Phase I Trial of Gene Vector to Patients With Retinal Disease Due to RPE65 Mutations
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Ocular |
| Therapuetic Areas: | Ophthalmology |
| Healthy: | No |
| Age Range: | 8 - Any |
| Updated: | 10/17/2018 |
| Start Date: | July 2007 |
| End Date: | June 2026 |
Phase I Trial of Ocular Subretinal Injection of a Recombinant Adeno-Associated Virus (rAAV2-CBSB-hRPE65) Gene Vector to Patients With Retinal Disease Due to RPE65 Mutations (Clinical Trials of Gene Therapy for Leber Congenital Amaurosis)
A recombinant adeno-associated virus serotype 2 (rAAV2) vector has been altered to carry the
human RPE65 (hRPE65) gene. This vector has been shown to restore vision in animal models that
resemble human RPE65-associated Leber congenital amaurosis (LCA), an incurable retinal
degeneration that causes severe vision loss. The proposed study is an open label, Phase I
clinical trial of subretinal rAAV2-CBSB-hRPE65 administration to individuals with
RPE65-associated retinal disease. Five cohorts will be included in this trial. Cohorts 1, 2
and 4 will consist of individuals 18 years of age and older. Cohorts 3 and 5 will consist of
individuals between the ages of 8 and 17, inclusive. Enrollment in Cohorts 3 and 5 will begin
only after confirming the safety of rAAV2-CBSB-hRPE65 administration in the older groups of
participants. This trial will lead to a greater understanding of the safety and thereby
potential value of gene transfer in RPE65-associated retinal disease and will have
implications for other forms of retinal degenerative disease amenable to this type of
intervention.
The goal of this clinical trial is to determine the safety of uniocular subretinal
administration of rAAV2-CBSB-hRPE65 in individuals with RPE65-associated retinal disease.
Ocular and systemic toxicity will be assessed prior to and following vector administration to
determine if there are adverse changes that may be associated with vector administration.
human RPE65 (hRPE65) gene. This vector has been shown to restore vision in animal models that
resemble human RPE65-associated Leber congenital amaurosis (LCA), an incurable retinal
degeneration that causes severe vision loss. The proposed study is an open label, Phase I
clinical trial of subretinal rAAV2-CBSB-hRPE65 administration to individuals with
RPE65-associated retinal disease. Five cohorts will be included in this trial. Cohorts 1, 2
and 4 will consist of individuals 18 years of age and older. Cohorts 3 and 5 will consist of
individuals between the ages of 8 and 17, inclusive. Enrollment in Cohorts 3 and 5 will begin
only after confirming the safety of rAAV2-CBSB-hRPE65 administration in the older groups of
participants. This trial will lead to a greater understanding of the safety and thereby
potential value of gene transfer in RPE65-associated retinal disease and will have
implications for other forms of retinal degenerative disease amenable to this type of
intervention.
The goal of this clinical trial is to determine the safety of uniocular subretinal
administration of rAAV2-CBSB-hRPE65 in individuals with RPE65-associated retinal disease.
Ocular and systemic toxicity will be assessed prior to and following vector administration to
determine if there are adverse changes that may be associated with vector administration.
Inclusion Criteria:
- RPE65-associated retinal disease (two disease-causing RPE65 mutations);
- Clinical diagnosis of Leber congenital amaurosis (LCA)/early-onset retinal
degeneration (EORD) and of severely impaired visual and retinal function, and best
corrected visual acuity of 20/40 or worse in the study eye;
- Ability to perform tests of visual and retinal function;
- Visible photoreceptor layer on a standard OCT scan;
- Good general health;
- Ability to comply with research procedures;
- Specific for Cohorts 1, 2 and 4: 18 years of age and older;
- Specific for Cohorts 3 and 5: Between 8 and 17 years of age, inclusive.
Exclusion Criteria:
- AAV antibody titers greater than two standard deviations above normal at baseline;
- Humoral immune deficiency as evidenced by low tetanus toxoid IgG antibody titers;
- Pre-existing eye conditions that would preclude the planned surgery or interfere with
the interpretation of study endpoints or surgical complications;
- Complicating systemic diseases;
- Use of anti-platelet agents that may alter coagulation within 7 days prior to study
agent administration;
- Use of immunosuppressive medications;
- Pregnancy or breastfeeding;
- Individuals (males and females) of childbearing potential who are unwilling to use
effective contraception;
- Any condition that would prevent a subject from completing follow-up examinations
during the course of the study;
- Any condition that makes the subject unsuitable for the study;
- Current, or recent participation, in any other research protocol involving
investigational agents or therapies;
- Recent receipt of an investigational biologic therapeutic agent.
We found this trial at
2
sites
1600 SW Archer Rd # N5503
Gainesville, Florida 32610
Gainesville, Florida 32610
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