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TerminatedNCT03278873Updated Jun 11, 2025Results posted

Long-Term Follow-Up Gene Therapy Study for Achromatopsia CNGB3 and CNGA3

An observational study in Achromatopsia, sponsored by MeiraGTx UK II Ltd. Terminated at 2 sites in 2 countries. Open to participants aged 3 Years to 100 Years. Per ClinicalTrials.gov, last updated 2025-06-11.

Sponsored by MeiraGTx UK II Ltd · Observational

Why this study was terminated
Strategic decision to not further develop AAV8-hCARp.hCNGB3 and AAV8-hG1.7p.coCNGA3. The decision is not due to safety concerns.
Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
34
Ages
3 Years to 100 Years
Sex
All
01

Study summary

This is a longer-term follow-up study of patients with achromatopsia associated with defects in CNGA3 who participated in a clinical trial in which they received AAV-CNGA3 retinal gene therapy, or of patients with achromatopsia associated with defects in CNGB3 who participated in a clinical trial in which they received AAV-CNGB3 retinal gene therapy.

Read the detailed description

The follow-up study is designed to collect data on the longer-term safety and efficacy of AAV-CNGA3 retinal gene therapy and AAV-CNGB3 retinal gene therapy.

02

Conditions studied

  • Achromatopsia

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Keywords

  • Achromatopsia
  • CNGA3
  • CNGB3
03

Who can participate

Ages eligible
3 Years to 100 Years
Sexes eligible
All
Accepts healthy volunteers
No
Sampling method
Non-probability sample

Study population

The study population are adults and children with achromatopsia resulting from mutations in CNGA3 or CNGB3.

Eligibility criteria

Inclusion in the study will be limited to individuals who:

  1. Are able to give informed consent or assent, with or without the guidance of their parent(s)/guardian(s), where appropriate
  2. Received AAV2/8-hCARp.hCNGB3 or AAV2/8-hG1.7p.coCNGA3 by intraocular administration in the prior open-label, Phase I/II, dose escalation study (EudraCT 2016-002290-35 or EudraCT 2018-003431-29)
  3. Are willing to adhere to the protocol and long-term follow-up

Individuals will be excluded who:

Are unwilling or unable to meet the requirements of the study

04

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
34 participants (actual)
Patient registry
No

Groups and cohorts

  • Low dose of AAV-CNGA3 or AAV-CNGB3

    Subretinal administration of a single low dose of AAV-CNGA3 or AAV-CNGB3

    Biological: Prior exposure to AAV-CNGA3 or AAV-CNGB3

  • Intermediate dose of AAV-CNGA3 or AAV-CNGB3

    Subretinal administration of a single intermediate dose of AAV-CNGA3 or AAV-CNGB3

    Biological: Prior exposure to AAV-CNGA3 or AAV-CNGB3

  • Other dose of AAV-CNGA3 or AAV-CNGB3

    Subretinal administration of a single other dose (between the intermediate and high dose) of AAV-CNGA3 or AAV-CNGB3

    Biological: Prior exposure to AAV-CNGA3 or AAV-CNGB3

  • High dose of AAV-CNGA3 or AAV-CNGB3

    Subretinal administration of a single high dose of AAV-CNGA3 or AAV-CNGB3

    Biological: Prior exposure to AAV-CNGA3 or AAV-CNGB3

Interventions

  • BiologicalPrior exposure to AAV-CNGA3 or AAV-CNGB3

    Participants previously received AAV-CNGA3 or AAV-CNGB3 in an open-label, Phase 1/2 dose escalation trial for adults and children with achromatopsia owing to defects in CNGA3 or CNGB3, respectively.

05

What researchers measure

Primary outcomes

  1. Incidence of Adverse Events Related to the Treatment

    The primary outcome measure is the longer-term safety of treatment with AAV-CNGA3 or AAV-CNGB3, assessed by the absence of IMP-related adverse events.

    Time frame: 5 Years

Secondary outcomes

  1. Improvements in Visual Function as Assessed by Visual Acuity at Month 12

    Change from baseline to Month 12 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: 12 months

  2. Improvements in Visual Function as Assessed by Visual Acuity at Month 60

    Change from baseline to Month 60 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: 60 months

  3. Improvements in Retinal Function as Assessed by Static Perimetry at Month 12

    Change from baseline to Month 12 in contrast sensitivity in the treated eye. The direction of improvement is an increase in sensitivity.

    Time frame: 12 months

  4. Improvements in Retinal Function as Assessed by Static Perimetry at Month 60

    Change from baseline to Month 60 in contrast sensitivity in the treated eye. The direction of improvement is an increase in sensitivity.

    Time frame: 60 months

  5. Quality of Life at Month 12 Measured by QoL Questionnaires in Children and Adolescents

    Change from baseline to Month 12 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: 12 months

  6. Quality of Life at Month 60 Measured by QoL Questionnaires in Children and Adolescents

    Change from baseline to Month 60 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: 60 months

  7. Quality of Life at Month 12 Measured by QoL Questionnaires in Adults

    Change from baseline to Month 12 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: 12 months

  8. Quality of Life at Month 60 Measured by QoL Questionnaires in Adults

    Change from baseline to Month 60 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: 60 months

06

Results

Posted Jun 11, 2025
Limitations and caveats
Upon agreement with the FDA, the study was prematurely terminated in March 2024. Therefore, the Month 60 data are not available for all participants.

Participant flow

Participants were recruited from medical centers in the United Kingdom (UK) and the United States (US). A total of 34 participants were enrolled in the study.

Participant flow — Overall Study
MilestoneLow Dose of AAV-CNGA3 or AAV-CNGB3Intermediate Dose of AAV-CNGA3 or AAV-CNGB3Other Dose of AAV-CNGA3 or AAV-CNGB3High Dose of AAV-CNGA3 or AAV-CNGB3
Started615310
Completed3602
Not completed3938
Withdrew: Withdrawal by subject0100
Withdrew: Sponsor's decision0100
Withdrew: Early termination2604
Withdrew: Lost to follow-up0020
Withdrew: The patient decided to withdraw via email1000
Withdrew: The patient was unresponsive to contact0004
Withdrew: The patient wished to participate no longer0100
Withdrew: Patient withdrew as they could no longer participate, as they had moved to canada0010

Outcome measures

PrimaryIncidence of Adverse Events Related to the Treatment

The primary outcome measure is the longer-term safety of treatment with AAV-CNGA3 or AAV-CNGB3, assessed by the absence of IMP-related adverse events.

Time frame:
5 Years
Reported as:
Count of participants · Participants
Incidence of Adverse Events Related to the Treatment
ParticipantsLow Dose AAV-CNGA3 or AAV-CNGB3Intermediate Dose AAV-CNGA3 or AAV-CNGB3Other Dose AAV-CNGA3 or AAV-CNGB3High Dose AAV-CNGA3 or AAV-CNGB3
Incidence of Adverse Events Related to the Treatment1200
SecondaryImprovements in Visual Function as Assessed by Visual Acuity at Month 12

Change from baseline to Month 12 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:
12 months
Reported as:
Mean · Number of ETDRS letters
Improvements in Visual Function as Assessed by Visual Acuity at Month 12
Number of ETDRS lettersLow Dose AAV-CNGA3 or AAV-CNGB3Intermediate Dose AAV-CNGA3 or AAV-CNGB3Other Dose AAV-CNGA3 or AAV-CNGB3High Dose AAV-CNGA3 or AAV-CNGB3
Improvements in Visual Function as Assessed by Visual Acuity at Month 12-0.6 (-3 to 1)0.2 (-5 to 4)3.5 (3 to 4)4.0 (-3 to 9)
SecondaryImprovements in Visual Function as Assessed by Visual Acuity at Month 60

Change from baseline to Month 60 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:
60 months
Reported as:
Mean · Number of ETDRS letters
Improvements in Visual Function as Assessed by Visual Acuity at Month 60
Number of ETDRS lettersLow Dose AAV-CNGA3 or AAV-CNGB3Intermediate Dose AAV-CNGA3 or AAV-CNGB3Other Dose AAV-CNGA3 or AAV-CNGB3High Dose AAV-CNGA3 or AAV-CNGB3
Improvements in Visual Function as Assessed by Visual Acuity at Month 603.3 (-4 to 7)0.1 (-4 to 3)—-0.3 (-7 to 7)
SecondaryImprovements in Retinal Function as Assessed by Static Perimetry at Month 12

Change from baseline to Month 12 in contrast sensitivity in the treated eye. The direction of improvement is an increase in sensitivity.

Time frame:
12 months
Reported as:
Mean · LogCS
Improvements in Retinal Function as Assessed by Static Perimetry at Month 12
LogCSLow Dose AAV-CNGA3 or AAV-CNGB3Intermediate Dose AAV-CNGA3 or AAV-CNGB3Other Dose AAV-CNGA3 or AAV-CNGB3High Dose AAV-CNGA3 or AAV-CNGB3
Improvements in Retinal Function as Assessed by Static Perimetry at Month 12-0.08 (-0.3 to 0.2)-0.17 (-0.4 to 0.1)0.12 (0.0 to 0.2)0.03 (-0.2 to 0.3)
SecondaryImprovements in Retinal Function as Assessed by Static Perimetry at Month 60

Change from baseline to Month 60 in contrast sensitivity in the treated eye. The direction of improvement is an increase in sensitivity.

Time frame:
60 months
Reported as:
Mean · LogCS
Improvements in Retinal Function as Assessed by Static Perimetry at Month 60
LogCSLow Dose AAV-CNGA3 or AAV-CNGB3Intermediate Dose AAV-CNGA3 or AAV-CNGB3Other Dose AAV-CNGA3 or AAV-CNGB3High Dose AAV-CNGA3 or AAV-CNGB3
Improvements in Retinal Function as Assessed by Static Perimetry at Month 60-0.19 (-1.0 to 0.4)-0.11 (-0.4 to 0.1)—-0.12 (-0.3 to 0.1)
SecondaryQuality of Life at Month 12 Measured by QoL Questionnaires in Children and Adolescents

Change from baseline to Month 12 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:
12 months
Reported as:
Mean · Units on a scale
Quality of Life at Month 12 Measured by QoL Questionnaires in Children and Adolescents
Units on a scaleLow Dose AAV-CNGA3 or AAV-CNGB3Intermediate Dose AAV-CNGA3 or AAV-CNGB3Other Dose AAV-CNGA3 or AAV-CNGB3High Dose AAV-CNGA3 or AAV-CNGB3
Quality of Life at Month 12 Measured by QoL Questionnaires in Children and Adolescents—4.3 (-6 to 19)9.5 (9 to 10)-12.0 (-12 to -12)
SecondaryQuality of Life at Month 60 Measured by QoL Questionnaires in Children and Adolescents

Change from baseline to Month 60 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:
60 months
Reported as:
Mean · Units on a scale
Quality of Life at Month 60 Measured by QoL Questionnaires in Children and Adolescents
Units on a scaleLow Dose AAV-CNGA3 or AAV-CNGB3Intermediate Dose AAV-CNGA3 or AAV-CNGB3Other Dose AAV-CNGA3 or AAV-CNGB3High Dose AAV-CNGA3 or AAV-CNGB3
Quality of Life at Month 60 Measured by QoL Questionnaires in Children and Adolescents—0.0 (-20 to 20)——
SecondaryQuality of Life at Month 12 Measured by QoL Questionnaires in Adults

Change from baseline to Month 12 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:
12 months
Reported as:
Mean · Units on a scale
Quality of Life at Month 12 Measured by QoL Questionnaires in Adults
Units on a scaleLow Dose AAV-CNGA3 or AAV-CNGB3Intermediate Dose AAV-CNGA3 or AAV-CNGB3Other Dose AAV-CNGA3 or AAV-CNGB3High Dose AAV-CNGA3 or AAV-CNGB3
Quality of Life at Month 12 Measured by QoL Questionnaires in Adults———0.5 (0 to 1)
SecondaryQuality of Life at Month 60 Measured by QoL Questionnaires in Adults

Change from baseline to Month 60 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:
60 months
Reported as:
Mean · Units on a scale
Quality of Life at Month 60 Measured by QoL Questionnaires in Adults
Units on a scaleLow Dose AAV-CNGA3 or AAV-CNGB3Intermediate Dose AAV-CNGA3 or AAV-CNGB3Other Dose AAV-CNGA3 or AAV-CNGB3High Dose AAV-CNGA3 or AAV-CNGB3
Quality of Life at Month 60 Measured by QoL Questionnaires in Adults0.0 (0 to 0)———

Adverse events

Collected over 5 years. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Low Dose AAV-CNGA3 or AAV-CNGB30/6 (0%)0/6 (0%)1/6 (16.7%)
Intermediate Dose AAV-CNGA3 or AAV-CNGB30/15 (0%)1/15 (6.7%)4/15 (26.7%)
Other Dose AAV-CNGA3 or AAV-CNGB30/3 (0%)0/3 (0%)3/3 (100%)
High Dose AAV-CNGA3 or AAV-CNGB30/10 (0%)1/10 (10%)2/10 (20%)
Total0/34 (0%)2/34 (5.9%)10/34 (29.4%)
Most frequent serious events
Most frequent serious events
EventLow Dose AAV-CNGA3 or AAV-CNGB3Intermediate Dose AAV-CNGA3 or AAV-CNGB3Other Dose AAV-CNGA3 or AAV-CNGB3High Dose AAV-CNGA3 or AAV-CNGB3Total
PneumothoraxRespiratory, thoracic and mediastinal disorders0/60/150/31/101/34
Retinal detachmentEye disorders0/61/150/30/101/34
Most frequent other events
Most frequent other events
EventLow Dose AAV-CNGA3 or AAV-CNGB3Intermediate Dose AAV-CNGA3 or AAV-CNGB3Other Dose AAV-CNGA3 or AAV-CNGB3High Dose AAV-CNGA3 or AAV-CNGB3Total
influenzaInfections and infestations0/61/152/30/103/34
NasopharyngitisInfections and infestations0/61/151/30/102/34
HeadacheNervous system disorders1/61/150/30/102/34
Vision blurredEye disorders0/62/150/31/103/34
Dry eyeEye disorders0/62/150/30/102/34
COVID-19Infections and infestations0/61/150/31/102/34

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Low Dose AAV-CNGA3 or AAV-CNGB3Intermediate Dose AAV-CNGA3 or AAV-CNGB3Other Dose AAV-CNGA3 or AAV-CNGB3High Dose AAV-CNGA3 or AAV-CNGB3Total
<=18 years3113522
Between 18 and 65 years340512
>=65 years00000
Sex: Female, Male
Sex: Female, Male(Participants)Low Dose AAV-CNGA3 or AAV-CNGB3Intermediate Dose AAV-CNGA3 or AAV-CNGB3Other Dose AAV-CNGA3 or AAV-CNGB3High Dose AAV-CNGA3 or AAV-CNGB3Total
Female3103420
Male350614
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Low Dose AAV-CNGA3 or AAV-CNGB3Intermediate Dose AAV-CNGA3 or AAV-CNGB3Other Dose AAV-CNGA3 or AAV-CNGB3High Dose AAV-CNGA3 or AAV-CNGB3Total
Hispanic or Latino00022
Not Hispanic or Latino6153832
Unknown or Not Reported00000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Low Dose AAV-CNGA3 or AAV-CNGB3Intermediate Dose AAV-CNGA3 or AAV-CNGB3Other Dose AAV-CNGA3 or AAV-CNGB3High Dose AAV-CNGA3 or AAV-CNGB3Total
American Indian or Alaska Native00000
Asian21025
Native Hawaiian or Other Pacific Islander00000
Black or African American00000
White4143829
More than one race00000
Unknown or Not Reported00000
Region of Enrollment
Region of Enrollment(participants)Low Dose AAV-CNGA3 or AAV-CNGB3Intermediate Dose AAV-CNGA3 or AAV-CNGB3Other Dose AAV-CNGA3 or AAV-CNGB3High Dose AAV-CNGA3 or AAV-CNGB3Total
United States01225
United Kingdom6141829
07

Study locations

2 sites
  • Kellogg Eye Center
    Ann Arbor, Michigan 48105, United States
  • Moorfields Eye Hospital NHS Foundation Trust
    London, United Kingdom
08

References and documents

Study documents

  • Study protocol · Dec 3, 2021
  • Statistical analysis plan · Aug 22, 2024

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT03278873
Lead sponsor
MeiraGTx UK II Ltd
Responsible party
Sponsor
First posted
Sep 12, 2017
Start date
Jun 29, 2017
Primary completion
Apr 4, 2024
Completion
Apr 4, 2024
Results posted
Jun 11, 2025
Last update
Jun 11, 2025

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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