| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Treating Pain Experienced by Subjects With Confirmed Small Fibre Neuropathy That is Idiopathic or
Associated With Diabetes Mellitus |
|
| E.1.1.1 | Medical condition in easily understood language |
| Neurapathic pain caused by unknown reasons or by diabetes |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10073928 |
| E.1.2 | Term | Small fibre neuropathy |
| E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective of this study is to evaluate the efficacy of BIIB074 in treating pain experienced by subjects with confirmed small fibre neuropathy (SFN) that is idiopathic or associated with diabetes mellitus. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to evaluate the effect on worst pain, neuropathic pain quality, sleep interference due to pain, patient global impression, use of supplemental pain medication, and SFN symptoms in participants treated with BIIB074; to investigate the
safety and tolerability of BIIB074 in participants with SFN; and to characterize the pharmacokinetics (PK) of BIIB074 in participants with SFN. |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Corneal Confocal Microscopy (CCM) as a Screening, Predictive, and
Surrogate Endpoint Biomarker for study 802NP206: A Phase 2 Placebo-
Controlled, Double-Blind, Enriched Enrollment Randomized Withdrawal
Study to Evaluate the Efficacy and Safety of BIIB074 in Treating Pain
Experienced by Subjects With Confirmed Small Fibre Neuropathy That is
Idiopathic or Associated With Diabetes Mellitus.
Exploratory Objectives
To evaluate the relationship of quantitative corneal nerve morphology
via CCM with SFN diagnosis.
To evaluate the relationship of quantitative corneal nerve morphology
via CCM with initial response to BIIB074.
To evaluate the relationship of quantitative corneal nerve morphology
via CCM with response to continued BIIB074 treatment or placebo for 12
weeks. |
|
| E.3 | Principal inclusion criteria |
Key Inclusion Criteria:
1. This study will be conducted in subjects who have had a diagnosis of at least probable SFN length-dependent distribution for ≥6 months and
≤10 years , based on clinical diagnosis and confirmed by intraepidermal nerve fibre density (IENFD) values, and weekly mean average daily pain (ADP) score of ≥5 and ≤9 on an 11-point Pain Intensity Numeric Rating Scale (PI-NRS) over the last 7 days of Screening.
2. In addition to these criteria, subjects with diabetes will be required to have HbA1c ≤11%, treated with oral hypoglycemics and/or subcutaneous insulin or diet, no evidence of ulcers, advanced retinopathy (defined as greater than State 3 [moderate non-proliferative diabetic retinopathy]) (DCCT/EDIC Research Group 2017), severe nephropathy, or clinically significant obstructive atherosclerotic disease (e.g., current unstable angina or myocardial infarction within 6 months of Screening), or current class IV heart failure to be eligible for the study.
NOTE: Other protocol defined Inclusion criteria may apply |
|
| E.4 | Principal exclusion criteria |
Key Exclusion Criteria:
1. Previous exposure to BIIB074 (formerly known as CNV1014802 or GSK1014802).
2. Use of capsaicin patch within 3 months prior to Screening.
3. Unable or unwilling to discontinue concomitant medications for neuropathic pain during the 2 week
taper period, which overlaps the first week of the openlabel run-in period.
4. Unable or unwilling to comply with the prohibited concomitant medication restrictions, including but not limited to UDPglucuronosyltransferase
(UGT) inducers and inhibitors, monoamine oxidase inhibitors (MAOIs), and Nav blockers.
5. 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 UGTs.
6. Unable or unwilling to discontinue medications that are P-glycoprotein substrates with a narrow therapeutic
index, including but not limited to digoxin.
7. History of hemophilia or Von Willebrand’s disease, or use of anticoagulants that may result in bleeding risk during the skin biopsy.
8. Any contraindication, as determined by the Investigator, to performing a skin biopsy for intraepidermal nerve fibre analysis.
9. Current hepatitis C infection (defined as positive hepatitis C virus [HCV] antibody and detectable HCV ribonucleic acid [RNA]). Participants with positive HCV antibody and undetectable HCV RNA are eligible to participate in the study (United States Centers for Disease Control and Prevention).
NOTE: Other protocol defined Exclusion criteria may apply |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1. Change from Baseline in Weekly Mean Average Daily Pain (ADP) Score:
Participants will rate their ADP using an 11-point Numerical Rating Scale (NRS) (0=no pain and 10=worst possible pain) and record their score in an electronic diary (eDiary). Weekly mean ADP scores for Baseline (the 7 days prior to the first dose of study treatment in the open-label
run-in period) and Week 12 (the 7 days prior to the visit at the end of Week 12) will be derived from the ADP scores and calculated as the mean of the daily scores over the last
7 days.
2. Change from Randomization in Weekly Mean ADP Score:
Participants will rate their ADP using an 11-point NRS (0=no pain and 10=worst possible pain) and record their score in an eDiary. Weekly mean ADP scores for Randomization (the 7 days prior to the first dose of
study treatment in the doubleblind
period) and Week 12 (the 7 days prior to the visit at the end of Week 12) will be derived from the ADP scores and calculated as the mean of
the daily scores over the last
7 days. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Baseline and Week 12 of the Double-Blind Period
2. Day 78 to 84 of the Double-Blind Period |
|
| E.5.2 | Secondary end point(s) |
1. Change from Baseline in Weekly Mean Worst Daily Pain (WDP) Score:
Participants will rate their WDP using
an 11-point NRS (0=no pain and 10=worst possible pain) and record
their score in an eDiary. Weekly mean WDP scores for Baseline (the
7 days prior to the first dose of study
treatment in the open-label run-in
period) and Week 12 (the 7 days
prior to the visit at the end of Week
12) will be derived from the WDP
scores and calculated as the mean
of the daily scores over the last 7
days.
2. Change from Baseline in Weekly Mean Sleep Interference Numerical
Rating Scale (S-NRS):
Participants will rate their S-NRS using an 11-point NRS (0=pain does
not interfere with sleep and 10= pain completely interferes with sleep) and
record their score in an eDiary. Weekly mean S-NRS scores for Baseline (the 7 days prior to the first dose of study treatment in the openlabel run-in period) and Week 12
(the 7 days prior to the visit at the end of Week 12) will be derived from
the daily S-NRS scores and calculated as the mean of the daily scores over the last 7 days.
3. Change from Baseline in Neuropathic Pain Symptom Inventory (NPSI) Total Score and Sum Score:
Participant will use the NPSI questionnaire to rate different symptoms of neuropathic pain. The NPSI includes ten items related to different pain descriptors (e.g.
burning and pressure) that are rated
on an 11-point NRS (0=no symptoms
to 10=worst symptoms imaginable).
A score in each dimension and also
a total score (from 0-100) is generated using data from the
questionnaire.
4. Percentage of Participants with at least a 2-point Reduction from Baseline in Weekly Mean ADP:
Participants will rate their ADP using
an 11-point NRS (0=no pain and 10=worst possible pain) and record
their score in an electronic diary
(eDiary). Weekly mean ADP scores
for Baseline (the 7 days prior to the
first dose of study treatment in the
open-label run-in period) and Week
12 (the 7 days prior to the visit at the
end of Week 12) will be derived from
the ADP scores and calculated as
the mean of the daily scores over the
last 7 days.
5. Percentage of Participants
with at least a 30% Reduction from Baseline in Weekly Mean ADP:
Participants will rate their ADP using
an 11-point NRS) (0=no pain and
10=worst possible pain) and record
their score in an electronic diary
(eDiary). Weekly mean ADP scores
for Baseline (the 7 days prior to the
first dose of study treatment in the
open-label run-in period) and Week
12 (the 7 days prior to the visit at the
end of Week 12) will be derived from
the ADP scores and calculated as the mean of the daily scores over the
last 7 days.
6. Mean Weekly Amount of Supplemental Pain Medication:
Use of supplemental pain medication
(paracetamol/acetaminophen) will be
monitored and dosage will be recorded on a daily basis by the
participant using an electronic Diary
(eDiary). Mean weekly amount of
supplemental pain medication used
for neuropathic pain during the
double-blind period.
7. Patient Global Impression of Change (PGIC):
PGIC is a 7-point self-administered
scale that depicts changes in a participant's overall status. Participants will rate their change as
“1=very much improved,” “2=much
improved,” “3=minimally improved,”
“4=no change,” “5=minimally worse,”
“6=much worse,” or “7=very much
worse.”
8. Change from Baseline in Brief Pain Inventory-Short Form (BPI-SF) Interference Score:
The BPI-SF is a 7-item selfadministered
questionnaire that measures how much pain has interfered with daily functioning. Participants will rate the level of pain interference on daily functioning on an 11-point NRS where 0=does not interfere and 10=completely interferes. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Baseline and Week 12 of the Double-Blind Period
2. Baseline and Week 12 of the Double-Blind Period
3. Baseline and Week 12 of the Double-Blind Period
4. Baseline and Week 12 of the Double-Blind Period
5. Baseline and Week 12 of the Double-Blind Period
6. Weekly from Baseline to Week 12 of the Double- Blind Period
7. Week 12 of the Double- Blind Period
8. Baseline and Week 12 of the Double-Blind Period |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 96 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Bulgaria |
| Canada |
| Czech Republic |
| Denmark |
| France |
| Germany |
| Greece |
| Hungary |
| Italy |
| Netherlands |
| Poland |
| Spain |
| Switzerland |
| United Kingdom |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 11 |
| E.8.9.1 | In the Member State concerned days | 6 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 6 |
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