Clinical Trial: Gene Therapy for Achromatopsia (CNGB3)

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: An Open Label, Multi-centre, Phase I/II Dose Escalation Trial of a Recombinant Adeno-associated Virus Vector (AAV2/8-hCARp.hCNGB3) for Gene Therapy of Adults and Children With Achromatopsia Owing to D

Brief Summary:

Achromatopsia is a recessively inherited condition characterised by a lack of cone photoreceptor function resulting in impairment of colour vision and visual acuity, central scotoma often with eccentric fixation, disabling hypersensitivity to light (photophobia) and involuntary eye movements (pendular nystagmus).

Children with CNGB3-related achromatopsia have profound sight impairment from birth or early infancy. The condition is currently untreatable, but there is a real possibility that a gene therapy could offer a significant benefit in terms of improved sight and quality of life (QOL), based on our own and others experience of ocular gene therapy trials )and pre-clinical data demonstrating improved outcome in CNGB3- related achromatopsia. Possible benefits of improved cone-photoreceptor function include improved visual acuity; improved colour perception; and relief from disabling photophobia. Although younger individuals may benefit most from gene supplementation therapy by virtue of their greater visual plasticity, it is anticipated that the intervention may offer benefit across a range of ages and the aim is to define this range. For this reason, participants of various ages will be included; children will be included only after an acceptable safety profile has been established in adults.

Detailed Summary:

The purpose of this trial is to determine the safety and efficacy of subretinal administration of the ATIMP in participants with CNGB3-related achromatopsia. Since this is primarily a safety study and assessments of efficacy will be explored in nature, a control group won't be included and will only enrol patients with CNBG3 mutations. Since this is a rare disease, only a small number of participants (up to 27) will be recruited. This study will be conducted at two academic hospitals: one in the UK and one in the USA.

In the dose escalation phase, up to 18 adult participants will be administered one of 3 different doses of the ATIMP in cohorts of 3 participants at a time. Based on toxicity data, the IDMC will make a recommendation on the dose to administer to the next cohort of 3 participants. The IDMC may recommend an additional 1 or 2 participants at a given dose before deciding how to proceed.

Once an acceptable safety profile has been established in adults, up to 9 additional participants, who may be children or adults, will be included. The IDMC will agree the maximum tolerated dose in adults before recommending administering this dose to children.

During the study the participants will make 13 visits to the study site over a period of six to nine months to measure parameters of safety and efficacy of the intervention. Participants will attend a screening visit to ensure eligibility for the study, three baseline visits to establish reference measurement, a visit where they will undergo an operation to deliver the normal CNGB3 gene to the eye and eight follow-up visits within the six months after the operation to make sure the operation is safe and to measure whether there are any improvements in sight. The visits before and after the operation are designed to ensure th
Sponsor: MeiraGTx UK II Ltd

Current Primary Outcome: Incidence of Adverse Events related to the sub retinal administration of an AAV2/8 vector. [ Time Frame: 6 months ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Improvement in the visual function [ Time Frame: 6 months ]
  • Any improvements in visual function from baseline that are greater than the test-retest variation and are sustained for at least two consecutive assessments.
• Improvement in retinal function [ Time Frame: 6 months ]
  • Any improvement in retinal function from baseline that is measurable by electroretinography (ERG).
• Improvement in Quality of life [ Time Frame: 6 months ]
  Quality of life is measured by the Impact of Visual Impairment (IVI) questionnaire and the EQ5D-5L

Original Secondary Outcome: Same as current

Information By: MeiraGTx UK II Ltd

Dates:
Date Received: November 22, 2016
Date Started: January 12, 2016
Date Completion: December 2018
Last Updated: February 22, 2017
Last Verified: February 2017