A Phase 1/2 interventional study of AAV - CNGB3 in Achromatopsia, sponsored by MeiraGTx UK II Ltd. Completed at 2 sites in 2 countries. Open to participants aged 3 Years and older. Per ClinicalTrials.gov, last updated 2023-03-08.
Sponsored by MeiraGTx UK II Ltd · Phase 1/2, Interventional, and Treatment
A clinical trial of AAV - CNGB3 retinal gene therapy for patients with achromatopsia
CNGB3 retinal gene therapy for patients with achromatopsia
Exclusion Criteria:
Subretinal administration of a single low dose of AAV - CNGB3
Biological: AAV - CNGB3
Subretinal administration of a single intermediate dose of AAV - CNGB3
Biological: AAV - CNGB3
Subretinal administration of a single high dose of AAV - CNGB3
Biological: AAV - CNGB3
Comparison of different dosages of AAV-CNGB3
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.
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)
Time frame: 6 weeks
Improvements in Visual Function as Assessed by Visual Acuity
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.
Time frame: 6 months
Improvements in Retinal Function as Assessed by Static Perimetry
Change from baseline to Week 24 in mean retinal sensitivity in the treated eye. The direction of improvement is an increase in sensitivity.
Time frame: 6 months
Quality of Life Measured by QoL Questionnaires in Children and Adolescents
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.
Time frame: 6 months
Quality of Life Measured by QoL Questionnaires in Adults
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.
Time frame: 6 Months
Participants were recruited from medical centers in the United Kingdom (UK) and the United States (US). A total of 23 participants were enrolled in the study.
| Milestone | Low Dose AAV - CNGB3 | Intermediate Dose AAV-CNGB3 | Other Dose - AAV - CNGB3 | High Dose AAV - CNGB3 |
|---|---|---|---|---|
| Started | 3 | 12 | 3 | 5 |
| Completed | 3 | 12 | 3 | 5 |
| Not completed | 0 | 0 | 0 | 0 |
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)
| Participants | Low Dose AAV - CNGB3 | Intermediate Dose AAV-CNGB3 | Other Dose - AAV - CNGB3 | High Dose AAV - CNGB3 |
|---|---|---|---|---|
| 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. | 0 | 1 | 0 | 2 |
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.
| number of ETDRS letters | Low Dose AAV - CNGB3 | Intermediate Dose AAV-CNGB3 | Other Dose - AAV - CNGB3 | High Dose AAV - CNGB3 |
|---|---|---|---|---|
| Improvements in Visual Function as Assessed by Visual Acuity | -0.44 (-2.0 to 1.3) | -0.58 (-4.3 to 3.3) | 1.78 (0.3 to 4.7) | 1.45 (-4.0 to 5.3) |
Change from baseline to Week 24 in mean retinal sensitivity in the treated eye. The direction of improvement is an increase in sensitivity.
| decibel | Low Dose AAV - CNGB3 | Intermediate Dose AAV-CNGB3 | Other Dose - AAV - CNGB3 | High Dose AAV - CNGB3 |
|---|---|---|---|---|
| Improvements in Retinal Function as Assessed by Static Perimetry | -1.58 (-3.1 to 0.0) | -0.39 (-2.4 to 1.8) | 8.13 (1.7 to 11.4) | -0.77 (-7.1 to 3.3) |
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.
| units on a scale | Low Dose AAV - CNGB3 | Intermediate Dose AAV-CNGB3 | Other Dose - AAV - CNGB3 | High Dose AAV - CNGB3 |
|---|---|---|---|---|
| Quality of Life Measured by QoL Questionnaires in Children and Adolescents | — | 6.9 (-2 to 20) | 2.3 (-3 to 10) | -9.0 |
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.
| units on a scale | Low Dose AAV - CNGB3 | Intermediate Dose AAV-CNGB3 | Other Dose - AAV - CNGB3 | High Dose AAV - CNGB3 |
|---|---|---|---|---|
| Quality of Life Measured by QoL Questionnaires in Adults | 0.0 (-10 to 10) | -3.8 (-10 to 5) | — | 4.3 (-5 to 20) |
Collected over 6 months. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Low Dose AAV - CNGB3 | 0/3 (0%) | 0/3 (0%) | 3/3 (100%) |
| Intermediate Dose AAV-CNGB3 | 0/12 (0%) | 1/12 (8.3%) | 12/12 (100%) |
| Other Dose - AAV - CNGB3 | 0/3 (0%) | 0/3 (0%) | 3/3 (100%) |
| High Dose AAV - CNGB3 | 0/5 (0%) | 1/5 (20%) | 5/5 (100%) |
| Total | 0/23 (0%) | 2/23 (8.7%) | 23/23 (100%) |
| Event | Low Dose AAV - CNGB3 | Intermediate Dose AAV-CNGB3 | Other Dose - AAV - CNGB3 | High Dose AAV - CNGB3 | Total |
|---|---|---|---|---|---|
| UveitisEye disorders | 0/3 | 1/12 | 0/3 | 1/5 | 2/23 |
| Ectopic pregnancyPregnancy, puerperium and perinatal conditions | 0/3 | 1/12 | 0/3 | 0/5 | 1/23 |
| Event | Low Dose AAV - CNGB3 | Intermediate Dose AAV-CNGB3 | Other Dose - AAV - CNGB3 | High Dose AAV - CNGB3 | Total |
|---|---|---|---|---|---|
| Conjunctival haemorrhageEye disorders | 3/3 | 10/12 | 2/3 | 5/5 | 20/23 |
| Lenticular opacitiesEye disorders | 2/3 | 7/12 | 3/3 | 3/5 | 15/23 |
| Visual acuity reducedEye disorders | 2/3 | 7/12 | 1/3 | 5/5 | 15/23 |
| Subretinal fluidEye disorders | 2/3 | 4/12 | 0/3 | 3/5 | 9/23 |
| Retinal haemorrhageEye disorders | 2/3 | 2/12 | 0/3 | 2/5 | 6/23 |
| Eye inflammationEye disorders | 1/3 | 1/12 | 2/3 | 0/5 | 4/23 |
| Retinal depigmentationEye disorders | 0/3 | 2/12 | 2/3 | 0/5 | 4/23 |
| DizzinessNervous system disorders | 2/3 | 1/12 | 0/3 | 1/5 | 4/23 |
| Intraocular pressure increasedInvestigations | 2/3 | 1/12 | 1/3 | 2/5 | 6/23 |
| Ocular discomfortEye disorders | 0/3 | 5/12 | 0/3 | 3/5 | 8/23 |
| Age, Categorical(Participants) | Low Dose AAV - CNGB3 | Intermediate Dose AAV-CNGB3 | Other Dose - AAV - CNGB3 | High Dose AAV - CNGB3 | Total |
|---|---|---|---|---|---|
| <=18 years | 0 | 8 | 3 | 2 | 13 |
| Between 18 and 65 years | 3 | 4 | 0 | 3 | 10 |
| >=65 years | 0 | 0 | 0 | 0 | 0 |
| Sex: Female, Male(Participants) | Low Dose AAV - CNGB3 | Intermediate Dose AAV-CNGB3 | Other Dose - AAV - CNGB3 | High Dose AAV - CNGB3 | Total |
|---|---|---|---|---|---|
| Female | 2 | 10 | 3 | 3 | 18 |
| Male | 1 | 2 | 0 | 2 | 5 |
| Ethnicity (NIH/OMB)(Participants) | Low Dose AAV - CNGB3 | Intermediate Dose AAV-CNGB3 | Other Dose - AAV - CNGB3 | High Dose AAV - CNGB3 | Total |
|---|---|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 | 0 | 0 |
| Not Hispanic or Latino | 3 | 12 | 3 | 5 | 23 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Low Dose AAV - CNGB3 | Intermediate Dose AAV-CNGB3 | Other Dose - AAV - CNGB3 | High Dose AAV - CNGB3 | Total |
|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 | 0 | 0 |
| White | 3 | 12 | 3 | 5 | 23 |
| More than one race | 0 | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 |
| Region of Enrollment(participants) | Low Dose AAV - CNGB3 | Intermediate Dose AAV-CNGB3 | Other Dose - AAV - CNGB3 | High Dose AAV - CNGB3 | Total |
|---|---|---|---|---|---|
| United States | 0 | 1 | 2 | 0 | 3 |
| United Kingdom | 3 | 11 | 1 | 5 | 20 |
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MeiraGTx UK II Ltd