802NP206 Efficacy and Safety of BIIB074 in Patients with SFN
Research type
Research Study
Full title
A Phase 2 Placebo-Controlled, Double-Blind, Enriched Enrollment\nRandomized 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
IRAS ID
238609
Contact name
Stephen Bain
Contact email
Sponsor organisation
Biogen Idec Research Limited
Eudract number
2017-000991-27
Duration of Study in the UK
2 years, 7 months, 21 days
Research summary
Research Summary
Neuropathic pain is chronic pain caused by injury to or disease of the central and peripheral nervous system (the nervous system outside the brain and spinal cord). Small fibre neuropathy (SFN) is a type of peripheral neuropathy that occurs from damage to the small unmyelinated (nerve fibres that are not covered with a layer of insulation) and thinly myelinated (A-delta) peripheral nerve fibres. These fibres, categorised as C fibres, are present in skin, peripheral nerves, and organs. The features of SFN include severe pain that typically begins in the feet or hands. Other symptoms include burning pain, shooting pain, pain sensitisation, and increased sensitivity. There are no medicines specific for the treatment of pain associated with SFN. The drug being studied in this study, BIIB074, may provide an effective treatment for pain associated with SFN.\nThe main purpose of this study is to evaluate the efficacy (how well the study drug works) and safety (side effects) of BIIB074 compared with placebo in treating pain experienced by subjects with confirmed SFN that is idiopathic or associated with diabetes mellitus. \n\nParticipants will be required to undergo a series of study assessments during the visits including the collection of blood samples and completion of tests to assess pain response and tolerability of treatment. The total duration of the study for each participant will be up to approximately 26 weeks, including a screening and taper period (if applicable) of up to 5 weeks followed by a\n5-day washout period. Subjects will then enter a 4-week open-label run-in period, followed by a\n12-week double-blind period, and a 4 week follow-up period consisting of a Follow-up clinic visit approximately 1 week after the last dose of study treatment and a Follow-up telephone call\n4 weeks after the last dose of study treatment.\nThe study is sponsored by Biogen Idec Research Limited. Around 400 research participants in approximately 10 countries across the world, will take part in this study.
Summary of Results
Biogen
Drug Studied: Vixotrigine (BIIB074)
Protocol Number: 802NP206 (CONVEY)
Study Dates:
Study Start Date: 31 May 2018
Study Completion Date: 12 April 2021
Short Study Title: A Study to Learn About the Safety of Vixotrigine (BIIB074) and Whether it Reduces Pain in People With Painful Small Fiber Neuropathy Due to Diabetes or an Unknown Cause
A clinical study participant belongs to the larger clinical research community around the world.
By participating in a study, they help researchers answer important health questions and learn about new medical drugs.
In this study, researchers learned more about the safety of vixotrigine and if it reduces pain from small fiber neuropathy.
Biogen, the sponsor of this study, thanks those who participated and believes it is important to share the overall results of the study. If you have questions, please speak with the doctor or staff at the study research center.
Why was the study done?
Researchers are looking for new drugs to help people living with painful small fiber neuropathy, also known as SFN.
Neuropathy is a type of damage or dysfunction that affects one or more nerves in the body. This can lead to a type of pain called neuropathic pain. SFN is a type of neuropathy that affects small nerve fibers in the nervous system outside the brain and spinal cord, also known as the peripheral nervous system. Small nerve fibers can be found in the skin where they relay information about pain and temperature to the brain. Many people with SFN experience gradual symptoms that begin in the feet. Pain symptoms can vary and some can be severe. Some of the sensations that may be felt include tingling, burning, or electric shock-like pain.
The cause of SFN varies. Diabetes and prediabetes are often associated with SFN. Other medical conditions have been linked to SFN, however in many cases a cause is unknown.
The study drug, vixotrigine, was designed to potentially help block some signals of nerve pain that the brain receives in people with painful SFN. This study was done to learn more about the safety of vixotrigine and to see if it reduces pain in people with painful SFN. Vixotrigine was compared to placebo, which is an inactive substance that looks like the study drug.
The main questions that the researchers wanted to answer were:
Did taking vixotrigine lower the amount of SFN pain felt by participants after being in the study for about 16 weeks?
What adverse reactions did participants have during the study?
Who took part in the study?
The study included 265 participants at 68 research centers in 13 countries. The countries were Bulgaria, Canada, Czech Republic, Denmark, France, Germany, Hungary, Italy, Netherlands, Poland, Spain, Switzerland, and the United Kingdom.
The study included 145 (55%) men and 120 (45%) women. Participants were between 20 and 79 years old with an average age of 59.
Participants took part in this study if they:
Were 18 years of age or older
Had SFN for between 6 months and 10 years
Had SFN that was due to either diabetes or an unknown cause
For more information on who could take part in this study, please refer to the websites listed at the end of the summary.
What happened during the study?
The study started in May 2018 and ended in April 2021. There were 265 people who participated in the study.
How was the study done?
This was a Phase 2 study in which researchers tested a drug in a relatively small number of participants. It consisted of 2 parts, an open-label period and a double-blind period. During the open-label period, both the researchers and participants knew that all participants were receiving vixotrigine. During the double-blind period, none of the participants, doctors, or other study staff knew if a participant received vixotrigine or placebo.
The double-blind period was placebo-controlled. This means some participants received vixotrigine and some received placebo.
A placebo looks like the study drug but contains no real medicine. Using a placebo helps researchers make sure the effects they found in the study were actually caused by vixotrigine.
At the beginning of the study, all participants had an exam to make sure they could join the study. This included a physical exam and blood and urine tests. They also answered questions about their medical history.
Participants were asked to record their symptoms. Every evening, they rated the average amount of pain they felt in the past 24 hours on a scale of 0 (no pain) to 10 (worst pain). Researchers used these scores to find out if vixotrigine was working.
Before starting the open-label period, participants went through tapering and a washout of any pain drugs they were taking for SFN. Tapering means a gradual lowering of a dose until you stop taking a drug. Washout is the period of time after stopping a drug before starting a new one. This is done to be sure all of the first drug is out of the body.
During the open-label period, all participants were treated with vixotrigine for 4 weeks. They took 350 milligrams (mg) of vixotrigine as tablets by mouth 2 times a day.
There were 265 participants who took part in the open-label period.
Researchers considered a participant to be responding to vixotrigine if their daily pain score improved by at least 30% - about one-third better. Participants whose pain got better could take part in the double-blind period.
During the double-blind period, participants were randomly placed in 1 of 3 groups. Of the 265 participants who entered the open-label period, 122 took part in the double-blind period. Participants took either vixotrigine or placebo 2 times a day for another 12 weeks.
The doses and number of participants for each group in the double-blind period are shown below.
Double-blind period:
Placebo – 41 participants
Vixotrigine 200 mg – 40 participants
Vixotrigine 350 mg – 41 participants
On March 8, 2021, Biogen decided to end the study early.
What were the study results?
When the study ended, Biogen reviewed the data and created a report of the results. This is a summary of that report. Below is an overall summary of the results and the key questions researchers asked during the study.
Did taking vixotrigine lower the amount of SFN pain felt by participants after being in the study for about 16 weeks?
To answer this question, researchers looked at the daily pain scores that participants recorded in their diaries. They compared the scores from 5 days before starting the open-label period to the scores from the last week of receiving vixotrigine. Researchers calculated the change in daily pain scores for each group that was in the double-blind period.
One participant in the placebo group left the study early and is not included in the results.
The list below shows how much each group’s average pain scores changed after 16 weeks.
Placebo
Decrease in average pain score: 3.1
Vixotrigine 200 mg
Decrease in average pain score: 4.0
Vixotrigine 300 mg
Decrease in average pain score: 3.3
Participants who took vixotrigine 200 mg reported that their pain score was lower than participants in the placebo group. Researchers calculated and determined that this difference was significant. There was a small difference between the vixotrigine 350 mg group and the placebo group. Researchers calculated and determined that this difference was not significant.
What adverse reactions happened during the study?This section is a summary of the adverse reactions the participants had during the study. An adverse reaction is a new medical problem that a participant experiences during the study that is believed to be caused by the study drug. A lot of research is needed to know whether a study drug causes an adverse reaction. An adverse reaction is considered serious when it results in death, is life-threatening, causes lasting problems, or requires hospital care. When new drugs are being studied, researchers keep track of all adverse reactions that happen to participants during a study. Not everyone experiences the same adverse reactions.
Did any adverse reactions happen during this study?
A summary of the adverse reactions that happened during the open-label period is shown below.
Vixotrigine 350 mg – 265 participants
77 participants (29%) had adverse reactions.
1 participant (under 1%) had a serious adverse reaction.
11 participants (4%) stopped treatment because of an adverse reaction.No participants died due to an adverse reaction.
A summary of the adverse reactions that happened during the double-blind period is shown below.
Placebo – 41 participants
7 participants (17%) had adverse reactions.
No participants had any serious adverse reactions.
No participants stopped treatment because of an adverse reaction.No participants died due to an adverse reaction.
Vixotrigine 200 mg – 40 participants
3 participants (8%) had adverse reactions.
No participants had any serious adverse reactions.
1 participant (3%) stopped treatment because of an adverse reaction.No participants died due to an adverse reaction.
Vixotrigine 350 mg – 41 participants
8 participants (20%) had adverse reactions.
No participants had any serious adverse reactions.
No participants stopped treatment because of an adverse reaction.No participants died due to an adverse reaction.
What serious adverse reactions happened during the study?
The serious adverse reactions that happened to participants during the open-label period are listed below.
Vixotrigine 350 mg – 265 participants
1 participant (less than 1%) had a rash.
No participants experienced any serious adverse reactions during the double-blind period.
What common adverse reactions happened during the study?
The most common adverse reactions that happened in at least 2% of participants during the open-label period are listed below.
Vixotrigine 350 mg – 265 participants
24 participants (9%) had dizziness.
16 participants (6%) had headaches.
10 participants (4%) had a spinning sensation.
8 participants (3%) had nausea.
6 participants (2%) had sleepiness.
There was only 1 adverse reaction that happened in more than 1 participant during the double-blind period.
Placebo – 41 participants
3 participants (7%) had headaches.
Vixotrigine 200 mg – 40 participants
No participants had headaches.
Vixotrigine 350 mg – 41 participants1 participant (2%) had headaches.
How has this study helped patients and researchers?
This study showed that vixotrigine may potentially lower the amount of pain felt by participants with SFN. The group that received 200 mg of vixotrigine had, on average, significantly lower pain scores than the group that received placebo. The study also helped researchers learn more about the safety of vixotrigine in participants with SFN.
Where can I learn more about the study?
You can find more information about the study online at https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrials.gov%2F&data=05%7C01%7Capprovals%40hra.nhs.uk%7C4d13bbd4289c49add8f208dadcfeba48%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638065283845773312%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=wH8CYVv1d15yYonUrUGLJcmhNz2CApJCs%2BUrbSFGqQU%3D&reserved=0. Once on the site, type NCT03339336 into the search box and click “Search”.
You can also find more information online at https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrialsregister.eu%2F&data=05%7C01%7Capprovals%40hra.nhs.uk%7C4d13bbd4289c49add8f208dadcfeba48%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638065283845773312%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=ReECVYBIPJjeye5%2F3Dg6u8d83nBS%2Fw59jZ8U94R1VO8%3D&reserved=0. Once on the site, click “Home & Search,” then type: 2017-000991-27 in the search box and click “Search”.
If you have questions about vixotrigine (BIIB074) or the results of this study, please speak with the doctor or staff at the study research center.
Official study title: A Phase 2 Placebo-Controlled, Double-Blind, Enriched Enrollment Randomized Withdrawal Study to Evaluate the Efficacy and Safety of BIIB074 (Vixotrigine) in Treating Pain Experienced by Subjects With Confirmed Small Fiber Neuropathy That is Idiopathic or Associated With Diabetes Mellitus
Biogen, the sponsor of this study, has its headquarters in Cambridge, Massachusetts (USA).
The results presented here are for a single study. You should not make changes to your therapy based on these results without first consulting your doctor.REC name
Wales REC 3
REC reference
18/WA/0001
Date of REC Opinion
27 Feb 2018
REC opinion
Further Information Favourable Opinion