Safety and Tolerability of Intravitreal Administration of VG901 in Patients With Retinitis Pigmentosa Due to Mutations in the CNGA1 Gene

Launched by VIGENERON GMBH · Feb 26, 2024

Keywords

ClinConnect Summary

This clinical trial is looking at a new gene therapy called VG901 to see if it is safe and effective for people with a rare eye condition called Retinitis Pigmentosa (RP), specifically those with changes in a gene known as CNGA1. The main goals of the study are to find out the best dose of the treatment that patients can tolerate and to check for any side effects, especially any inflammation after receiving the therapy. Participants will receive a single injection of VG901 directly into the eye that is most affected by the condition and will be monitored for one year to see how well it works.

To join the trial, participants must be at least 18 years old, have a confirmed diagnosis of Retinitis Pigmentosa, and have specific genetic changes in the CNGA1 gene. They also need to have enough remaining vision in one eye to be eligible. The study is currently recruiting participants of all genders. If you decide to participate, you will receive the treatment and have regular follow-ups to monitor your health and any changes in your vision. This trial is an important step towards understanding how gene therapy might help those affected by this condition.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• To be eligible for study entry, subjects must satisfy all the following criteria:
• • 1. Able to understand and willing to consent to study participation by a written informed consent
• • 2. Male or female ≥ 18 years of age
• • 3. Clinical diagnosis of RP
• • 4. Confirmed pathogenic, biallelic variants in the CNGA1 gene
• • 5. Ellipsoid zone (EZ) length of the fovea of ≥ 3000 μm in the study eye
• Exclusion Criteria:
• Subjects will be excluded from the study if one or more of the following statements are applicable to either eye:
• • 1. Additional interfering ocular conditions which would impact study results (e.g., ocular opacity and advanced cataract, uveitis, amblyopia)
• • 2. History or presence of glaucoma
• • 3. Ocular surgery, intravitreal or subretinal implantation of a medical device (within 6 months of screening)
• • 4. Mutations known to cause inherited retinal disease other than biallelic variants in the CNGA1 gene
• • 5. History of ocular infection with herpes simplex virus
• • 6. History of ocular malignancies
• • 7. History of disorders of the internal retina (e.g., retinal detachment)
• • 8. Patients with uncontrolled diabetes (HbA1c \> 7%)
• • 9. Any other retinopathy due to other diseases - including, but not limited to arterial hypertension, previous vascular retinal occlusion, trauma or acquired inflammatory diseases, contraindication to pharmacological mydriasis (e.g., history of angle block glaucoma), diabetes (diabetic retinopathy including macular oedema)
• • 10. Absence of visual function on the contralateral eye
• • 11. Any damage to the optic nerve
• • 12. Individuals performing any other therapy for RP within 3 months before the study, such as - but not limited to - transcorneal electrostimulation
• • 13. Systemic conditions (e.g., autoimmune disorders) which may affect study participation or outcome measures
• • 14. History of immunodeficiency or other medical conditions which may increase the risk of VG901 administration
• • 15. Systemic illness (e.g., hepatitis or human immunodeficiency virus \[HIV\] infection) or medically relevant abnormal laboratory values (3 x upper limit of normal \[ULN\]) in blood analysis including renal and hepatic function
• • 16. Current, or recent, participation in other study/ or administration of investigational biologic agent within 3 months of Screening; Use of any investigational agent, or systemic corticosteroids, or other immunosuppressive drug(s) within 3 months before Screening
• • 17. History of allergy or sensitivity to any compound used in the study
• • 18. Contraindications to systemic immunosuppression
• • 19. Subjects with increased risk of bleeding (i.e., use of anticoagulants or anti-platelet agents within 7 days before VG901 administration and subjects with international normalized ratio \> 2 or Quick \< 50% or partial thromboplastin time \> 50 seconds, thrombocytopenia, as well as any other known coagulopathy)
• • 20. Subject/partner of childbearing potential unwilling to use adequate contraception for the period between Screening and 30 days after treatment, defined as the period from Screening until 30 days after treatment (defined as administration of therapeutic to the eye)
• • 21. For females of childbearing potential, a positive pregnancy test at Screening or Baseline
• • 22. Females who are breastfeeding
• • 23. Previous receipt of any AAV gene therapy product
• • 24. Any condition which leads the investigator to believe that subject cannot comply with the protocol requirements or that may place the subject at an unacceptable risk from participating