Trigeminal Neuralgia

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.

BIIB074

BIIB074

tablet

150mg/tablet、250mg/tablet

The primary endpoint that relates to this objective is the
proportion of subjects with a response in average daily pain
(ADP) at Week 12 of the double-blind period.
A subject who meets all of the following criteria will be
classified as a responder:
 has a reduction of ≥30% in weekly mean ADP at
Week 12 of the double-blind period compared with
baseline (run-in);
 has not discontinued randomized treatment; and
 has not taken TN medications other than
acetaminophen/paracetamol during the double-blind
period
A subject who fails to meet 1 or more of these criteria will
be classified as a nonresponder.
Secondary endpoints that relate to the primary objective are
as follows:
1. Time from randomization to loss of therapeutic
response (LOTR).
Subjects who are nonresponders at Week 12 of the
double-blind period will be classified as having a
LOTR. Time of LOTR will be the first week during
the double-blind period that a subject meets the
definition of nonresponder.
2. Change from baseline to Week 12 of the doubleblind period in weekly mean ADP.
3. Proportion of subjects with a response in number of
paroxysms at Week 12 of the double-blind period.
A subject who meets all of the following criteria will
be classified as a responder:
 has a reduction of ≥30% in weekly mean of
number of paroxysms at Week 12 of the
double-blind period compared with baseline
(run-in);
 has not discontinued randomized treatment;
and
 has not taken TN medications other than
acetaminophen/paracetamol during the
double blind period
A subject who fails to meet 1 or more of these
criteria will be classified as a nonresponder.
4. Proportion of subjects with a Patient Global
Impression of Change (PGIC) response at Week 12
of the double-blind period.
A subject who meets all of the following criteria will
be classified as a responder:
 has a PGIC response of “much improved” or
“very much improved” at Week 12 of the
double-blind period;
 has not discontinued randomized treatment;
and
 has not taken TN medications other than
acetaminophen/paracetamol during the
double-blind period
A subject who fails to meet 1 or more of these
criteria will be classified as a nonresponder.
5. Change from baseline to Week 12 of the
double-blind period in the Penn Facial Pain Scale-Revised (PENN-FPS-R) score.
Other endpoints that relate to the primary objective are as
follows:
 Change from baseline to Week 12 of the
double-blind period in weekly mean of number of
paroxysms.
 Proportion of subjects with a response at Week 12 of
the double-blind period based on ≥50% reduction in
weekly mean ADP compared with baseline.
Subjects who discontinue study treatment
prematurely or take TN medications other than
acetaminophen/paracetamol during the double-blind
period will be classified as nonresponders.
 Proportion of subjects with a response at Week 12 of
the double-blind period based on ≥50% reduction in
weekly mean of number of paroxysms compared
with baseline. Subjects who discontinue study
treatment prematurely or take TN medications other
than acetaminophen/paracetamol during the doubleblind period will be classified as nonresponders.
 Amount of rescue medication
(acetaminophen/paracetamol) used per day for TN
pain during the double-blind period.
 Proportion of subjects taking rescue medication
(acetaminophen/paracetamol) for TN pain during the
double-blind period.
 Change from baseline in weekly mean ADP at each
week during the double-blind period.
 Change from baseline in weekly mean of number of
paroxysms at each week during the double-blind
period.
For the efficacy endpoints based on daily subject diary,
baseline will be defined as the mean of the scores over the
7 days preceding the first dose of study treatment in the
open-label period. Subjects with fewer than 5 scores will be
considered to have a missing baseline.
For other efficacy endpoints, baseline will be the last
measurement before the first dose of study treatment.

Inclusion Criteria
To be eligible to participate in this study, candidates must meet the following eligibility criteria
on Day 1 (start of the open-label period), or at the timepoint specified in the individual eligibility
criterion listed:
1. Ability of the subject to understand the purpose and risks of the study and provide signed
and dated informed consent and authorization to use confidential health information in
accordance with national and local subject privacy regulations.
2. Age ≥18 years old at the time of informed consent.
3. All women of childbearing potential who have been amenorrheic for less than 1 year and
all men must practice effective contraception during the study. Effective contraception
must be continued after the last dose of study treatment for 5 weeks by women and for
14 weeks by men. For further details of contraceptive requirements for this study, please
refer to Section 15.5.
4. A diagnosis of TN for at least 3 months based on IHS diagnostic criteria. The diagnosis
will be reviewed and confirmed by 2 members of the diagnostic subcommittee before
enrollment.
5. IHS criteria for the International Classification of Headache Disorders (ICHD) 3rd edition
(beta version) (13.1.1.1) for classical TN, purely paroxysmal, must be met:
A. At least 3 attacks of unilateral facial pain fulfilling criteria B and C
B. Occurring in 1 or more divisions of the trigeminal nerve, with no radiation beyond the
trigeminal distribution
C. Pain has at least 3 of the following 4 characteristics:
1. recurring paroxysmal attacks lasting from a fraction of a second to 2 minutes
2. severe intensity
3. electric shock-like, shooting, stabbing, or sharp in quality
4. precipitated by innocuous stimuli to the affected side of the face
D. No clinically evident neurological deficit
E. Not better accounted for by another ICHD-3 diagnosis
6. Subjects must have suffered a minimum of 3 paroxysms of TN pain per day, with a
weekly mean ADP rating between 4 and 8 on the 11-point NRS during the run-in period
(Days -7 to -1).
7. Subject 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.
8. Subjects must have recorded their ADP in their eDiary on at least 5 days during the runin period (Days -7 to -1).
9. Allowed concomitant medications must have been stable for at least 3 weeks prior to
Day 1 of the open-label period. The maximum dose of carbamazepine allowed on Day 1
is 400 mg/day (or 600 mg/day for oxcarbazepine).
10. Subjects who have had microvascular decompression performed for TN but meet all
other entry criteria are eligible for the study.

Exclusion Criteria
Candidates will be excluded from study entry if any of the following exclusion criteria exist on
Day 1 (start of open-label period) or at the timepoint specified in the individual criterion listed:
Medical History
1. 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]). Subjects with immunity to hepatitis B from
previous natural infection (defined as negative HBsAg, positive hepatitis B surface
antibody [HBsAb] IgG, and positive HBcAb) are eligible to participate in the study (US
Centers for Disease Control and Prevention’s interpretation of the hepatitis B serology
panel).
2. Positive history of human immunodeficiency virus (HIV) or a positive HIV test at
Screening.
3. Subjects with facial pain other than TN.
4. History of any liver disease within the last 6 months, with the exception of known
Gilbert’s disease.
5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >2 × the upper
limit of normal (ULN); alkaline phosphatase and bilirubin ≥1.5 × ULN. (Isolated
increase of bilirubin in fasting condition, consistent with Gilbert’s syndrome, is
acceptable.)
6. History of alcohol or substance abuse, as determined by the Investigator.
7. Personal or family (first-degree relative) history of seizures (except for simple febrile
convulsions) or clinically significant head injury.
8. History of uncontrolled or poorly controlled hypertension, with systolic blood pressure
frequently exceeding 160 mmHg and/or diastolic blood pressure frequently exceeding
100 mmHg, or systolic blood pressure ≥160 mmHg or diastolic blood pressure
≥100 mmHg at sScreening after repeated measurements.
9. History or presence of significant cardiovascular, gastrointestinal, or renal disease or
other condition known to interfere with the absorption, distribution, metabolism, or
excretion of drug.
10. Fridericia’s correction method (QTcF) >450 msec (males) or >460 msec (females)
[average of 3 ECGs conducted at sScreening].
11. Presence of conditions known to affect cardiac conduction, or a personal or familial
history of Brugada syndrome.
12. History or presence of any clinically significant abnormality in vital signs, ECG, or
laboratory tests or have any medical or psychiatric condition, which, in the opinion of the
Investigator, may interfere with the study procedures or compromise patient safety.
13. History of suicide attempt within 6 months prior to screening, or a positive response to
item 4 or 5 of the C-SSRS.
14. Episode of major depression within the last 6 months prior to screening (clinically stable
minor depression is not exclusionary).
15. MRI demonstrating an etiology other than vascular compression for TN (e.g., multiple
sclerosis, tumor).
Note: MRI must be available to rule out causes of TN other than vascular compression.
If not available from the subject’s medical records, an MRI should be performed locally
during screening.
16. Subjects with contraindications for MRI (e.g., metallic implants) if required at Screening
to confirm a diagnosis of TN.
Medications and Procedures
17. Previous exposure to BIIB074 (formerly known as CNV1014802 or GSK1014802).
18. Unable or unwilling to discontinue concomitant medications for TN during the run-in and
open-label periods of the study (see Section 11.5.1.2).
19. Unable to refrain from excessive use of sedatives.
20. Unable or unwilling to comply with the prohibited concomitant medication restrictions as
detailed in the list of excluded medications in Section 11.5.1.2, cytochrome P450 3A4
(CYP3A4) and uridine 5'-diphospho-glucuronosyltransferase (UGT) inducers and
inhibitors, and monoamine oxidase inhibitors (MAOIs).
21. Use of over-the-counter medications, vitamin and mineral supplements, herbal remedies
(including St. John’s Wort), dietary supplements, or foods (including grapefruit juice)
that affect CYP3A and UGTs.
22. Subject has had an ablative procedure(s) for TN.
Other
23. Pregnant or lactating females.
24. Participation in a clinical trial within 3 months, and received an investigational product
within 5 half-lives or twice the duration of the biological effect of the investigational
product (whichever is longer) prior to the start of this study.
25. Subject is mentally or legally incapacitated.
26. Current enrollment in any other study treatment or disease study.
27. Inability to comply with study requirements.
28. Other unspecified reasons that, in the opinion of the Investigator or Biogen, make the
subject unsuitable for enrollment.