seizures (except for simple febrile convulsions) or clinically significant head injury.
Positive drug screen for drugs of abuse at Screening (amphetamine [methamphetamines and 3,4-methylenedioxymethamphetamine], phencyclidine, barbiturates, benzodiazepines, cocaine, opioids) except if explained by use of allowed prescription medicines. Prospective subjects with a positive screen for tetrahydrocannabinol must agree to discontinue use upon study enrollment and for the duration of the study.
Known hypersensitivity to BIIB074 or components of the BIIB074 formulation or matching placebo.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Biogen
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
IPD Sharing URL
https://vivli.org/
Learn more about this trial
802NP302 Efficacy and Safety Study of BIIB074 in Participants With Trigeminal Neuralgia
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