Study of the Progression of Choroideremia, V1, 23Mar2015

• Research type

  Research Study

• Full title

  Natural History of the Progression of Choroideremia (NIGHT).

• IRAS ID

  178217

• Contact name

  Graeme Black

• Contact email

  graeme.black@manchester.ac.uk

• Sponsor organisation

  NightstaRx Limited

• Duration of Study in the UK

  1 years, 0 months, 0 days

• Research summary

  Research Summary
  Choroideremia (CHM) is a rare, X-linked recessive, degenerative disease of the retina characterized by progressive chorioretinal degeneration with early retinal thickening, followed by photoreceptor degeneration, retinal pigment epithelium (RPE) depigmentation and retinal remodeling. It begins in childhood with loss of night vision and gradually progresses to legal blindness by the fifth decade. CHM has a prevalence of approximately 1:50,000 and males are primarily affected over females. CHM is caused by null mutations in the CHM gene which encodes component A of Rab escort protein 1 (REP 1). REP1 function is essential for the normal function of photoreceptors and the RPE, and deficiency in REP1 results in disruption of intracellular transport and premature cell death. Thus, loss of REP1 function in the retina causes the progressive vision loss and blindness associated with CHM.

  CHM-related blinded is extremely debilitating and causes significant morbidity with economic, psychological, emotional and social implications. CHM is incurable and treatment is supportive at best. A significant unmet need exists for new and effective therapies for this blinding disease, especially those designed to halt or significantly reduce the rate of progression.

  For any intervention to receive regulatory approval for treatment, a clinically meaningful effect of the intervention must be demonstrated through adequate, well-controlled studies. Rational, scientifically-based drug development requires an understanding of the disease under study, including knowledge of its natural history. Rare diseases such as CHM are often poorly characterized due to the scarcity of data available from a limited patient population. Thus, drug development aimed at treating CHM is hampered by insufficient knowledge of the natural history of the disease. The study described aims to provide this knowledge.

  Summary of Results
  Thank you to the participants who took part in the study. All the participants helped the researchers learn more about people with choroideremia. Choroideremia is a rare genetic condition that causes vision problems and eventually 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 information 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 trying to learn more about choroideremia and how it develops over time. 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 drugs for choroideremia. As a result, there is an unmet need for new drugs to help people with this condition.

  Before researchers can develop a new drug, they need to understand the disease they want to treat. They need to better understand how the disease affects people and how it changes over time. This helps researchers find ways new drugs can work.

  There were no drugs given to participants in this study. Instead, researchers observed participants and kept track of changes to their vision and overall health. This kind of information will help researchers create better clinical trials for drugs to treat choroideremia. Researchers were especially interested in observing changes to visual acuity over time. Visual acuity is a measurement of how clearly a person can see.

  The main question that the researchers wanted to answer was:
  • How did participants’ visual acuity change over 20 months?

  Who took part in the study?
  The study included 318 participants. All participants were between 18 and 76 years old.

  The study took place at 19 research centers in Brazil, Canada, Denmark, Finland, France, Germany, the Netherlands, the United Kingdom, and the United States.

  Participants took part in this study if they:
  • Were male
  • Were 18 years of age or older
  • Had choroideremia due to defect in CHM gene

  What happened during the study?
  The study started in June 2015 and ended in October 2020. There were 318 people who participated in the study. 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 observational study which means no drugs were given to participants. Instead, researchers observed participants over the course of 20 months. Participants visited the study site 6 times during this period. Each visit was 4 months apart.

  During each visit, participants’ visual acuity was checked. 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 separately for each of their eyes. The result of the test is the total number of letters correctly read by the participant.

  After Visit 1, participants were split into 3 groups based on the number of letters they could read in the visual acuity test. Since each eye had its own score, the lower score between the two eyes was used.

  • Group 1: 74 letters or more (50 participants)
  • Group 2: between 34 and 74 letters (208 participants)
  • Group 3: fewer than 34 letters (60 participants)

  Participants also had full eye exams and other vision tests done during each visit. Researchers recorded any medical problems and symptoms that participants felt. Some participants had 2 additional visits to further check their visual acuity.

  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.

  Participants were allowed to leave the study at any time. Only 207 remaining participants took the visual acuity test at Month 20.

  How did participants’ visual acuity change over 20 months?
  Researchers found that participants’ visual acuity mostly remained stable over the course of 20 months. The average number of letters they could read did not change by much. Participants in Group 3 had the greatest change in visual acuity for both eyes.

  The results for all groups are given below. Negative numbers mean fewer letters could be read after 20 months. Positive numbers mean more letters could be read. The average change in the number of letters read is shown for each eye separately.

  Group 1 – 50 participants
  Worse Eye: -0.6
  Better Eye: -1.4

  Group 2 – 208 participants
  Worse Eye: +0.4
  Better Eye: -0.6

  Group 3 – 60 participants
  Worse Eye: +1.7
  Better Eye: -2.0

  Overall (all participants)
  Worse Eye: +0.4
  Better Eye: -1.1

  What medical problems happened during the study?
  This section is a summary of the new medical problems the participants had during the study. A lot of research is needed to know if participating in a study causes a medical problem, also called an adverse event. An adverse event is considered “serious” when it results in death, is life-threatening, causes lasting problems, or requires hospital care. When a study is being conducted, researchers keep track of all adverse events that participants have during the study. Not everyone experiences the same adverse events.

  Did any serious adverse events happen during this study?
  A total of 10 participants had at least 1 serious adverse event unrelated to their eyes. Only 1 participant in Group 1 had a serious adverse event related to their eyes. The summary for each group is shown below.

  Group 1 – 50 participants
  2 participants (4%) had serious adverse events.
  Group 2 – 208 participants
  6 participants (3%) had serious adverse events.

  Group 3 – 60 participants
  3 participants (5%) had serious adverse events.

  There were 2 participants that died during the study. One participant in Group 2 died due to a stroke. Another participant in Group 2 died due to kidney failure.

  None of these adverse events or deaths were considered related to participation in the study.

  What serious adverse events happened during the study?
  The serious adverse events that happened during the study are shown below.

  Group 1 – 50 participants
  1 participant (2%) had a hole in part of their retina.
  1 participant (2%) had a bulging disc in their spine.

  Group 2 – 208 participants
  1 participant (under 1%) had a forearm fracture.
  1 participant (under 1%) had lung cancer and a stroke from a blood clot.
  1 participant (under 1%) had a lung infection due to COVID-19.
  1 participant (under 1%) had a kidney injury.
  1 participant (under 1%) had asthma.
  1 participant (under 1%) had deafness.

  Group 3 – 60 participants
  1 participant (2%) had belly pain and kidney stones.
  1 participant (2%) had a lung infection, a kidney infection, and bladder cancer.
  1 participant (2%) had a stroke.

  None of these adverse events were considered related to participation in the study.

  How has this study helped patients and researchers?
  This study helped researchers learn more about how choroideremia develops and how it affects vision and overall health. This kind of information will help researchers create better clinical trials for drugs 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%7C8d9d698b192041d2d10f08d9f12c6675%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637805995264547713%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=Q1ZVeZ4qNN0y3EA3KxI0LzGnk8efgoWmKdvRdBQryNc%3D&reserved=0. Once on the site, type NCT03359551 into the search box and click “Search”.

  If you have questions about the results of this study, please speak with the doctor or staff at the study research center.

  Official study title: Natural History of the Progression of Choroideremia Study

  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.com

• REC name

  West Midlands - Coventry & Warwickshire Research Ethics Committee

• REC reference

  15/WM/0156

• Date of REC Opinion

  28 Apr 2015

• REC opinion

  Further Information Favourable Opinion