Choroideremia Gene Therapy Clinical Trial

• Sponsor: Byron Lam (Other)
• Overall Status: Completed
• CT.gov ID: NCT02553135
• Collaborator: (none)
• Enrollment: 6
• Location: 1
• Arm: 1
• Actual Duration (Months): 29
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Phase II gene therapy study, involving a total of 6 male patients with choroideremia. The study will be conducted at the Bascom Palmer Eye Institute, University of Miami. Patients will be required to attend a total of 11 study visits over a 24 month period with an additional 3 year follow-up.

Condition or Disease	Intervention/Treatment	Phase
Choroideremia	Biological: Injection of AAV2-REP1 (10e11 vg)	Phase 2

Detailed Description

This is a Phase II, open label study involving patients with a clinical phenotype of choroideremia and a confirmed CHM genotype. Following consent, patients will be required to attend an initial screening visit (Visit 1). Within 2 weeks of the screening visit patients will undergo a surgical procedure (Visit 2) under general anesthesia which will include a standard vitrectomy, retinal detachment and administration of a subretinal injection of AAV2-REP1 (1x1011 genome particles). Patients will be required to attend a further 9 study visits (Visits 3-11) over a 24 month period for functional, and anatomical assessments as well as monitoring of adverse events. The primary endpoint is the change from baseline in visual acuity in the study eye, compared to control eye. Secondary study endpoints are, change from baseline in autofluorescence evaluation, microperimetry readings and other anatomic and functional outcomes (all in the study eye compared to control eye). Secondary endpoints also include safety assessments to be conducted throughout the study. The fellow eyes of these patients will be utilized as controls in this study and will receive no study treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label Phase 2 Clinical Trial of Retinal Gene Therapy for Choroideremia Using an Adeno-associated Viral Vector (AAV2) Encoding Rab-escort Protein 1 (REP1)
• Actual Study Start Date: Sep 1, 2015
• Actual Primary Completion Date: Feb 1, 2018
• Actual Study Completion Date: Feb 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Injection of AAV2-REP1 Injection of AAV-REP1, 1.00x10e11 vg, subretinal injection of total volume of 100 μL.	Biological: Injection of AAV2-REP1 (10e11 vg); Single Group: single arm study

Outcome Measures

Primary Outcome Measures

1. Change in Best Corrected Visual Acuity From Baseline [Baseline, 24 Months]

   Patients will have an assessment of visual acuity using the Early Treatment of Diabetic Retinopathy Study (ETDRS) vision charts in both eyes. Low Luminance BCVA was measured by placing a 2.0 log unit neutral density filter over the best correction for that eye and having the participant read the normally illuminated ETDRS chart and was reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). The study eye was defined as the eye that met inclusion/exclusion criteria with the worst standard BCVA. If the BCVA in both eyes was similar the Patient determines the worse eye be selected as the study eye. A positive change from baseline indicates an improvement and a negative change from baseline indicates a worsening.

Secondary Outcome Measures

1. Change in Retinal Macular Autofluorescence From Baseline [12 and 24 months]

   Measured in mm^2 by Fundus Autofluorescence and shows changes in the integrity and metabolism of retinal cells. A negative change from baseline indicates a decrease in size of the retained retina (worsening; disease progression).

2. Changes in Microperimetry From Baseline [Baseline to 24 months]

   Microperimetry assessments. A negative change from baseline indicates disease worsening.

3. Number of Participants Who Experience an Adverse Event [24 months]

   Adverse events during treatment and follow-up period

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 18 Years and older

• Male

• Able to give informed consent

• Genetically confirmed diagnosis of choroideremia

• Active disease visible clinically within the macula region

• Best-corrected visual acuity equal to or worse than 20/32 but better than or equal to 20/200 in the study eye.

Exclusion Criteria:

• Female

• Under the age of 18

• History of amblyopia in the study eye

• Men unwilling to use barrier contraception methods

• Relevant grossly asymmetrical disease or other ocular morbidity which might confound use of the fellow eye as a long-term control

• Any other significant ocular and non-ocular disease/disorder or retinal surgery

• Contraindication to use of medications or contrast agents

• Participated in research study involving an investigational product in the past 12 weeks

• Having had gene or cellular therapy at any time prior to this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Bascom Palmer Eye Institute, University of Miami	Miami	Florida	United States	33136

Sponsors and Collaborators

• Byron Lam

Investigators

• Principal Investigator: BYRON LAM, MD, UNIVERSITY OF MIAMI, BASCOM PALMER EYE INSTITUTE

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 18, 2015

More Information

Publications

None provided.

• Responsible Party: Byron Lam, Professor of Ophthalmology, University of Miami
• ClinicalTrials.gov Identifier: NCT02553135
• Other Study ID Numbers: 20150371
• First Posted: Sep 17, 2015
• Last Update Posted: Jul 29, 2019
• Last Verified: Jul 1, 2019

• Keywords provided by Byron Lam, Professor of Ophthalmology, University of Miami: choroideremia, gene therapy
• Additional relevant MeSH terms: Choroideremia

Study Results

Participant Flow

Arm/Group Title	Injection of AAV2-REP1
Arm/Group Description	Injection of AAV-REP1, 1.00x10e11 vg, subretinal injection of total volume of 100 μL. Injection of AAV2-REP1 (10e11 vg): Single Group: single arm study
Period Title: Overall Study
STARTED	6
COMPLETED	6
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Injection of AAV2-REP1
Arm/Group Description	Injection of AAV-REP1, 1.00x10e11 vg, subretinal injection of total volume of 100 μL. Injection of AAV2-REP1 (10e11 vg): Single Group: single arm study
Overall Participants	6
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	5 83.3%
>=65 years	1 16.7%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	6 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 16.7%
Not Hispanic or Latino	5 83.3%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	6 100%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Change in Best Corrected Visual Acuity From Baseline
Description	Patients will have an assessment of visual acuity using the Early Treatment of Diabetic Retinopathy Study (ETDRS) vision charts in both eyes. Low Luminance BCVA was measured by placing a 2.0 log unit neutral density filter over the best correction for that eye and having the participant read the normally illuminated ETDRS chart and was reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). The study eye was defined as the eye that met inclusion/exclusion criteria with the worst standard BCVA. If the BCVA in both eyes was similar the Patient determines the worse eye be selected as the study eye. A positive change from baseline indicates an improvement and a negative change from baseline indicates a worsening.
Time Frame	Baseline, 24 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Injection of AAV2-REP1
Arm/Group Description	Injection of AAV-REP1, 1.00x10e11 vg, subretinal injection of total volume of 100 μL. Injection of AAV2-REP1 (10e11 vg): Single Group: single arm study
Measure Participants	6
Mean (Standard Deviation) [Letters]	3.0 (4.0)

2. Secondary Outcome

Title	Change in Retinal Macular Autofluorescence From Baseline
Description	Measured in mm^2 by Fundus Autofluorescence and shows changes in the integrity and metabolism of retinal cells. A negative change from baseline indicates a decrease in size of the retained retina (worsening; disease progression).
Time Frame	12 and 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Injection of AAV2-REP1
Arm/Group Description	Injection of AAV-REP1, 1.00x10e11 vg, subretinal injection of total volume of 100 μL. Injection of AAV2-REP1 (10e11 vg): Single Group: single arm study
Measure Participants	6
Baseline to 12 Months	-3.4 (3.6)
Baseline to 24 Months	2.8 (2.9)

3. Secondary Outcome

Title	Changes in Microperimetry From Baseline
Description	Microperimetry assessments. A negative change from baseline indicates disease worsening.
Time Frame	Baseline to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Injection of AAV2-REP1
Arm/Group Description	Injection of AAV-REP1, 1.00x10e11 vg, subretinal injection of total volume of 100 μL. Injection of AAV2-REP1 (10e11 vg): Single Group: single arm study
Measure Participants	6
Mean (Standard Deviation) [Average Threshold dB]	0.823 (1.789)

4. Secondary Outcome

Title	Number of Participants Who Experience an Adverse Event
Description	Adverse events during treatment and follow-up period
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Injection of AAV2-REP1
Arm/Group Description	Injection of AAV-REP1, 1.00x10e11 vg, subretinal injection of total volume of 100 μL. Injection of AAV2-REP1 (10e11 vg): Single Group: single arm study
Measure Participants	6
Count of Participants [Participants]	6 100%

Adverse Events

Time Frame	24 months
Arm/Group Title	Injection of AAV2-REP1
Arm/Group Description	Injection of AAV-REP1, 1.00x10e11 vg, subretinal injection of total volume of 100 μL. Injection of AAV2-REP1 (10e11 vg): Single Group: single arm study
All Cause Mortality
	Injection of AAV2-REP1
	Affected / at Risk (%)	# Events
Total	0/6 (0%)
Serious Adverse Events
	Injection of AAV2-REP1
	Affected / at Risk (%)	# Events
Total	0/6 (0%)
Other (Not Including Serious) Adverse Events
	Injection of AAV2-REP1
	Affected / at Risk (%)	# Events
Total	6/6 (100%)
Eye disorders
Cataract	1/6 (16.7%)
Diplopia	1/6 (16.7%)
Vitreous Cells	1/6 (16.7%)
Anterior Chamber Cells	1/6 (16.7%)
Extrafoveal macular retinal hole in area of nonfunctioning retina	2/6 (33.3%)
Subretinal fluid	5/6 (83.3%)
Conjunctiva hemorrhage, edema	6/6 (100%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.