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Trial record 3 of 18 for:    Leber congenital amaurosis

Natural History Study of Patients With Leber Congenital Amaurosis Associated With Mutations in RPE65

This study is currently recruiting participants.
See Contacts and Locations
Verified June 2016 by MeiraGTx UK II Ltd
Information provided by (Responsible Party):
MeiraGTx UK II Ltd Identifier:
First received: March 8, 2016
Last updated: June 8, 2016
Last verified: June 2016

The inherited retinal dystrophies are a clinically and genetically heterogeneous group of conditions, which often present in childhood. These disorders can be usefully divided according to whether they (i) are stationary or progressive; and (ii) exhibit predominantly rod or cone involvement, or central receptor disease. The underlying molecular genetic basis of the majority of monogenic inherited retinal disease has now been characterised.

Leber Congenital Amaurosis (LCA) is a diagnosis for a group of severe, autosomal recessively inherited rod - cone dystrophies that typically result in complete visual loss in the third or fourth decade of life. One form, LCA2, is caused by a mutation in the gene encoding RPE56, an RPE-specific 65-kDa isomerase. Non-functional RPE65 results in photoreceptor cells that are unable to respond to light resulting in these patients being visually impaired.

Proof of principle studies for RPE65 gene replacement therapy has been demonstrated with the use of recombinant adeno-associated virus serotype 2 (rAAV2/2) vectors in animal models. Furthermore clinical trials of gene replacement therapy in RPE65 associated LCA (RPE65-LCA) have shown significant promise. All three clinical trials showed improvement in visual function over the first year, however longer term follow up demonstrated progressive visual loss and that initial improvements were not maintained.

Greater efficacy was noted in animal models and we feel the relatively lower efficacy of treatment in participants was most likely due to insufficient production of RPE65 protein from AAV2/2 hRPE65 in the human eye. As the maximal tolerated vector dose had been reached for AAV2/2 hRPE65, an optimised therapeutic vector (AAV2/5-OPTIRPE65) has been developed to drive higher transgene expression levels. (Professor Robin Ali and Prof James Bainbridge - unpublished data).

In preparation for human clinical trials, a detailed prospective phenotypic study will be undertaken to investigate the natural history of RPE65-LCA. Such a study will help identify suitable patients for therapeutic intervention. Furthermore through greater phenotyping an optimal window for intervention and specific parameters to help quantify effect and identify clinical end points may have been ascertained .

Leber Congenital Amaurosis

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Natural History Study of Patients With Leber Congenital Amaurosis Associated With Mutations in RPE65

Resource links provided by NLM:

Further study details as provided by MeiraGTx UK II Ltd:

Primary Outcome Measures:
  • Analysis of retinal structure and function [ Time Frame: 6 years ]
    Retinal structure will be analysed using state of the art Adaptive optics and SD-OCT and Fundal autofluorescence. This will be correlated with assessment of visual acuity, psychophysical visual assessment, visual mobility, retinal sensitivity and visual fields

Secondary Outcome Measures:
  • Quality of Life Questionnaires [ Time Frame: 6 years ]
    Assessment of Visual impairment using appropriate, validated questionnaires

  • Retinal Sensitivity [ Time Frame: 6 years ]
    To be assessed in Microperimetry

  • Retinal Structural analysis with Adaptive Optics [ Time Frame: 6 years ]
    Retinal Structure analysis

  • Fundal Autofluorescence [ Time Frame: 6 years ]
    Presence or Absence

  • Assessment of Visual Fields [ Time Frame: 6 years ]
    Assessment of Visual Fields with analysis of hill of vision

Estimated Enrollment: 40
Study Start Date: April 2016
Estimated Study Completion Date: March 2021
Estimated Primary Completion Date: March 2021 (Final data collection date for primary outcome measure)
  Show Detailed Description


Ages Eligible for Study:   3 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients with RPE65-LCA condition

Inclusion Criteria:

  • Patients with RPE65 associated retinal dystrophy
  • Minimum subject age of 3 years
  • Able to give consent/parent or guardian able to give consent

Exclusion Criteria:

  • Patients unable or unwilling to undertake consent or clinical testing
  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 identifier: NCT02714816

Contact: Anna Morka, MSc 02037252350
Contact: Julie Bakobaki 02037252349

United States, Michigan
Kellogg Eye Center Not yet recruiting
Ann Arbor, Michigan, United States, MI 48105
Contact: Adrienne Chen    734-232-9167   
Contact: Anna Morka    02037252350   
Principal Investigator: John Heckenlively         
United Kingdom
Moorfields Eye Hospital Recruiting
London, United Kingdom
Contact: Neruban Kumaran, Dr   
Contact: Sophie Connor    02075662821   
Principal Investigator: Michel Michealides, Prof         
Sponsors and Collaborators
MeiraGTx UK II Ltd
Principal Investigator: Michel Michealides, Prof UCL/Moorfileds
  More Information

Responsible Party: MeiraGTx UK II Ltd Identifier: NCT02714816     History of Changes
Other Study ID Numbers: ATH-2015-001
Study First Received: March 8, 2016
Last Updated: June 8, 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Leber Congenital Amaurosis
Vision Disorders
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Eye Diseases
Signs and Symptoms
Eye Diseases, Hereditary
Retinal Diseases processed this record on July 25, 2017