Nils Schärer

UniRare

Summary

The Registry will establish genetically and clinically well-characterized cohorts of patients across hundreds of genetic variants associated with retinal dystrophy (RD). Characterization of these patients will accelerate eligibility screening for the Natural History Study, provide cross-sectional data on phenotype-genotype associations, and contribute to our knowledge of pathogenicity of these rare disease-causing variants.

The Natural History Study will accelerate the identification and development of sensitive, reliable outcome measures for clinical trials, which will facilitate development of treatments for retinal dystrophies due to disease-causing genetic variants.

Design

There are two components of this international, multicenter study (approx. 40 sites):

Registry

• A standardized genetic screening and a prospective, standardized, cross-sectional clinical data collection

• Enrollment is open to all genes on the RD Rare Gene List

Natural History Study

• A prospective, standardized, longitudinal Natural History Study

• Enrollment opens gene-by-gene, based on funding and within-gene Registry enrollment

MGT-RPGR-022

Background

Retinitis pigmentosa (RP) is a group of inherited retinal diseases characterized by a progressive reduction in vision that first manifests as nyctalopia (night blindness) and usually occurs in childhood or early adulthood and progresses throughout life. Due to a number of X-linked forms, RP affects more males than females.

Currently, there is no approved therapeutic treatment for XLRP caused by mutations in RPGR (RPGR-XLRP). Among a number of new experimental strategies currently under investigation, gene therapy is considered the most promising.

This gene therapy study aims to determine whether a healthy version of the RPGR gene can correct this inherited error (defect) when delivered by injection into the retina during surgery.

Design

Approximately 90 adult subjects and up to 6 children and adolescents worldwide will participate in this study.

As part of this study, patients will be asked to give their consent to participate in 2 closely related studies. All participants must read the information about both studies and decide if they want to consent to participate. Initially, patients will participate in the first study (MGT-RPGR-021) for up to 18 months. Once patients have completed their participation in this study, they will proceed to the second study (MGT-RPGR-022), which has a follow-up period of 4 to 5 years.

The length of participation will depend on which treatment group the patient is assigned to in the study. It is necessary to have a group of non-treated participants to compare benefits and risks. Therefore, some participants will receive their treatment with a delay of 12 months. All participants will receive either the RPGR2e11 or RPGR4e11 dose of gene therapy tested in both eyes, either in the MGT-RPGR-021 study or 12 months later in the MGT-RPGR-022 study.

VELODROME

Background

Neovascular age-related macular degeneration (nAMD), is a form of advanced AMD that causes rapid and severe visual loss, and remains a leading cause of visual impairment in the elderly. It is suspected that a growth factor known as “vascular endothelial growth factor (VEGF)” plays a role in the development and leakage of abnormal blood vessels. These abnormal blood vessels allow blood or fluid to leak into the macula and form scars, which cause a deterioration of central vision.

Ranibizumab is a medication that works by blocking the growth factor VEGF to slow the growth of abnormal blood vessels in the eye and the leakage of blood or fluid from these vessels, thereby helping to prevent or slow vision loss.

A key challenge with currently available anti-VEGF treatments is the requirement for frequent and long-term administration.

The Port Delivery System (PDS) is a refillable eye implant device that releases ranibizumab into the eye continuously over time. The PDS can remain in the eye long-term unless removed for health reasons.

Design

In Switzerland, the plan is to enroll approximately 20 participants across a total of 5 study centers. Worldwide, approximately 450 participants are expected to take part in the study across roughly 120 study centers in about 16 countries. The study will last approximately 3 years.

The purpose of this study is to evaluate the positive and negative effects of ranibizumab delivered by the PDS, in people with nAMD. It will be refilled either every 6 months or 9 months. Everyone in this clinical trial will have the PDS with ranibizumab surgically inserted into one eye under anaesthetic.

PORTAL

Design

Extension study for the Port Delivery System (PDS) with ranibizumab. This study will evaluate the long-term safety and tolerability of the PDS with ranibizumab in participants with neovascular age-related macular degeneration (nAMD) who have either completed Phase II Study GX28228 (Ladder), Phase III Study GR40548 (Archway), Phase IIIb Study WR42221 (Velodrome), or completed Week 24 visit in Study WR42221 but were not eligible to be randomized in WR42221.

RUSH1F

Summary

This natural history study of patients with PCDH15 disease-causing variants will accelerate the development of outcome measures for clinical trials. Sensitive, reliable outcome measures of retinal degeneration will greatly facilitate development of treatments for retinitis pigmentosa due to PCDH15 disease-causing variants. Together these approaches are expected to have an impact on understanding PCDH15 related retinal degeneration, developing experimental treatment protocols, and assessing their effectiveness.

Design

Multicenter, longitudinal, prospective natural history study. Participants will be assigned to one of two Vision Cohorts based on visual acuity (VA) and kinetic visual fields (VF). Approx. 10 sites.