Trials Sponsors Conditions Drugs Pricing

Conditions

Leber Congenital Amaurosis

Keywords

Adeno-Associated Virus (AAV)Leber Congenital AmaurosisGene transfer

Outcome Measures

Primary Outcomes (1)

The primary outcome measures are safety and tolerability. Secondary outcome measure(s) include changes in visual function as measured by subjective, psychophysical tests and by objective, physiologic tests.
Visual function will be measured at designated intervals from baseline visits through 5 years as stated in the protocol.

Study Arms (3)

dose cohort 1

EXPERIMENTAL

1.5E10 vector genomes voretigene neparvovec-rzyl in 150 microliters administered subretinally

Biological: voretigene neparvovec-rzyl

dose cohort 2

EXPERIMENTAL

4.8E10 vector genomes voretigene neparvovec-rzyl in 150 microliters administered subretinally

Biological: voretigene neparvovec-rzyl

dose cohort 3

EXPERIMENTAL

1.5E11 vector genomes voretigene neparvovec-rzyl in 300 microliters administered subretinally

Interventions

voretigene neparvovec-rzylBiological

Subjects will be dosed unilaterally (one eye) beginning with the lowest dose. Subjects will be injected with AAV2-hRPE65v2 by means of a subretinal injection. Dose escalation to the next cohort will be dependent on assessment of the safety data by the DSMB out to at least 4 weeks following the injection. Because there is a delay between time of delivery of AAV2 and the peak transgene expression there will be a delay of six weeks between all subjects.

Also known as: AAV2-hRPE65v2

dose cohort 1dose cohort 2dose cohort 3

Registry-reported names are shown in full. Names without a link have not yet been matched to a Syfrah profile.

Eligibility Criteria

Age8 Years+

Sexall

Healthy VolunteersNo

Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

Male and female subjects of any ethnic group are eligible for participation in this study, providing they meet the following criteria:
Must be willing to adhere to protocol and companion protocol for long-term follow-up as evidenced by written informed consent or parental permission and subject assent.

Sponsors & Collaborators

Spark Therapeutics, Inc.
Industrylead

Study Sites (1)

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Related Publications (9)

Acland GM, Aguirre GD, Ray J, Zhang Q, Aleman TS, Cideciyan AV, Pearce-Kelling SE, Anand V, Zeng Y, Maguire AM, Jacobson SG, Hauswirth WW, Bennett J. Gene therapy restores vision in a canine model of childhood blindness. Nat Genet. 2001 May;28(1):92-5. doi: 10.1038/ng0501-92.
PMID: 11326284BACKGROUND
Acland GM, Aguirre GD, Bennett J, Aleman TS, Cideciyan AV, Bennicelli J, Dejneka NS, Pearce-Kelling SE, Maguire AM, Palczewski K, Hauswirth WW, Jacobson SG. Long-term restoration of rod and cone vision by single dose rAAV-mediated gene transfer to the retina in a canine model of childhood blindness. Mol Ther. 2005 Dec;12(6):1072-82. doi: 10.1016/j.ymthe.2005.08.008. Epub 2005 Oct 14.
PMID: 16226919BACKGROUND

MeSH Terms

Conditions

Leber Congenital Amaurosis

Condition Hierarchy (Ancestors)

Eye Diseases, HereditaryEye DiseasesRetinal Diseases

Study Officials

Clinical Director
Spark Therapeutics, Inc.
STUDY DIRECTOR

Study Design

Study Type: interventional
Phase: phase 1
Allocation: NON RANDOMIZED
Masking: NONE
Purpose: TREATMENT
Intervention Model: SINGLE GROUP
Sponsor Type: INDUSTRY
Responsible Party: SPONSOR

Study Record Dates

First Submitted

August 13, 2007

First Posted

August 15, 2007

Study Start

September 2007

Actual (reported)

Primary Completion

March 20, 2018

Actual (reported)

You may not qualify if:

SUBJECTS WILL NOT BE EXCLUDED BASED ON THEIR GENDER, RACE OR ETHNICITY.
Subjects who meet any of the following conditions are excluded from the clinical study:
Unable or unwilling to meet requirements of the study.
Participation in a clinical study with an investigational drug in the past six months.
Pre-existing eye conditions that would preclude the planned surgery or interfere with the interpretation of study endpoints (for example, glaucoma, corneal or lenticular opacities).
Lack of sufficient viable retinal cells as determined by non-invasive means, such as optical coherence tomography (OCT) and/or ophthalmoscopy. Specifically, if indirect ophthalmoscopy reveals less than 1 disc area of retina which is not involved by complete retinal degeneration (indicated by geographic atrophy, thinning with tapetal sheen, or confluent intraretinal pigment migration), these eyes will be excluded. In addition, in eyes where optical coherence tomography (OCT) scans of sufficient quality can be obtained, areas of retina with thickness measurements less than 100 um, or absence of neural retina, will not be targeted for delivery of AAV2-hRPE65v2.
Complicating systemic diseases or clinically significant abnormal baseline laboratory values. Complicating systemic diseases would include those in which the disease itself, or the treatment for the disease, can alter ocular function. Examples are malignancies whose treatment could affect central nervous system function (for example, radiation treatment of the orbit; leukemia with CNS/optic nerve involvement). Also excluded would be subjects with immuno-compromising diseases, as there could be susceptibility to opportunistic infection (such as CMV retinitis). Subjects with diabetes or sickle cell disease would be excluded if they had any manifestation of advanced retinopathy (e.g. macular edema or proliferative changes). Subjects with juvenile rheumatoid arthritis could be excluded due to increased infection risk after surgery due to poor wound healing. Subjects who are positive for hepatitis B, C, and HIV will be excluded.
Prior ocular surgery within six months.
Known sensitivity to medications planned for use in the peri-operative period.
Individuals of childbearing potential who are pregnant or unwilling to use effective contraception for the duration of the study.
Any other condition that would not allow the potential subject to complete follow-up examinations during the course of the study and, in the opinion of the investigator, makes the potential subject unsuitable for the study.
Subjects will be excluded if immunological studies show presence of neutralizing antibodies to AAV2 above 1:1000.

Safety Study in Subjects With Leber Congenital Amaurosis

Brief Summary

Registry Overview

Trial Relationships

Study Timeline

First Submitted

First Posted

Study Start

Primary Completion

Study Completion

Conditions

Keywords

Outcome Measures

Primary Outcomes (1)

Study Arms (3)

dose cohort 1

dose cohort 2

dose cohort 3

Interventions

Eligibility Criteria

You may qualify if:

Sponsors & Collaborators

Study Sites (1)

Related Publications (9)

MeSH Terms

Conditions

Condition Hierarchy (Ancestors)

Study Officials

Study Design

Study Record Dates

You may not qualify if:

Source record

Locations

Brief Summary

Registry Overview

Trial Relationships

Related Scientific Literature

Study Timeline

First Submitted

First Posted

Study Start

Primary Completion

Study Completion

Conditions

Keywords

Outcome Measures

Primary Outcomes (1)

Study Arms (3)

dose cohort 1

dose cohort 2

dose cohort 3

Interventions

Eligibility Criteria

You may qualify if:

Sponsors & Collaborators

Study Sites (1)

Related Publications (9)

MeSH Terms

Conditions

Condition Hierarchy (Ancestors)

Study Officials

Study Design

Study Record Dates

You may not qualify if:

Source record

Locations