These clinical trials and natural history studies have the potential to benefit people with Usher syndrome.
Each research project listed below will include a graphic of the research continuum. The gold box indicates where this project falls on the continuum, illustrating its progress towards reaching people living with Usher syndrome, from "Bench to Bedside."
Stem Cell Therapy Clinical Trials
Clinical Trial for Safety and Tolerability of hRPC in Retinitis Pigmentosa (hRPCRP)
ReNeuron is a UK-based stem cell research company that focuses on developing stem cell therapies that target areas of "significant unmet or poorly met medical need." They have used their stem cell technologies to develop cell-based therapies for significant diseases where cells can be readily administered to any eligible patient without the need for additional drug treatment. Currently, they are developing the human retinal progenitor cell line (hRPC) for the treatment of retinal diseases such as retinitis pigmentosa (RP).
ReNeuron’s hRPC therapeutic candidate is undergoing Phase 2a clinical evaluations for the treatment of retinitis pigmentosa (‘RP’), which affects 1 in 4,000 people in the US and worldwide. The expanded study encompasses four sites worldwide, with two sites in the US as well as the recently activated sites in the UK and in Spain. The study uses a cryopreserved human retinal progenitor cell line (‘hRPC’) formulation, enrolling subjects with advanced RP with some remaining central vision. The 2 million cell dose used in this study extension represents a doubling of the earlier dose level, where good product safety and efficacy signals were seen in subjects followed out to 12 months. As previously announced, the Company expects to present early efficacy data from the extension segment of the Phase 2a study in Q1 2022. ReNeuron remains on track for advancing the programme into the next clinical trial by the end of 2022.
- First subject treated at Oxford Eye Hospital in Phase 2a RP trial (October 18, 2021)
- Positive Preliminary Data: Significant improvement in vision in first cohort of Phase II subjects in US trial of hRPC cell therapy in retinitis pigmentosa (February 20, 2019)
- ReNeuron Website
- Additional Information on hRPCs for Retinal Diseases
- ClinicalTrials.gov listing: Safety and Tolerability of hRPC in Retinitis Pigmentosa (hRPCRP)
Clinical Trial for Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
jCyte was founded in 2012 by Drs. Henry Klassen and Jing Yang, who have spent decades investigating the mechanisms that drive retinitis pigmentosa (RP) and other retinal diseases. Their work led to the creation of retinal progenitor cells (RPCs), a type of stem cell that can only become retinal cells. Clinical studies have shown that these cells could rescue and even replace diseased retinal cells. Early results from a phase 1/2a study have shown the treatment is safe and does not trigger an immune response. They have completed the enrollment and recruitment for their current phase 2b trial.
- jCyte Website
- Additional Information on jCells
- ClinicalTrials.gov listing for Phase 1/2a Study
- ClinicalTrials.gov listing for Phase 2b Study
Cedars-Sinai, a non-profit healthcare organization based in Los Angeles, has received authorizations from the FDA to launch a 16-person, Phase 1/2a clinical trial of human neural progenitor cells--stem cells that have almost developed into neural cells--for patients with RP. The trial is being funded by a $10.5 million grant from the California Institute for Regenerative Medicine. The study's principal investigator is Clive Svendsen, PhD, professor of Biomedical Sciences and Medicine and director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute.
Gene Therapy Based Clinical Trials
ProQR's Stellar Clinical Trial
March 2021 Update: ProQR has published positive results from its Phase 1/2 Stellar trial of QR-421a, an investigational RNA therapy for the treatment of Usher syndrome and retinitis pigmentosa (RP) due to mutation(s) in exon 13 of the USH2A gene. Stellar study, Phase 1/2 clinical trial showed investigational RNA therapy QR-421a is effective and safe. ProQR plans to start final phase trials for people with USH2A mediated retinitis pigmentosa. With only one injection of QR-421a, the Stellar study showed benefit in the treated eye in comparison to the untreated eye across multiple eye tests. This benefit was seen across all participants in the Stellar study, which included clinical trial participants with both advanced vision loss as well as early to moderate vision loss. Based on these positive results, ProQR plans to conduct two final stage clinical trials or Phase 2/3 trials. ProQR will work with regulators to submit clinical trial protocols for two final stage registration trials called Sirius and Celeste. For more information on the safety & efficacy of the Stellar trial, please read ProQR’s Community Statement, QR-421a program update March 2021.
STELLAR or PQ-421a-001, is a first-in-human study that will initially include approximately 18 adults with vision loss due to mutations in exon 13 of the USH2A gene and will be conducted at about seven expert sites in North America and Europe. QR-421a is designed to exclude exon 13 from the USH2A mRNA, thereby removing the mutation in exon 13. This approach is also known as exon skipping. RNA is the "blueprint" for protein synthesis, and the skipping of exon 13 in the "blueprint" is expected to lead to a shortened but functional Usherin protein.
- Link to Study Details on ClinicalTrials.gov
- View presentation on this study from the USH2019 Connections Conference
Safety and Efficacy of NPI-001 Tablets for RP Associated With Usher Syndrome (SLO RP)
Dr. Lee Anderson with sponsors and collaborators from Nacuity Pharmaceuticals Inc. and Foundation Fighting Blindness in Australia are looking at NPI-001 Tablets, an antioxidant drug. Their study will examine the safety and efficacy of these oral NPI-001 Tablets compared to placebo tablets for participants who have vision loss due to retinitis pigmentosa (RP) with Usher syndrome. The study takes place over the course of 24 months. This study is expected to be completed in September 2023.
Auditory Neural Function in Implanted Patients With Usher Syndrome
Dr. Shuman He with Ohio State University and the National Institute on Deafness and Other Communication Disorders (NIDCD) will be enrolling an estimated 44 participants starting in July 2021. Participants will have either Usher syndrome (USH) or idiopathic hearing loss. USH causes deterioration of the cochlear nerve (CN). This study hopes to create evidence-based therapies for cochlear implant patients with USH. The researchers' goals are to study neural health and how neurons represent temporal and spectral cues in implanted patients with USH. “Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.”
Nanoscope Therapeutics Receives Fast Track Designation by the FDA for MCO-010 for the Treatment of Retinitis Pigmentosa
Nanoscope Therapeutics Inc. is a clinical-stage biotechnology company that is developing gene-agnostic therapies for individuals with retinal degenerative diseases. In October 2022, the company announced the FDA has granted Fast Track Designation to their asset MCO-010, an optogenetic monotherapy, that through injection can be a treatment for retinitis pigmentosa (RP). MCO-010 is currently in a phase 2 clinical trial (NCT04945772) with results expected early 2023. Having a Fast Track Designation is significant because it expedites the review process of a novel therapy by allowing for increased communication with the FDA regarding regulatory hurdles.
Natural History Studies
Natural History Study In Subjects With USH1B
The natural history study is being conducted to understand the progression of the disease in patients with USH1B as measured by a number of vision-related assessments. Disease progression will be evaluated as change over time in these measures, and associations between endpoints will be examined. They are recruiting patients in Naples, Italy, in Madrid, Spain, and Rotterdam, Netherlands.
Locations and Principal Investigators:
Eye Clinic of the University of Campania Luigi Vanvitelli
Ingeborgh van den Born
Stichting Oogziekenhuis Rotterdam
DUAL AAV VECTOR FOR GENE THERAPY OF USH1B RETINITIS PIGMENTOSA ("USHTHER")
Alberto Auricchio, MD:
TIGEM Naples, Italy
A consortium of researchers around Alberto Aurrichio has worked on dual AAV vectors for non-clinical studies and a clinical trial. Currently the safety and expression of dual AAV vectors is being assessed in primates. Additionally, a phase 1/2 clinical trial to investigate the safety and efficacy of dual AAV-MYO7A vectors in humans has been designed.
The objective of the study USHTher is to test the safety and efficacy of an innovative gene therapy approach that uses dual AAV in retinas of USH1B patients. This study is the first time the dual AAV vector has been used in humans. Twelve USH1B patients will be given the dual AAV vectors for the study. The hope is that this study will create the basis for a cure for USH1B retinitis pigmentosa (RP). The use of dual AAV vectors could also hopefully be applied to other conditions that require large genes.
USH1C Natural History Study
Jennifer Lentz, Ph.D. and her team at the Neuroscience Center of Excellence, LSU--New Orleans are recruiting patients for three Natural History studies on Usher syndrome.
Studies being conducted by Dr. Lentz and her team include:
- Usher Syndrome in Louisiana Natural History Study
- Prospective Natural Study of Vision Loss in USH 1C: A Multicenter Study
- Prospective Natural History Study of the Loss of Balance in USH 1C
For more information about these special opportunities:
USH2A Natural History Study
According to Dr. Jacque Duncan, RUSH2A Study Chair, "Natural history studies are important to prepare investigators to design clinical trials. It's essential to know how vision is affected in patients with USH2A mutations in order to determine what to measure and how much change we expect to see over time, in order to know whether a potential treatment improves the vision or decreases the rate of vision loss in the long run."
Natural History Study of Usher Syndrome ( Light4Deaf )
Isabelle Audo Pr:
Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts
Researcher Isabelle Audo with sponsor Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts and collaborator Assistance Publique - Hôpitaux de Paris are currently doing a five-year natural history study of Usher Syndrome. This study aims to look at the functional and structural parameters for retinal, auditory and vestibular impairments that happen overtime. This will allow researchers to document the natural history of Usher syndrome and establish clinical endpoints that may be useful for future clinical trials.
Rate of Progression of PCDH15-Related Retinal Degeneration in Usher Syndrome 1F (RUSH1F)
The Usher 1F Collaborative, a family-founded nonprofit and the Foundation Fighting Blindness are partnering to launch a natural history study, “Rate of Progression of PCDH15-Related Retinal Degeneration in Usher Syndrome 1F (RUSH1F).” The Marjorie C. Adams Trust will provide additional funding for the study. This natural history study will follow 40 individuals with USH1F for four years. Its primary goal is to identify outcome measures in individuals with the PCDH15 mutation which causes USH1F. These outcome measures can be used in future clinical trials. The Jaeb Center for Health Research in Tampa Florida is the coordinating center. Dr. Katarina Stingl of the University of Tübingen in Germany will serve as the study chair. The study began enrolling participants in May 2021.
Uni-Rare Study, Natural History Study
Foundation Fighting Blindness (FFB) is a non-profit organization that funds research for treatment and cures for retinal diseases, including but not limited to Usher syndrome. In a recent press release, Foundation Fighting Blindness shared that they will be funding “$8.6 million for its Uni-Rare Study, a new natural history study for approximately 1,500 people with one of more than 300 rare genes associated with inherited retinal diseases (IRDs).”
For many inherited retinal diseases, there is still a lack of understanding of the retinal degeneration and disease progression. This natural history study aims to fill in the gaps to allow for a more comprehensive understanding of IRDs.
The Uni-Rare Study will prioritize genes that do not already have studies in progress and will consist of two parts. All participants will have an evaluation to collect genetic data and clinical data. Those who have mutations in the RDH12 (LCA) and MYO7A (USH1B) genes may qualify for the second part of the study where clinical data is collected for four additional years. Foundation Fighting Blindness asserts that “Additional gene cohorts for this part of the study are expected to be added in the future.”
Clinical Trials and Natural History Studies - Related Science News
In 2022, the Usher Syndrome Coalition partnered with ProQR to provide outreach and education for their clinical trial. That trial is now paused. Here are some steps you can take to make sure you're ready for future clinical trials.
Announcing our partnership with ProQR to support clinical trial enrollment for a potential therapy for USH2A mediated retinitis pigmentosa
ProQR has published positive results from its Phase 1/2 Stellar trial of QR-421a, an investigational RNA therapy for the treatment of Usher syndrome and retinitis pigmentosa (RP) due to mutation(s) in exon 13 of the USH2A gene.
ProQR Therapeutics announces positive findings from a planned three-month interim analysis of its Phase I/II Stellar trial of QR-421a to treat retinitis pigmentosa (RP) in adults who have Usher syndrome type 2 or non-syndromic RP due to mutations in a specific part of the USH2A gene, called exon 13. QR-421a, ProQR’s experimental RNA therapy is designed to skip exon 13 in the RNA with the aim to stop or reverse vision loss. QR-421a given as a single intravitreal injection was safe and well-tolerated. It also showed early and encouraging evidence of activity, with 25% of patients showing a benefit across multiple outcome measures.
What this means for Usher syndrome: While this particular experimental drug is only applicable to those with Usher syndrome due to mutation(s) in exon 13 of the USH2A gene, early positive findings mean that the trial will continue as designed and could lead to other RNA/drug therapies that will benefit people with Usher syndrome caused by other mutations.
Researchers from Sun Yat-sen University are attempting to test the efficacy and safety of oral minocycline for the treatment of retinitis pigmentosa (RP). Minocycline, a second generation, semi-synthetic tetracycline antibiotic, a highly lipophilic molecule and can easily pass through the blood-brain barrier. Several clinical trials and animal experiments have reported that minocycline exert anti-apoptotic, anti-inflammatory and antioxidant effects in treating neurodegenerative diseases. They have proposed to test the effect and safety of oral minocycline for RP.
What this means for Usher syndrome: If clinical trials are successful, Usher patients will have the possibility to be included in this non-invasive therapy to prevent photoreceptor cell death.
The identification of the causes and understandings of the functions of many inherited retinal diseases (IRDs) has led to the development of exciting new gene/disease specific treatment opportunities. There are numerous treatments available that are aimed at a level of not just targeting specific genes but also certain mutations. Therefore, gene/disease specific treatments rely on persistent target cells and sufficient visual function to work effectively. However, many patients are outside of this window of opportunity and must rely on other approaches.
What this means for Usher syndrome: there are many different treatment and therapy options that are in development for retinitis pigmentosa.
GenSight Biologics, a biopharma company focused on discovering and developing gene therapies for retinal neurodegenerative diseases and central nervous system disorders, announced that the independent Data Safety Monitoring Board (DSMB) has completed its first safety review of the ongoing PIONEER Phase I/II clinical trial of GS030 combining gene therapy and optogenetics for the treatment of Retinitis Pigmentosa (RP). No safety issues have been found for the first cohort of subjects who received a single intravitreal injection of 5e10 vg combined with a wearable optronic visual stimulation device. Therefore, the DSMB has recommended moving forward with the plan without any modification to the protocol and recruiting the second cohort of subjects to receive an escalated dose of 1.5e11 vg.
What this means for Usher syndrome: This clinical trial could lead to a treatment for RP and may be applicable to Usher syndrome.
ReNeuron Group plc has announced the latest updated positive preliminary results in the company’s ongoing phase 1 and 2a clinical trial of its human retinal progenitor cell (hRPC) therapy candidate in retinitis pigmentosa. All three subjects in the first group of phase 2a have demonstrated a sustained and further improvement in vision compared to their pre-treatment baseline.
What this means for Usher syndrome: This potential therapy could provide a means to restore lost vision in Usher syndrome patients.
ProQR Therapeutics N.V., a company dedicated to changing lives through the creation of transformative RNA medicines for the treatment of severe genetic rare diseases, today announced the first patient treated in the Phase 1/2 STELLAR clinical trial for QR-421a in patients with Usher syndrome type 2 or non-syndromic retinitis pigmentosa (RP). Interim data from the trial are expected to be announced by mid-2019. According to David G. Birch, Ph.D., Principal Investigator of STELLAR and Scientific Director of the Retina Foundation of the Southwest in Dallas, Texas, “The STELLAR study is one of the first studies of its kind exploring the impact of ProQR’s RNA therapies on patients with Usher syndrome type 2 due to an Exon 13 mutation. The STELLAR trial will explore whether QR-421a (ProQR’s RNA therapy) can slow disease progression or even reverse it.”
What this means for Usher syndrome: There may be a potential drug available to reverse blindness caused by Usher syndrome.
ProQR Therapeutics announced that the FDA has cleared the Investigational New Drug (IND) application for QR-421a. QR-421a is a first-in-class investigational RNA-based oligonucleotide designed to address the underlying cause of the vision loss associated with Usher syndrome type 2 and non-syndromic retinitis pigmentosa due to mutations in exon 13 of the USH2A gene. ProQR plans to start enrolling patients in a Phase 1/2 trial named STELLAR in the coming months with preliminary data expected in mid-2019.
ProQR Therapeutics N.V. announced the results for their clinical trial of QR-110 LCA 10 is on track, and eight out of twelve patients have been enrolled in a Phase 1/2 trial. The results for safety and efficacy for the trial are expected to be announced in the second half of 2018. Currently, they planing to announce data from a QR-421 study for Usher Syndrome. The organization has received $7.5 million in funding from the Foundation Fighting Blindness (FFB) and hopes to use QR-421a for Usher Syndrome Type 2A to target mutations in exon 13.
ReNeuron, a developer of cell-based therapeutics, received a $1.5 million grant award from the UK Innovations agency. The project will allow further development of cell banks of ReNeuron’s hRPC candidate and as well as the development of product release assays for late-stage clinical development. The hRPC therapy is currently being tested in a Phase III clinical trial in the US for patients suffering retinitis pigmentosa.
GenSight Biologics, a biopharma company focused on discovering and developing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders, announced UK Medicines and Healthcare Regulatory Agency (MHRA) acceptance of the Company’s Clinical Trial Application (CTA) to initiate the PIONEER Phase I/II study of GS030 in patients with Retinitis Pigmentosa (RP).
jCyte, one of the leaders in developing cell-based therapies for RP, announces positive 12-month results from its Phase 1/2a clinical trial to treat retinitis pigmentosa with stem cells.
Encouraging signs this week that the FDA is serious when it granted Regenerative Medicine Advanced Therapy (RMAT) status to the CIRM-funded jCyte clinical trial for a rare form of blindness. This is a big deal because RMAT seeks to accelerate approval for stem cell therapies that demonstrate they can help patients with unmet medical needs.
Our latest USH Talk features researcher Dr. Jacque Duncan from the University of California, San Francisco. Dr. Duncan shares an overview of an upcoming clinical trial that aims to study the rate of progression of USH2A related retinal degeneration: The RUSH2A Study.
Three patients have been treated so far with no serious adverse events after six months. They have been allowed to proceed to delivering a larger dose to the next group of patients.
The US Food and Drug Administration (FDA) has approved Oxford BioMedica's Investigational New Drug (IND) application for the Phase I/IIa clinical development of UshStat to treat Usher syndrome type 1B. Oxford Biometica will enroll 18 patients with Usher type 1b at the Casey Eye Institute in Portland, Oregon. The study will be lead by Dr. Richard Weleber.