Dose-Escalation Study to Evaluate the Safety and Tolerability of Intravitreal vMCO-I in Patients With Advanced Retinitis Pigmentosa

A Phase I/IIa Open Label, Dose-Escalation Study to Evaluate the Safety and Tolerability of Intravitreal vMCO-I in Patients With Advanced Retinitis Pigmentosa

The purpose of the study is to evaluate the safety and tolerability of a single intravitreal injection of virally-carried Multi-Characteristic Opsin I (vMCO-I)

Study Overview

• Status: Completed
• Conditions: Retinal Degeneration; Retinal Diseases; Retinitis Pigmentosa
• Intervention / Treatment: Biological: Gene Therapy product:vMCO-I

Detailed Description

This open label dose-escalation study evaluated 2 dose levels in up to 11 subjects of retinitis pigmentosa (3 in low dose and 8 in high dose per dose) with active vMCO-010. Subjects with confirmed diagnosis of Advanced Retinitis Pigmentosa (RP) based on clinical examination and dilated fundus examination, were considered for participation in this study. The primary endpoint for this study is safety and tolerability of vMCO-I at 16 weeks. All subjects were assessed for 52 weeks following treatment with vMCO-I

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• India
  • Odisha
    • Cuttack, Odisha, India, 753014
      • JPM Rotary Club of Cuttack Eye Hospital and Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age > 18 years
2. Diagnosis of advanced RP using Fundus Photographs
3. Clinical diagnosis of advanced retinal dystrophy
4. Prior documented (if any) retinal electrophysiological evidence of rod-cone photoreceptor degeneration
5. Snellen's visual acuity equivalent LP/NLP in worse (study) eye
6. Visual acuity in the non-study eye of no-better-than finger counting
7. Presence of retinal bipolar cells and retinal nerve fiber layer on OCT testing

Exclusion Criteria:

1. Prior participation in a clinical study (ocular or non-ocular) with an investigational drug, agent or therapy or any gene or stem cell therapy in the past six months.
2. Concurrent participation in another interventional clinical ocular study.
3. Pre-existing eye conditions such as glaucoma, diseases affecting the optic nerve causing significant visual field loss, active uveitis, corneal or lenticular opacities).
4. Presence of any complicating systemic diseases such as malignancies whose treatment could affect central nervous system function.
5. Subjects who are positive for hepatitis B, C, and HIV will be excluded.
6. Subjects who have undergone ocular surgery in the study eye within three months prior to Day 0.
7. Presence of narrow iridocorneal angles contraindicating pupillary dilation in the study eye.
8. Known sensitivity to any component of the study agent or medications planned for use in the peri-operative period.
9. Subjects will be excluded if immunological studies show presence of neutralizing antibodies to AAV2 above 1:1000.
10. Presence of narrow iridocorneal angles contraindicating pupillary dilation.
11. Presence of disorders of the ocular media which interfere with visual acuity and other ocular assessments, including OCT, during the study period.
12. Presence of vitreo-macular adhesion or traction, epiretinal membrane, macular pucker and macular hole, evident by ophthalmoscopy and/or by OCT examinations and assessed by the investigator to significantly affect central vision.
13. Current evidence of retinal detachment assessed by the investigator to significantly affect central vision.
14. Active ocular inflammation or recurrent history of idiopathic or autoimmune associated uveitis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: vMCO-I High dose; Participants received 3.5E11vg/eye of vMCO-I	Biological: Gene Therapy product:vMCO-I; The vMCO-I is an adeno-associated virus serotype 2-based vector carried multi-characteristic opsin (MCO) gene expression cassette
Experimental: vMCO-I Low Dose; Participants received 1.75E11vg/eye of vMCO-I	Biological: Gene Therapy product:vMCO-I; The vMCO-I is an adeno-associated virus serotype 2-based vector carried multi-characteristic opsin (MCO) gene expression cassette

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The safety and tolerability of escalating doses of vMCO-l administered via a single IVT in subjects with advanced Retinitis Pigmentosa	Safety and tolerability of vMCO-l treatment at Week 16, by assessments based on local and systemic safety issues, as assessed by incidence of Adverse Events.	16 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the treatment effect of vMCO-l as assessed by visual acuity	Assessment of the treatment effect with the change from baseline to Week 52 of parameters measured with the Freiburg Visual Acuity (FrACT) to provide automated, self-paced, monitored measurement	52 weeks
Evaluate the treatment effect of vMCO-l as assessed by Visually-guided Mobility assays	Assessment of the treatment effect with the change from baseline to Week 52 of parameters measured with Light-guided Mobility assays, performed at different light intensities, to provide functional vision measures using the time to find lighted panel	52 weeks
Evaluate the treatment effect of vMCO-l as assessed by Visually-guided Mobility assays	Assessment of the treatment effect with the change from baseline to Week 52 of parameters measured with Light-guided Mobility assays, performed at different light intensities, to provide functional vision measures using the score based on correct choice	52 weeks
Evaluate the treatment effect of vMCO-l as assessed by Static Shape recognition assay	Assessment of the treatment effect with the change from baseline to Week 52 of parameters measured with Static Shape recognition assay, performed at different light intensities, to provide visual function measures using size determination threshold	52 weeks
Evaluate the treatment effect of vMCO-l as assessed by Static Shape recognition assay	Assessment of the treatment effect with the change from baseline to Week 52 of parameters measured with Static Shape recognition assay, performed at different light intensities, to provide visual function measures using % shape recognition accuracy	52 weeks
Evaluate the treatment effect of vMCO-l as assessed by Optical Flow assay	Assessment of the treatment effect with the change from baseline to Week 52 of parameters measured with Optical Flow assay, performed at different speeds, to provide visual function measures using the %accuracy in determining direction of flow	52 weeks
Evaluate the treatment effect of vMCO-l as assessed by Optical Flow assay	Assessment of the treatment effect with the change from baseline to Week 52 of parameters measured with Optical Flow assay, performed at different speeds, to provide visual function measures using the Upper speed limit to determine correct optical flow	52 weeks
Evaluate the treatment effect of vMCO-l as assessed by Quality of Life Questionnaire	Assessment of the treatment effect on Quality of Life changes from baseline to Week 52 with Visual Function Questionnaire-25 (VFQ-25).VFQ25 is a 25-item questionnaire with 47 questions, each question has several responses scored on a scale from 0-5, 0-6, or 0-10. Values are calculated in percentages.	52 weeks
Evaluate the treatment effect of vMCO-l as assessed by Humphrey Visual Field	Assessment of the treatment effect with the change from baseline to Week 52 with Humphrey Visual Field (30-2). Visual Field Index (VFI) is calculated in % and Mean Deviation (MD) values are calculated in dB.	52 weeks

Collaborators and Investigators

• Sponsor: Nanoscope Therapeutics Inc.
• Investigators: Principal Investigator: Santosh Mahapatra, MD, JPM Rotary Club of Cuttack Eye Hospital and Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2019
• Primary Completion (Actual): February 25, 2020
• Study Completion (Actual): October 31, 2020

Study Registration Dates

• First Submitted: May 25, 2021
• First Submitted That Met QC Criteria: June 2, 2021
• First Posted (Actual): June 9, 2021

Study Record Updates

• Last Update Posted (Actual): June 9, 2021
• Last Update Submitted That Met QC Criteria: June 2, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Gene Therapy; Retinitis Pigmentosa; Retinal Degeneration; Optogenetics; AAV vectors; Multicharacteristic Opsin (MCO)-I
• Additional Relevant MeSH Terms: Eye Diseases; Genetic Diseases, Inborn; Eye Diseases, Hereditary; Retinal Dystrophies; Retinal Diseases; Retinitis; Retinitis Pigmentosa; Retinal Degeneration
• Other Study ID Numbers: NSCT/CT/18/01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The results of the clinical trial will be made available when the study is completed and results are analyzed. The results will be published on this site and be available to conference presentations and publications.
• IPD Sharing Time Frame: 6 months after the completion of the study
• IPD Sharing Access Criteria: IPD sharing access will be subject to data transfer agreement. IPD generated as part of this clinical study may be subject to patient confidentiality.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No