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Gene Therapy for Achromatopsia (CNGB3)

NCT03001310 — Phase 1 / Phase 2, Completed, 23 participants, MeiraGTx UK II Ltd
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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 Defects in CNGB3

RegistryNCT03001310, acronym CNGB3
StatusCompleted
PhasePhase 1 / Phase 2
Study typeInterventional; non randomized, sequential, masking: none, treatment
Enrollment23 (Actual)
SponsorMeiraGTx UK II Ltd (Industry); collaborators: Janssen Research & Development, LLC
ConditionsAchromatopsia
InterventionsAAV - CNGB3 (Biological)
Datesstart 2017-01-16, primary completion 2019-10-25, completion 2019-10-25, first posted 2016-12-23, last updated 2023-03-08
Locations2 sites in United States, United Kingdom

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-Summary

A clinical trial of AAV - CNGB3 retinal gene therapy for patients with achromatopsia

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+Detailed description

CNGB3 retinal gene therapy for patients with achromatopsia

+Arms and interventions

ArmTypeInterventionsDescription
Biological-Low dose AAV - CNGB3ExperimentalBiological: AAV - CNGB3Subretinal administration of a single low dose of AAV - CNGB3
Biological-Medium dose AAV - CNGB3ExperimentalBiological: AAV - CNGB3Subretinal administration of a single intermediate dose of AAV - CNGB3
Biological-High dose AAV - CNGB3ExperimentalBiological: AAV - CNGB3Subretinal administration of a single high dose of AAV - CNGB3
  • AAV - CNGB3 (Biological): Comparison of different dosages of AAV-CNGB3

+Outcome measures

Primary outcomes

  • Number of Participants Meeting the Primary Outcome Defined as Any of the Below Events Occurring During the 6 Weeks Following Administration, at Least Possibly Related to the Advanced Therapy Investigational Medicinal Products (ATIMP), Not Surgery Alone. [6 weeks]: The primary outcome is defined as any of the below occurring during the 6 weeks following administration, at least possibly related to the Advanced Therapy Investigational Medicinal Products (ATIMP), not surgery alone: * Reduction in visual acuity by 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters or more that fails to resolve to within 15 letters of baseline in a 4-week period once prophylactic treatment commences * Severe unresponsive inflammation * Infective endophthalmitis * Ocular malignancy * Grade III or above non-ocular Suspected Unexpected Serious Adverse Reaction (SUSAR)

Secondary outcomes

  • Improvements in Visual Function as Assessed by Visual Acuity [6 months]: Change from baseline to Week 24 in best corrected visual acuity (BCVA) using Early Treatment Diabetic Retinopathy Study (ETDRS) chart letter score in the treated eye. The direction of improvement from baseline is an increase in the number of ETDRS letters read over time.
  • Improvements in Retinal Function as Assessed by Static Perimetry [6 months]: Change from baseline to Week 24 in mean retinal sensitivity in the treated eye. The direction of improvement is an increase in sensitivity.
  • Quality of Life Measured by QoL Questionnaires in Children and Adolescents [6 months]: Change from baseline to Week 24 in EuroQol-5D-Y Visual Analogue Scale (EQ-VAS) in children and adolescents. EQ-VAS uses a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. A positive change from baseline reflects improvement and a negative change from baseline reflects worsening.
  • Quality of Life Measured by QoL Questionnaires in Adults [6 Months]: Change from baseline to Week 24 in EuroQol-5D-5L Visual Analogue Scale (EQ-VAS) in adults. EQ-VAS uses a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. A positive change from baseline reflects improvement and a negative change from baseline reflects worsening.

+Eligibility

Sex: All, ages: 3 Years to any

Inclusion Criteria:

* Are aged 3 years or older
* Have achromatopsia confirmed by a retinal specialist (CI or PI)

Exclusion Criteria:

* Are females who are pregnant or breastfeeding
* Have participated in another research study involving an investigational medicinal therapy for ocular disease within the last 6 months
* Have any other condition that the CI/PI considers makes them inappropriate for entry into the trial

+Posted results

Participant flow

MilestoneLow Dose AAV - CNGB3Intermediate Dose AAV-CNGB3Other Dose - AAV - CNGB3High Dose AAV - CNGB3
Started31235
Completed31235
Not completed0000

Outcome results

  • Number of Participants Meeting the Primary Outcome Defined as Any of the Below Events Occurring During the 6 Weeks Following Administration, at Least Possibly Related to the Advanced Therapy Investigational Medicinal Products (ATIMP), Not Surgery Alone. (Primary), Count of participants, Participants: Low Dose AAV - CNGB3 0; Intermediate Dose AAV-CNGB3 1; Other Dose - AAV - CNGB3 0; High Dose AAV - CNGB3 2
  • Improvements in Visual Function as Assessed by Visual Acuity (Secondary), Mean, number of ETDRS letters: Low Dose AAV - CNGB3 -0.44 (-2.0 to 1.3); Intermediate Dose AAV-CNGB3 -0.58 (-4.3 to 3.3); Other Dose - AAV - CNGB3 1.78 (0.3 to 4.7); High Dose AAV - CNGB3 1.45 (-4.0 to 5.3)
  • Improvements in Retinal Function as Assessed by Static Perimetry (Secondary), Mean, decibel: Low Dose AAV - CNGB3 -1.58 (-3.1 to 0.0); Intermediate Dose AAV-CNGB3 -0.39 (-2.4 to 1.8); Other Dose - AAV - CNGB3 8.13 (1.7 to 11.4); High Dose AAV - CNGB3 -0.77 (-7.1 to 3.3)
  • Quality of Life Measured by QoL Questionnaires in Children and Adolescents (Secondary), Mean, units on a scale: Low Dose AAV - CNGB3 ; Intermediate Dose AAV-CNGB3 6.9 (-2 to 20); Other Dose - AAV - CNGB3 2.3 (-3 to 10); High Dose AAV - CNGB3 -9.0
  • Quality of Life Measured by QoL Questionnaires in Adults (Secondary), Mean, units on a scale: Low Dose AAV - CNGB3 0.0 (-10 to 10); Intermediate Dose AAV-CNGB3 -3.8 (-10 to 5); Other Dose - AAV - CNGB3 ; High Dose AAV - CNGB3 4.3 (-5 to 20)

Adverse events

Time frame: 6 months

ArmDeathsSerious adverse eventsOther adverse events
Low Dose AAV - CNGB30/3 (0.0%)0/3 (0.0%)3/3 (100.0%)
Intermediate Dose AAV-CNGB30/12 (0.0%)1/12 (8.3%)12/12 (100.0%)
Other Dose - AAV - CNGB30/3 (0.0%)0/3 (0.0%)3/3 (100.0%)
High Dose AAV - CNGB30/5 (0.0%)1/5 (20.0%)5/5 (100.0%)
Total0/23 (0.0%)2/23 (8.7%)23/23 (100.0%)

Serious adverse events by term

TermOrgan systemLow Dose AAV - CNGB3Intermediate Dose AAV-CNGB3Other Dose - AAV - CNGB3High Dose AAV - CNGB3Total
UveitisEye disorders0/31/120/31/52/23
Ectopic pregnancyPregnancy, puerperium and perinatal conditions0/31/120/30/51/23

Other adverse events by term

TermOrgan systemLow Dose AAV - CNGB3Intermediate Dose AAV-CNGB3Other Dose - AAV - CNGB3High Dose AAV - CNGB3Total
Conjunctival haemorrhageEye disorders3/310/122/35/520/23
Lenticular opacitiesEye disorders2/37/123/33/515/23
Visual acuity reducedEye disorders2/37/121/35/515/23
Subretinal fluidEye disorders2/34/120/33/59/23
Foreign body sensation in eyesEye disorders0/37/120/31/58/23
Ocular discomfortEye disorders0/35/120/33/58/23
Chorioretinal foldsEye disorders0/34/120/32/56/23
Retinal haemorrhageEye disorders2/32/120/32/56/23
Conjunctival hyperaemiaEye disorders0/33/121/30/54/23
Eye inflammationEye disorders1/31/122/30/54/23
MaculopathyEye disorders0/31/120/33/54/23
Retinal depigmentationEye disorders0/32/122/30/54/23
Retinal oedemaEye disorders0/32/120/32/54/23
Retinal tearEye disorders0/33/120/31/54/23
Eye painEye disorders0/32/121/30/53/23
PhotophobiaEye disorders0/32/120/31/53/23
Vitreous floatersEye disorders1/32/120/30/53/23
Conjunctival oedemaEye disorders0/32/120/30/52/23
Corneal disorderEye disorders0/31/120/31/52/23
Macular fibrosisEye disorders0/31/120/31/52/23
Retinal disorderEye disorders0/31/121/30/52/23
Retinal pigment epitheliopathyEye disorders0/32/120/30/52/23
UveitisEye disorders0/30/120/32/52/23
HeadacheNervous system disorders1/33/121/31/56/23
Visual field defectNervous system disorders0/34/120/31/55/23
DizzinessNervous system disorders2/31/120/31/54/23
RhinitisInfections and infestations0/34/120/31/55/23
Postoperative wound infectionInfections and infestations0/31/121/30/52/23
NauseaGastrointestinal disorders1/30/121/30/52/23
Intraocular pressure increasedInvestigations2/31/121/32/56/23
FatigueGeneral disorders0/32/120/31/53/23
CoughRespiratory, thoracic and mediastinal disorders0/32/120/30/52/23
RashSkin and subcutaneous tissue disorders0/31/120/31/52/23

+Locations (2)

FacilityCityCountryStatus
University of Michigan Kellog Eye CentreAnn Arbor, MichiganUnited States
Moorfields Eye Hospital NHS Foundation TrustLondonUnited Kingdom

+Publications

  • Results publication: Michaelides M, Hirji N, Wong SC, Besirli CG, Zaman S, Kumaran N, Georgiadis A, Smith AJ, Ripamonti C, Gottlob I, Robson AG, Thiadens A, Henderson RH, Fleck P, Anglade E, Dong X, Capuano G, Lu W, Berry P, Kane T, Naylor S, Georgiou M, Kalitzeos A, Ali RR, Forbes A, Bainbridge J. First-in-Human Gene Therapy Trial of AAV8-hCARp.hCNGB3 in Adults and Children With CNGB3-associated Achromatopsia. Am J Ophthalmol. 2023 Sep;253:243-251. doi: 10.1016/j.ajo.2023.05.009. Epub 2023 May 11. PMID 37172884

+Study documents

+Investigators

+Funding

NIH grants: 2016

My Notes