Back to resultsDose-Escalation Study to Evaluate the Safety and Tolerability of Intravitreal vMCO-I in Patients With Advanced Retinitis Pigmentosa
Primary Purpose
Retinitis Pigmentosa, Retinal Diseases, Retinal Degeneration
Status
Completed
Phase
Phase 1
Locations
India
Study Type
Interventional
Intervention
Gene Therapy product:vMCO-I
Sponsored by
About this trial
This is an interventional treatment trial for Retinitis Pigmentosa focused on measuring Retinitis Pigmentosa, Retinal Degeneration, Optogenetics, Gene Therapy, AAV vectors, Multicharacteristic Opsin (MCO)-I
Eligibility Criteria
Inclusion Criteria:
- Age > 18 years
- Diagnosis of advanced RP using Fundus Photographs
- Clinical diagnosis of advanced retinal dystrophy
- Prior documented (if any) retinal electrophysiological evidence of rod-cone photoreceptor degeneration
- Snellen's visual acuity equivalent LP/NLP in worse (study) eye
- Visual acuity in the non-study eye of no-better-than finger counting
- Presence of retinal bipolar cells and retinal nerve fiber layer on OCT testing
Exclusion Criteria:
- 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.
- Concurrent participation in another interventional clinical ocular study.
- Pre-existing eye conditions such as glaucoma, diseases affecting the optic nerve causing significant visual field loss, active uveitis, corneal or lenticular opacities).
- Presence of any complicating systemic diseases such as malignancies whose treatment could affect central nervous system function.
- Subjects who are positive for hepatitis B, C, and HIV will be excluded.
- Subjects who have undergone ocular surgery in the study eye within three months prior to Day 0.
- Presence of narrow iridocorneal angles contraindicating pupillary dilation in the study eye.
- Known sensitivity to any component of the study agent or medications planned for use in the peri-operative period.
- Subjects will be excluded if immunological studies show presence of neutralizing antibodies to AAV2 above 1:1000.
- Presence of narrow iridocorneal angles contraindicating pupillary dilation.
- Presence of disorders of the ocular media which interfere with visual acuity and other ocular assessments, including OCT, during the study period.
- 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.
- Current evidence of retinal detachment assessed by the investigator to significantly affect central vision.
- Active ocular inflammation or recurrent history of idiopathic or autoimmune associated uveitis.
Sites / Locations
- JPM Rotary Club of Cuttack Eye Hospital and Research Institute
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
vMCO-I High dose
vMCO-I Low Dose
Arm Description
Participants received 3.5E11vg/eye of vMCO-I
Participants received 1.75E11vg/eye of vMCO-I
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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
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
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
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
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
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
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
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04919473
Brief Title
Dose-Escalation Study to Evaluate the Safety and Tolerability of Intravitreal vMCO-I in Patients With Advanced Retinitis Pigmentosa
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
October 23, 2019 (Actual)
Primary Completion Date
February 25, 2020 (Actual)
Study Completion Date
October 31, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nanoscope Therapeutics Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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)
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Retinitis Pigmentosa, Retinal Diseases, Retinal Degeneration
Keywords
Retinitis Pigmentosa, Retinal Degeneration, Optogenetics, Gene Therapy, AAV vectors, Multicharacteristic Opsin (MCO)-I
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
11 (Actual)
8. Arms, Groups, and Interventions
Arm Title
vMCO-I High dose
Arm Type
Experimental
Arm Description
Participants received 3.5E11vg/eye of vMCO-I
Arm Title
vMCO-I Low Dose
Arm Type
Experimental
Arm Description
Participants received 1.75E11vg/eye of vMCO-I
Intervention Type
Biological
Intervention Name(s)
Gene Therapy product:vMCO-I
Intervention Description
The vMCO-I is an adeno-associated virus serotype 2-based vector carried multi-characteristic opsin (MCO) gene expression cassette
Primary Outcome Measure Information:
Title
The safety and tolerability of escalating doses of vMCO-l administered via a single IVT in subjects with advanced Retinitis Pigmentosa
Description
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.
Time Frame
16 Weeks
Secondary Outcome Measure Information:
Title
Evaluate the treatment effect of vMCO-l as assessed by visual acuity
Description
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
Time Frame
52 weeks
Title
Evaluate the treatment effect of vMCO-l as assessed by Visually-guided Mobility assays
Description
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
Time Frame
52 weeks
Title
Evaluate the treatment effect of vMCO-l as assessed by Visually-guided Mobility assays
Description
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
Time Frame
52 weeks
Title
Evaluate the treatment effect of vMCO-l as assessed by Static Shape recognition assay
Description
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
Time Frame
52 weeks
Title
Evaluate the treatment effect of vMCO-l as assessed by Static Shape recognition assay
Description
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
Time Frame
52 weeks
Title
Evaluate the treatment effect of vMCO-l as assessed by Optical Flow assay
Description
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
Time Frame
52 weeks
Title
Evaluate the treatment effect of vMCO-l as assessed by Optical Flow assay
Description
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
Time Frame
52 weeks
Title
Evaluate the treatment effect of vMCO-l as assessed by Quality of Life Questionnaire
Description
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.
Time Frame
52 weeks
Title
Evaluate the treatment effect of vMCO-l as assessed by Humphrey Visual Field
Description
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.
Time Frame
52 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age > 18 years
Diagnosis of advanced RP using Fundus Photographs
Clinical diagnosis of advanced retinal dystrophy
Prior documented (if any) retinal electrophysiological evidence of rod-cone photoreceptor degeneration
Snellen's visual acuity equivalent LP/NLP in worse (study) eye
Visual acuity in the non-study eye of no-better-than finger counting
Presence of retinal bipolar cells and retinal nerve fiber layer on OCT testing
Exclusion Criteria:
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.
Concurrent participation in another interventional clinical ocular study.
Pre-existing eye conditions such as glaucoma, diseases affecting the optic nerve causing significant visual field loss, active uveitis, corneal or lenticular opacities).
Presence of any complicating systemic diseases such as malignancies whose treatment could affect central nervous system function.
Subjects who are positive for hepatitis B, C, and HIV will be excluded.
Subjects who have undergone ocular surgery in the study eye within three months prior to Day 0.
Presence of narrow iridocorneal angles contraindicating pupillary dilation in the study eye.
Known sensitivity to any component of the study agent or medications planned for use in the peri-operative period.
Subjects will be excluded if immunological studies show presence of neutralizing antibodies to AAV2 above 1:1000.
Presence of narrow iridocorneal angles contraindicating pupillary dilation.
Presence of disorders of the ocular media which interfere with visual acuity and other ocular assessments, including OCT, during the study period.
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.
Current evidence of retinal detachment assessed by the investigator to significantly affect central vision.
Active ocular inflammation or recurrent history of idiopathic or autoimmune associated uveitis.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Santosh Mahapatra, MD
Organizational Affiliation
JPM Rotary Club of Cuttack Eye Hospital and Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
JPM Rotary Club of Cuttack Eye Hospital and Research Institute
City
Cuttack
State/Province
Odisha
ZIP/Postal Code
753014
Country
India
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
Learn more about this trial
Dose-Escalation Study to Evaluate the Safety and Tolerability of Intravitreal vMCO-I in Patients With Advanced Retinitis Pigmentosa
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