STAR Study
Research type
Research Study
Full title
A Single-Masked, Randomised, Controlled, Parallel Group, Phase 3 Clinical Trial Of Retinal Gene Therapy For Choroideremia Using An Adeno-Associated Viral Vector (AAV2) Encoding Rab Escort Protein 1 (REP1)
IRAS ID
193561
Contact name
Robert MacLaren
Contact email
Sponsor organisation
NightstaRx Ltd
Eudract number
2015-003958-41
Duration of Study in the UK
1 years, 6 months, days
Research summary
Research Summary
Choroideremia (CHM) is an incurable genetic disease that causes blindness. The disease is caused by a defect in a certain gene located on the X-chromosome, and this is why the disease affects men and women differently.
In CHM, this faulty gene results in a progressive degeneration of the retina (the light sensitive part of the eye responsible for vision, which is like a camera film that lines the back of the eye). Sight loss in CHM begins with “night blindness” (ie, a loss of night vision) in adolescence, followed by a gradual loss of peripheral vision which results in progressively worsening “tunnel vision”. Ultimately, central vision is lost by the fourth or fifth decade.
There are currently no effective treatments available for CHM. This clinical trial will investigate whether a gene therapy (a technique that involves putting normal copies of the faulty gene back into the cells of the retina) may help the cells in the retina affected by this disease, to function normally. The gene therapy consists of a virus which has been disabled so that it cannot cause infection. This virus has been specially altered to carry the normal genes into the cells in the retina. The altered virus is delivered to the retina during an operation where it will produce multiple copies of the normal gene.
The purpose of this study is to find out if vision in patients suffering from CHM can be preserved by replacing the defective gene using an experimental (not available on the UK market) gene therapy called Adeno-Associated Viral Vector (AAV2) Encoding Rab Escort Protein (REP-1), ie AAV2-REP1 in subjects with CHM and to evaluate the efficacy and safety of a single sub-retinal injection of AAV2-REP1.Summary of Results
Research Sponsor: Biogen Drug Studied: BIIB111 Protocol Number: 273CH301 (NSR-REP-01) Study Dates:
Study Start Date: December 11, 2017
Study Completion Date: December 1, 2020 Short Study Title: Clinical Trial of an Investigational New Gene Therapy for ChoroideremiaThank you!
Thank you to the participants who took part in the study of an investigational gene therapy drug, known as BIIB111. All the participants helped the researchers learn more about BIIB111 in people with choroideremia. Choroideremia is a rare genetic condition that leads to vision problems and eventually leads to blindness.NightstaRx Ltd, a Biogen Company, sponsored this study and reviewed the results when this study ended. Biogen thinks it is important to share the results with the participants and the public.
We hope this helps the participants understand and feel proud of their important role in medical research. If you have questions, please speak with the doctor or staff at the study site. What was the purpose of this study?
Researchers are looking for a treatment to help people with choroideremia. They wanted to learn about the use of BIIB111 as a gene therapy in male participants with choroideremia. In this study, the gene therapy replaced a non-working copy of the CHM gene with a working copy of the CHM gene in the retina.
Choroideremia is a rare eye condition that begins in childhood and eventually leads to blindness by middle age. It most commonly affects males. Choroideremia is caused by a defect in the CHM gene located on the X-chromosome.
Most participants living with choroideremia become blind by their 40s after gradual vision loss, which occurs over many years. There are no current treatments for choroideremia.
Researchers wanted to find out if replacing the non-working copy of the CHM gene with a working copy of the gene could help improve the vision of participants living with choroideremia.
The main question that the researchers wanted to answer was:
• How many participants had an improvement in sharpness of vision 1 year after receiving BIIB111?Who took part in the study?
The study included 164 participants either received BIIB111 or had at least 1 study site visit or call. All participants were between 18 to 79 years old.
The study took place at 18 research centers in Canada, Denmark, Finland, France, Great Britain, Germany, the Netherlands, and the United States.
Participants took part in this study if they:
• Were male
• Had choroideremia due to defect in CHM gene
• Were or above 18 years of ageWhat happened during the study?
The study started in December 2017 and ended in December 2020. There were 164 people who participated in the study. These 164 participants either received BIIB111 or had at least 1 study site visit or call with study site staff. Participants had to have choroideremia due to a defect in their CHM gene. They answered questions about their medical history before the study began. When the study ended, the sponsor created a report of the results. This is a summary of that report.
How was the study done?
This was an open label, dose blinded, randomized, Phase 3 study. Open label means that the participants, study staff, and researchers knew who received BIIB111 and who did not. Dose blinded means that participants and researchers did not know who received a high or low dose of BIIB111. Randomized means that a computer program randomly chose the treatment for each participant.
The participants were randomly placed into 1 of 3 different treatment groups.
• 65 participants received No Treatment in either eye
• 34 participants received BIIB111 Low Dose in study eye
• 65 participants received BIIB111 High Dose in study eyeFor all participants, one eye for each participant was chosen by the investigator as the study eye before participants were placed into one of the treatment groups. The study eye was typically the eye with the worse vision or suitable for surgery. The other eye that did not receive treatment was called the fellow eye.
Participants in BIIB111 Low Dose and BIIB111 High Dose groups received a single dose of BIIB111. BIIB111 was injected under the retina of the study eye.Participants in the No Treatment group did not undergo surgery or receive BIIB111 in either of their eyes.
All participants who received BIIB111 visited the study site 8 times over a 12-month period. The No Treatment group visited the study site 5 times and was contacted by phone call 3 times over a 12-month period. During these study site visits, participants took part in vision tests and study doctors and staff checked participants for any medical problems. During the phone calls, study doctors and staff checked participants for any medical problem.
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What were the study results?When the study ended, the sponsor 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.
The results include 161 participants. Out of 164, 3 participants did not have vision tests, so they are not included in the study results.
How many participants had an improvement in sharpness of vision, also called visual acuity, 1 year after receiving BIIB111?
Visual acuity is a measurement of how clearly participants can see. The vision exam used in the study was the Best-Corrected Visual Acuity Test. Researchers had participants read letters at a distance of 4 meters (about 13 feet) from the chart. If participants could not read the chart at this distance, they then tried to read it at 1 meter (about 3 feet). Each participant took the test for the study eye and the fellow eye.
For this study, a participant’s visual acuity was considered improved if they could read at least 15 more letters 1 year after joining the study.
The results of total number of participants, numbers of participants’ visual acuity were considered improved with the percent for both study eye and fellow eye within each group are given below.
No Treatment Group – 62 participants
Study eye – 0 participants
Fellow eye – 0 participantsBIIB111 Low Dose – 34 participants
Study eye – 1 participant (3%)
Fellow eye – 0 participantsBIIB111 High Dose – 65 participants
Study eye – 3 participants (5%)
Fellow eye – 2 participants (3%)Based on the results, researchers believe that any differences in visual acuity the BIIB111 groups and the No Treatment group were not significant rather than because of BIIB111.
What adverse reactions happened during the study?
This section is a summary of the adverse reactions the participants had during the study. 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 participants have during the study that they believe were caused by the study drug. Not everyone experiences the same adverse reactions.
This section includes adverse reactions for 164 participants. This includes participants who received BIIB111 and had at least 1 clinical visit or phone call with study staff. For the group that did not receive treatment, participants are included in the results if they had at least 1 call with the study staff.
One goal of this study was to learn more about the potential adverse reactions of BIIB111.
Did any adverse reactions happen during this study?
The summary of adverse reactions for each group is shown below which includes the total number of participants, number of participants who had either adverse reactions or serious adverse reaction with the percent in each group.
No Treatment Group – 65 participants
There were no adverse reaction or serious adverse reactions in this group.BIIB111 Low Dose Group – 34 participants
3 participants (9%) had adverse reactions.
2 participants (6%) had serious adverse reactions.BIIB111 High Dose Group – 65 participants
5 participants (8%) had adverse reactions.
2 participants (3%) had serious adverse reactions.No participants died in this study from adverse reactions or any other health problems.
What serious adverse reactions happened during the study?
The serious adverse reactions that happened during the study are shown below.
No Treatment Group – 65 participants
There were no adverse reactions in this group.BIIB111 Low Dose Group – 34 participants
2 participants (6%) had a reduction in visual acuity.BIIB111 High Dose Group – 65 participants
1 participant (2%) had a reduction in visual acuity.
1 participant (2%) had impaired vision.What common adverse reactions happened during the study?
The common adverse reactions that happened during the study are shown below.
No Treatment Group – 65 participants
There were no serious adverse reactions in this group.BIIB111 Low Dose Group – 34 participants
2 participants (6%) had a reduction in visual acuity.
1 participant (3%) had presence of cells in the back of the eye.BIIB111 High Dose Group – 65 participants
1 participant (2%) had a reduction in visual acuity.
1 participant (2%) had vision loss.
1 participant (2%) had presence of cells in the back of the eye.
1 participant (2%) had inflammation of middle cavity of the eye.
1 participant (2%) had increased pressure in the eyeHow has this study helped patients and researchers?
This study helped researchers learn more about possible ways to treat choroideremia.
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=04%7C01%7Capprovals%40hra.nhs.uk%7Ccd6edfa2227b4a30a2d208d9e4e73683%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637792504016068134%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=kjQm8UfMIz%2F8IKqRicgeT8bk4vD%2FB%2BAu44STI8CoCGw%3D&reserved=0. Once on the site, type NCT03496012 into the search box and click “Search”.You can also find more information online at Clinical Trials Register. Once on the site, click “Home & Search,” then type: 2015-003958-41 in the search box and click “Search”.
If you have questions about the BIIB111 or the results of this study, please speak with the doctor or staff at the study research center.
Official study title: A Randomized, Open Label, Outcomes-Assessor Masked, Prospective, Parallel Controlled Group, Phase 3 Clinical Trial of Retinal Gene Therapy for Choroideremia Using an Adeno-Associated Viral Vector (AAV2) Encoding Rab Escort Protein 1 (REP1)
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.
Thank you.
Biogen
225 Binney Street
Cambridge, MA 02142
USA
ClinicalTrials@Biogen.comREC name
London - West London & GTAC Research Ethics Committee
REC reference
16/LO/0086
Date of REC Opinion
29 Mar 2016
REC opinion
Further Information Favourable Opinion