Safety and Efficacy of a Single Subretinal Injection of rAAV.hCNGA3 in Patients With CNGA3-linked Achromatopsia

This study is ongoing, but not recruiting participants.

Sponsor:

Collaborators:

University Hospital Tuebingen

Ludwig-Maximilians - University of Munich

Information provided by (Responsible Party):

STZ eyetrial

ClinicalTrials.gov Identifier:

NCT02610582

First received: September 18, 2015

Last updated: May 3, 2017

Last verified: May 2017

History of Changes

Purpose

The purpose of this study is to proof the safety and efficacy of a single subretinal injection of rAAV.hCNGA3 in patients with CNGA3-linked achromatopsia.

Condition	Intervention	Phase
Achromatopsia	Drug: rAAV.hCNGA3	Phase 1 Phase 2


Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: None (Open Label) Masking Description: open label Primary Purpose: Treatment
Official Title:	Safety and Efficacy of a Single Subretinal Injection of rAAV.hCNGA3 in Patients With CNGA3-linked Achromatopsia Investigated in an Exploratory, Dose-escalation Trial

Resource links provided by NLM:

Genetics Home Reference related topics: achromatopsia color vision deficiency

U.S. FDA Resources

Further study details as provided by STZ eyetrial:

Primary Outcome Measures:

Safety (AE). Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment [ Time Frame: Day 0 - Day 365 ]
Safety as the primary endpoint will be assessed by clinical examination of ocular inflammation (slit lamp, fundus biomicroscopy, angiography, perimetry or electrophysiology). Systemic safety will be assessed by vital signs, routine clinical chemistry testing (including C reactive protein, ESR) and full/differential blood counts. Immunopathology essays will include specific enzyme-linked immunosorbent assays for humoral antibodies against rAAV8 capsid protein and/or CNGA3 gene product and specific enzyme-linked immunosorbent spot assays to monitor cellular immune reactivity against rAAV8 capsid protein and/or CNGA3 gene product. Biodistribution will be monitored by polymerase chain reaction studies on rAAV8 genome in blood, urine, saliva and lachrymal fluid.

Secondary Outcome Measures:

Efficacy measures. Number of Participants With improved Visual Function. [ Time Frame: Day 14 - Day 365 ]
Efficacy data (improvement in visual function) and patient reported outcomes will be investigated exploratively as well as retinal imaging. They are all secondary endpoints in this trial.


Estimated Enrollment:	9
Study Start Date:	November 2015
Estimated Study Completion Date:	November 2017
Estimated Primary Completion Date:	November 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Single Arm dose escalation rAAVhCNGA3 low dose: ≤ 1x10e10 vgp (n=3) intermediate dose: ≤ 5x10e10 vgp (n=3) high dose: ≤ 1x10e11 vgp (n=3)	Drug: rAAV.hCNGA3 Single subretinal injection of rAAV.hCNGA3

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Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

clinical diagnosis of achromatopsia
≥ 18 years of age
confirmed mutation in CNGA3
BCVA ≥ 20/400
a minimal outer nuclear layer thickness of 10µm at 3° eccentricity in the study eye (normal = 38±6µm)
ability to understand and willingness to consent to study protocol
no infection with Human Immunodeficiency Virus (HIV)
negative pregnancy test in women with childbearing potential (a woman who is two years post-menopausal or surgically sterile is not considered to be of childbearing potential)

Exclusion Criteria:

additional interfering eye conditions (e.g. uveitis, advanced cataract) in the study eye
systemic conditions (e.g. coronary heart disease, autoimmune disorders) which may affect study participation or outcome measures
current or recent participation in other study/or administration of biologic agent within the last three months
recent (6 months) ocular surgery, intravitreal or subretinal implantation of a medical device
known sensitivity to any compound used in the study
contraindications to systemic immunosuppression
subject/partner of childbearing potential unwilling to use adequate contraception for four months
nursing or pregnant women
any other cause that, in the investigator's opinion, renders potential subjects not suitable for the study
mutations in another achromatopsia gene
contraindications in view of the planned surgery (e.g. anaemia Hb<8g/dl, severe coagulopathy, severe blood pressure fluctuations)
ocular opacity and mature cataract
history of ocular malignancies
disorders of the internal retina (e.g. retinal detachment in the patients history)
glaucoma defined as damage of the optic nerve
vascular retinal occlusion
diabetic patients suffering from retinopathy and/or macula edema
patients treated with oral corticoids within 14 days prior inclusion
systemic illness or medically significant abnormal laboratory values in blood analysis including renal and hepatic functions at inclusion
absence of vision on the other contralateral eye

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02610582

Locations


Germany
University Hospital Tuebingen, Center for Ophthalmology
Tuebingen, Germany, 72076

Sponsors and Collaborators

STZ eyetrial

University Hospital Tuebingen

Ludwig-Maximilians - University of Munich

Investigators


Principal Investigator:	Dominik Fischer, Prof.	University Hospital Tuebingen, Center for Ophthalmology

More Information


Responsible Party:	STZ eyetrial
ClinicalTrials.gov Identifier:	NCT02610582 History of Changes
Other Study ID Numbers:	RDC-CNGA3-01 2014-001874-32 ( EudraCT Number ) 096/2015 AMG1 ( Other Identifier: Ethics Committee Tübingen )
Study First Received:	September 18, 2015
Last Updated:	May 3, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Keywords provided by STZ eyetrial:


CNGA3-linked

Additional relevant MeSH terms:


Color Vision Defects Vision Disorders Sensation Disorders Neurologic Manifestations	Nervous System Diseases Eye Diseases Signs and Symptoms

ClinicalTrials.gov processed this record on September 21, 2017

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