Ignite Creation Date:
2025-12-24 @ 9:19 PM
Ignite Modification Date:
2025-12-25 @ 7:06 PM
Study NCT ID:
NCT03406104
Status:
COMPLETED
Last Update Posted:
2025-09-09
First Post:
2018-01-15
Is Possible Gene Therapy:
True
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
RESCUE and REVERSE Long-term Follow-up
Sponsor:
Organization:
Raw JSON
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Each participant was randomly assigned GS010 in either the right or left eye, the eye not assigned GS010 received the sham procedure. The eye assigned to the Sham received one single sham intravitreal (IVT) injection, which was performed by applying pressure to the eye at the location of a typical IVT injection procedure, using the blunt end of a syringe without a needle.\n\nThe same participants also received GS010 in the right or left eye, which did not receive the sham procedure, at the same study visit.', 'otherNumAtRisk': 62, 'deathsNumAtRisk': 62, 'otherNumAffected': 19, 'seriousNumAtRisk': 62, 'deathsNumAffected': 2, 'seriousNumAffected': 8}], 'otherEvents': [{'term': 'Cataract', 'stats': [{'groupId': 'EG000', 'numAtRisk': 62, 'numEvents': 13, 'numAffected': 6}], 'organSystem': 'Eye disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (19.0)'}, {'term': 'Gamma-Glutamyltransferase Increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 62, 'numEvents': 5, 'numAffected': 5}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (19.0)'}, {'term': 'Intraocular Pressure Increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 62, 'numEvents': 8, 'numAffected': 4}], 'organSystem': 'Eye disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (19.0)'}, {'term': 'Covid-19', 'stats': [{'groupId': 'EG000', 'numAtRisk': 62, 'numEvents': 4, 'numAffected': 4}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (19.0)'}], 'seriousEvents': [{'term': 'hip fracture', 'stats': [{'groupId': 'EG000', 'numAtRisk': 62, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (19.0)'}, {'term': 'humerus fracture', 'stats': [{'groupId': 'EG000', 'numAtRisk': 62, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (19.0)'}, {'term': 'cardiac arrest', 'stats': [{'groupId': 'EG000', 'numAtRisk': 62, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (19.0)'}, {'term': 'ileus', 'stats': [{'groupId': 'EG000', 'numAtRisk': 62, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (19.0)'}, {'term': 'lower limb fracture', 'stats': [{'groupId': 'EG000', 'numAtRisk': 62, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (19.0)'}, {'term': 'limb injury', 'stats': [{'groupId': 'EG000', 'numAtRisk': 62, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (19.0)'}, {'term': 'cerebral haemorrage', 'stats': [{'groupId': 'EG000', 'numAtRisk': 62, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (19.0)'}, {'term': 'glioblastoma multiforme', 'stats': [{'groupId': 'EG000', 'numAtRisk': 62, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Neoplasms benign, malignant and unspecified (incl cysts and polyps)', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (19.0)'}, {'term': 'appenditis perforated', 'stats': [{'groupId': 'EG000', 'numAtRisk': 62, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (19.0)'}, {'term': 'pneumonia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 62, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (19.0)'}, {'term': 'neoplasm progression', 'stats': [{'groupId': 'EG000', 'numAtRisk': 62, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Neoplasms benign, malignant and unspecified (incl cysts and polyps)', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (19.0)'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Ocular Adverse Events (AEs)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'OG000'}, {'value': '62', 'groupId': 'OG001'}]}, {'units': 'eyes', 'counts': [{'value': '62', 'groupId': 'OG000'}, {'value': '62', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'GS010 Treated Eyes', 'description': 'All eyes that received the study treatment, GS010. Each participant was randomly assigned GS010 in either the right or left eye. The eye assigned to GS010 received one single dose of GS010 (9E10 vg/eye) via an intravitreal (IVT) injection. The volume of the injected formula was 90 μL. The injection was performed in the vitreous humor under local anesthesia.\n\nThe same participants also received the sham procedure in the right or left eye, which was not assigned to receive GS010, at the same study visit.'}, {'id': 'OG001', 'title': 'Sham Treated Eyes', 'description': 'All eyes that received the Sham. Each participant was randomly assigned GS010 in either the right or left eye, the eye not assigned GS010 received the sham procedure. The eye assigned to the Sham received one single sham intravitreal (IVT) injection, which was performed by applying pressure to the eye at the location of a typical IVT injection procedure, using the blunt end of a syringe without a needle.\n\nThe same participants also received GS010 in the right or left eye, which did not receive the sham procedure, at the same study visit.'}], 'classes': [{'categories': [{'measurements': [{'value': '5', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'from year 2 to year 5 post treatment', 'description': 'Number of Eyes with Ocular Adverse events related to study treatment or study procedures as judged by the investigator reported from year 2 to year 5 post treatment', 'unitOfMeasure': 'eyes', 'reportingStatus': 'POSTED', 'typeUnitsAnalyzed': 'eyes', 'denomUnitsSelected': 'eyes'}, {'type': 'SECONDARY', 'title': 'Visual Acuity', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'OG000'}, {'value': '62', 'groupId': 'OG001'}]}, {'units': 'eyes', 'counts': [{'value': '62', 'groupId': 'OG000'}, {'value': '62', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'GS010 Treated Eyes', 'description': 'All eyes that received the study treatment, GS010. Each participant was randomly assigned GS010 in either the right or left eye. The eye assigned to GS010 received one single dose of GS010 (9E10 vg/eye) via an intravitreal (IVT) injection. The volume of the injected formula was 90 μL. The injection was performed in the vitreous humor under local anesthesia.\n\nThe same participants also received the sham procedure in the right or left eye, which was not assigned to receive GS010, at the same study visit.'}, {'id': 'OG001', 'title': 'Sham Treated Eyes', 'description': 'All eyes that received the Sham. Each participant was randomly assigned GS010 in either the right or left eye, the eye not assigned GS010 received the sham procedure. The eye assigned to the Sham received one single sham intravitreal (IVT) injection, which was performed by applying pressure to the eye at the location of a typical IVT injection procedure, using the blunt end of a syringe without a needle.\n\nThe same participants also received GS010 in the right or left eye, which did not receive the sham procedure, at the same study visit.'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.44', 'spread': '0.46', 'groupId': 'OG000'}, {'value': '-0.39', 'spread': '0.36', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Nadir to 5 Years post-treatment, Assessed at Baseline in RESCUE and REVERSE studies to year 5 post-treatment', 'description': 'Change from Nadir to 5 Years post-treatment, Assessed at Baseline in RESCUE and REVERSE studies to year 5 post-treatment, expressed in LogMAR.\n\nOn chart visual acuity: Visual acuity inferior or equal to LogMAR +1.6 Off chart visual acuity: Visual acuity superior to LogMar +1.7\n\nNormal vision LogMar: 0 and less than 0', 'unitOfMeasure': 'LogMar', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'typeUnitsAnalyzed': 'eyes', 'denomUnitsSelected': 'eyes', 'populationDescription': 'All efficacy analyses were conducted on the modified intent-to-treat population and additionally in subset populations, as appropriate.The modified intent-to-treat (mITT) population consisted of all subjects who received the IMP in RESCUE or REVERSE Phase III studies, consented to be enrolled in this LTFU study, and provided visual acuity data at Visit 2 (Year 2.5).'}, {'type': 'SECONDARY', 'title': 'Responder Analysis: Clinically Relevant Recovery', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'OG000'}, {'value': '62', 'groupId': 'OG001'}]}, {'units': 'eyes', 'counts': [{'value': '62', 'groupId': 'OG000'}, {'value': '62', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'GS010 Treated Eyes', 'description': 'All eyes that received the study treatment, GS010. Each participant was randomly assigned GS010 in either the right or left eye. The eye assigned to GS010 received one single dose of GS010 (9E10 vg/eye) via an intravitreal (IVT) injection. The volume of the injected formula was 90 μL. The injection was performed in the vitreous humor under local anesthesia.\n\nThe same participants also received the sham procedure in the right or left eye, which was not assigned to receive GS010, at the same study visit.'}, {'id': 'OG001', 'title': 'Sham Treated Eyes', 'description': 'All eyes that received the Sham. Each participant was randomly assigned GS010 in either the right or left eye, the eye not assigned GS010 received the sham procedure. The eye assigned to the Sham received one single sham intravitreal (IVT) injection, which was performed by applying pressure to the eye at the location of a typical IVT injection procedure, using the blunt end of a syringe without a needle.\n\nThe same participants also received GS010 in the right or left eye, which did not receive the sham procedure, at the same study visit.'}], 'classes': [{'categories': [{'measurements': [{'value': '60', 'groupId': 'OG000'}, {'value': '66', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Nadir to 5 Years post-treatment, Assessed at Baseline in RESCUE and REVERSE studies to year 5 post-treatment', 'description': 'CRR clinically relevant recovery from Nadir defined as i/ for eyes on chart at Nadir, an improvement of at least -0.2 LogMar from Nadir and ii/ for eyes off chart at Nadir eyes that became on chart.\n\nOff chart visual acuity expressed in LogMar: more than +1.7 On chart visual acuity expressed in LogMar: less than 1.6 Normal vision LogMar: 0 and less than 0', 'unitOfMeasure': 'percentage of eye', 'reportingStatus': 'POSTED', 'typeUnitsAnalyzed': 'eyes', 'denomUnitsSelected': 'eyes', 'populationDescription': 'All efficacy analyses were conducted on the modified intent-to-treat population and additionally in subset populations, as appropriate.The modified intent-to-treat (mITT) population consisted of all subjects who received the IMP in RESCUE or REVERSE Phase III studies, consented to be enrolled in this LTFU study, and provided visual acuity data at Visit 2 (Year 2.5).'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Eyes on Chart', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'OG000'}, {'value': '62', 'groupId': 'OG001'}]}, {'units': 'eyes', 'counts': [{'value': '62', 'groupId': 'OG000'}, {'value': '62', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'GS010-treated Eyes', 'description': 'Lenadogene nolparvovec Intravitreal ocular unilateral Injection Each participant will have one eye randomly selected to receive a single injection of GS010 and the other eye will receive a sham injection. GS010-treated Eyes: GS010 is a recombinant adeno-associated viral vector serotype 2 (rAAV2/2) containing the wild-type ND4 gene (rAAV2/2-ND4). Participants will receive a single dose of GS010 in one of their randomly selected eyes, via intravitreal injection containing 9E10 viral genomes in 90μL balanced salt solution (BSS) plus 0.001% Pluronic F68®.\n\nGS010: Lenadogene nolparvovec Intravitreal ocular unilateral Injection'}, {'id': 'OG001', 'title': 'Sham-treated Eyes', 'description': 'Sham Intravitreal ocular unilateral Injection Each participant will have one eye randomly selected to receive GS010 and the other eye will receive a sham injection. Eyes receiving sham injection will undergo the same preparatory procedures as eyes receiving GS010 injection, including pupillary dilation, topical anti-infection and topical anesthetic procedures. Sham intravitreal injection will be performed by applying pressure to the eye at the location of a typical intravitreal injection procedure using the blunt end of a syringe without a needle.\n\nSham Intravitreal Injection: Lenadogene nolparvovec Intravitreal ocular unilateral Injection'}], 'classes': [{'categories': [{'measurements': [{'value': '76', 'groupId': 'OG000'}, {'value': '79', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Year 5 post-treatment', 'description': 'Definition: Visual acuity inferior or equal to LogMAR +1.6 at 5 Years post treatment', 'unitOfMeasure': 'percentage of eyes', 'reportingStatus': 'POSTED', 'typeUnitsAnalyzed': 'eyes', 'denomUnitsSelected': 'eyes', 'populationDescription': 'All efficacy analyses were conducted on the modified intent-to-treat population and additionally in subset populations, as appropriate.The modified intent-to-treat (mITT) population consisted of all subjects who received the IMP in RESCUE or REVERSE Phase III studies, consented to be enrolled in this LTFU study, and provided visual acuity data at Visit 2 (Year 2.5).'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'All Patient Treated in RECUE and REVERSE Studies', 'description': 'all patients previously treated in RESCUE and REVERSE studies entered in this long term follow up study.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '62'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '55'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '7'}]}], 'dropWithdraws': [{'type': 'Lost to Follow-up', 'reasons': [{'groupId': 'FG000', 'numSubjects': '2'}]}, {'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '2'}]}, {'type': 'due to Covid patient did not want to travel', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}]}, {'type': 'Death', 'reasons': [{'groupId': 'FG000', 'numSubjects': '2'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Lenadogene Nolparvovec and Sham All Participants', 'description': 'All participants who were enrolled and received both study treatments, GS010 and Sham. All participants in the study received both GS010 and the sham procedure simultaneously. Participants were randomly assigned to receive GS010 in either the right or left eye. The same participants also received the sham procedure in the eye not assigned to GS010, at the same study visit.\n\nGS010: Either the right or left eye received one single dose of GS010 (9E10 vg/eye) via an intravitreal (IVT) injection. The volume of the injected formula was 90 µL. The injection was performed in the vitreous humor under local anesthesia.\n\nSham procedure: Either the right or left eye (the eye not randomly assigned to GS010) received the sham procedure. One single sham IVT injection was performed by applying pressure to the eye at the location of a typical IVT injection procedure, using the blunt end of a syringe without a needle.'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'BG000'}]}], 'categories': [{'title': '<=18 years', 'measurements': [{'value': '7', 'groupId': 'BG000'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '55', 'groupId': 'BG000'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '35.9', 'spread': '15.3', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'BG000'}]}], 'categories': [{'title': 'Female', 'measurements': [{'value': '13', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '49', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race and Ethnicity Not Collected', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants', 'populationDescription': 'Race and Ethnicity were not collected from any participant.'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '31', 'groupId': 'BG000'}]}]}, {'title': 'Italy', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '1', 'groupId': 'BG000'}]}]}, {'title': 'United Kingdom', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '5', 'groupId': 'BG000'}]}]}, {'title': 'France', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '16', 'groupId': 'BG000'}]}]}, {'title': 'Germany', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '9', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}, {'title': 'Best Corrected Visual Acuity', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '1.40', 'spread': '0.50', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'description': 'Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity scale.', 'unitOfMeasure': 'LogMAR', 'dispersionType': 'STANDARD_DEVIATION'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2018-09-17', 'size': 863034, 'label': 'Study Protocol', 'hasIcf': False, 'hasSap': False, 'filename': 'Prot_000.pdf', 'typeAbbrev': 'Prot', 'uploadDate': '2023-07-24T03:17', 'hasProtocol': True}, {'date': '2022-06-30', 'size': 561813, 'label': 'Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'SAP_001.pdf', 'typeAbbrev': 'SAP', 'uploadDate': '2023-07-24T03:20', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'intra patient comparaison'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 62}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2018-01-09', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-08', 'completionDateStruct': {'date': '2022-07-04', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-08-20', 'studyFirstSubmitDate': '2018-01-15', 'resultsFirstSubmitDate': '2023-09-26', 'studyFirstSubmitQcDate': '2018-01-15', 'lastUpdatePostDateStruct': {'date': '2025-09-09', 'type': 'ESTIMATED'}, 'resultsFirstSubmitQcDate': '2024-01-02', 'studyFirstPostDateStruct': {'date': '2018-01-23', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2024-01-25', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2022-07-04', 'type': 'ACTUAL'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Eyes on Chart', 'timeFrame': 'Year 5 post-treatment', 'description': 'Definition: Visual acuity inferior or equal to LogMAR +1.6 at 5 Years post treatment'}], 'primaryOutcomes': [{'measure': 'Ocular Adverse Events (AEs)', 'timeFrame': 'from year 2 to year 5 post treatment', 'description': 'Number of Eyes with Ocular Adverse events related to study treatment or study procedures as judged by the investigator reported from year 2 to year 5 post treatment'}], 'secondaryOutcomes': [{'measure': 'Visual Acuity', 'timeFrame': 'Nadir to 5 Years post-treatment, Assessed at Baseline in RESCUE and REVERSE studies to year 5 post-treatment', 'description': 'Change from Nadir to 5 Years post-treatment, Assessed at Baseline in RESCUE and REVERSE studies to year 5 post-treatment, expressed in LogMAR.\n\nOn chart visual acuity: Visual acuity inferior or equal to LogMAR +1.6 Off chart visual acuity: Visual acuity superior to LogMar +1.7\n\nNormal vision LogMar: 0 and less than 0'}, {'measure': 'Responder Analysis: Clinically Relevant Recovery', 'timeFrame': 'Nadir to 5 Years post-treatment, Assessed at Baseline in RESCUE and REVERSE studies to year 5 post-treatment', 'description': 'CRR clinically relevant recovery from Nadir defined as i/ for eyes on chart at Nadir, an improvement of at least -0.2 LogMar from Nadir and ii/ for eyes off chart at Nadir eyes that became on chart.\n\nOff chart visual acuity expressed in LogMar: more than +1.7 On chart visual acuity expressed in LogMar: less than 1.6 Normal vision LogMar: 0 and less than 0'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Heredity Optic Atrophy', 'Leber Hereditary Optic Atrophy', 'Leber Hereditary Optic Neuropathy', 'LHON', 'Eye Diseases', 'Hereditary Eye Diseases', 'Inborn Genetic Disease', 'Gene Therapy', 'Intravitreal Injections', 'Mitochondrial Disease', 'AAV2 Vectors', 'Nervous System Diseases', 'Neurodegenerative Disease', 'Heredodegenerative Disorders of the Nervous System'], 'conditions': ['Leber Hereditary Optic Neuropathy']}, 'referencesModule': {'references': [{'pmid': '39699886', 'type': 'DERIVED', 'citation': 'Yu-Wai-Man P, Newman NJ, Biousse V, Carelli V, Moster ML, Vignal-Clermont C, Klopstock T, Sadun AA, Sergott RC, Hage R, Degli Esposti S, La Morgia C, Priglinger C, Karanja R, Taiel M, Sahel JA; LHON Study Group. Five-Year Outcomes of Lenadogene Nolparvovec Gene Therapy in Leber Hereditary Optic Neuropathy. JAMA Ophthalmol. 2025 Feb 1;143(2):99-108. doi: 10.1001/jamaophthalmol.2024.5375.'}, {'pmid': '36449262', 'type': 'DERIVED', 'citation': 'Carelli V, Newman NJ, Yu-Wai-Man P, Biousse V, Moster ML, Subramanian PS, Vignal-Clermont C, Wang AG, Donahue SP, Leroy BP, Sergott RC, Klopstock T, Sadun AA, Rebolleda Fernandez G, Chwalisz BK, Banik R, Girmens JF, La Morgia C, DeBusk AA, Jurkute N, Priglinger C, Karanjia R, Josse C, Salzmann J, Montestruc F, Roux M, Taiel M, Sahel JA; the LHON Study Group. Indirect Comparison of Lenadogene Nolparvovec Gene Therapy Versus Natural History in Patients with Leber Hereditary Optic Neuropathy Carrying the m.11778G>A MT-ND4 Mutation. Ophthalmol Ther. 2023 Feb;12(1):401-429. doi: 10.1007/s40123-022-00611-x. Epub 2022 Nov 30.'}, {'pmid': '34108929', 'type': 'DERIVED', 'citation': 'Newman NJ, Yu-Wai-Man P, Carelli V, Biousse V, Moster ML, Vignal-Clermont C, Sergott RC, Klopstock T, Sadun AA, Girmens JF, La Morgia C, DeBusk AA, Jurkute N, Priglinger C, Karanjia R, Josse C, Salzmann J, Montestruc F, Roux M, Taiel M, Sahel JA. Intravitreal Gene Therapy vs. Natural History in Patients With Leber Hereditary Optic Neuropathy Carrying the m.11778G>A ND4 Mutation: Systematic Review and Indirect Comparison. Front Neurol. 2021 May 24;12:662838. doi: 10.3389/fneur.2021.662838. eCollection 2021.'}]}, 'descriptionModule': {'briefSummary': 'The goal of this clinical trial is to assess the long-term safety and efficacy of GS010, a gene therapy, and assess the quality of life in subjects with LHON due to the G11778A ND4 mitochondrial mutation and who were treated in the Rescue or Reverse studies.', 'detailedDescription': 'Seven investigational centers from the RESCUE and REVERSE studies also participated in the RESTORE study, located in the European union and in the USA.\n\nPrimary objectives: to assess the long term safety of intravitreal injection up to 5 years of post treatment in subjects who were treated in the RESCUE or REVERSE studies.\n\nSecondary objectives: (1) to assess the long-term efficacy of intravitreal GS010 administration up to 5 years post-treatment in subjects who were treated in the RESCUE or REVERSE studies; and (2) to assess the quality of life (QoL) in subjects who were treated with GS010 in the RESCUE or REVERSE studies for up to 5 years post-treatment.\n\nMethodology: This was a Phase III prospective long-term follow-up (LTFU) clinical study of subjects previously treated with GS010 and Sham during 2 Phase III studies-RESCUE and REVERSE. The LTFU study followed subjects for an additional 3 years, for a total of 5 years post-injection. The LTFU study included 5 visits at 2, 2.5, 3, 4, and 5 years after the investigational medicinal product (IMP) injection. Safety, efficacy, and QoL variables were assessed during each of the 5 LTFU visits, and descriptive summaries and statistical testing were used for the analysis of the data.\n\nThis report presents the final analysis of results at Year 5 after treatment administration in RESCUE and REVERSE.\n\nNumber of analysed subjects: all subjects completing RECUE and REVERSE studies who provided consent for the RESTORE study: 62 subjects.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'minimumAge': '15 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria\n\n* Subject was treated with GS010 IVT injection in either of the RESCUE or REVERSE Phase III clinical studies\n* Subject of legal consent age has provided informed consent; subjects that are not of legal consent age have undergone their country-approved clinical trial enrollment consent process\n\nExclusion Criteria\n\n* Subject is unwilling or unable to comply with the protocol requirements\n* Subject has any medical or psychological condition that, in the opinion of the Investigator, may compromise his or her safe participation in the study\n* Subject is taking or intending to take idebenone during the long-term follow-up study period'}, 'identificationModule': {'nctId': 'NCT03406104', 'acronym': 'RESTORE', 'briefTitle': 'RESCUE and REVERSE Long-term Follow-up', 'organization': {'class': 'INDUSTRY', 'fullName': 'GenSight Biologics'}, 'officialTitle': 'Long-term Follow-up of ND4 LHON Subjects Treated With GS010 Ocular Gene Therapy in the RESCUE or REVERSE Phase III Clinical Trials (RESTORE)', 'orgStudyIdInfo': {'id': 'GS-LHON-CLIN-06'}, 'secondaryIdInfos': [{'id': '2017-002153-11', 'type': 'EUDRACT_NUMBER'}, {'id': 'NCT02652767 RESCUE', 'type': 'OTHER', 'domain': 'clin.trial.gov'}, {'id': 'NCT02652780 REVERSE', 'type': 'OTHER', 'domain': 'clin.trial.gov'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'GS010-treated Eyes', 'description': 'Lenadogene nolparvovec Intravitreal ocular unilateral Injection Each participant will have one eye randomly selected to receive a single injection of GS010 and the other eye will receive a sham injection. GS010-treated Eyes: GS010 is a recombinant adeno-associated viral vector serotype 2 (rAAV2/2) containing the wild-type ND4 gene (rAAV2/2-ND4). Participants will receive a single dose of GS010 in one of their randomly selected eyes, via intravitreal injection containing 9E10 viral genomes in 90μL balanced salt solution (BSS) plus 0.001% Pluronic F68®.', 'interventionNames': ['Genetic: GS010']}, {'type': 'SHAM_COMPARATOR', 'label': 'Sham-treated Eyes', 'description': 'Sham Intravitreal ocular unilateral Injection Each participant will have one eye randomly selected to receive GS010 and the other eye will receive a sham injection. Eyes receiving sham injection will undergo the same preparatory procedures as eyes receiving GS010 injection, including pupillary dilation, topical anti-infection and topical anesthetic procedures. Sham intravitreal injection will be performed by applying pressure to the eye at the location of a typical intravitreal injection procedure using the blunt end of a syringe without a needle.', 'interventionNames': ['Other: Sham Intravitreal Injection']}], 'interventions': [{'name': 'GS010', 'type': 'GENETIC', 'otherNames': ['Lenadogene Nolparvovec'], 'description': 'Lenadogene nolparvovec Intravitreal ocular unilateral Injection', 'armGroupLabels': ['GS010-treated Eyes']}, {'name': 'Sham Intravitreal Injection', 'type': 'OTHER', 'description': 'Lenadogene nolparvovec Intravitreal ocular unilateral Injection', 'armGroupLabels': ['Sham-treated Eyes']}]}, 'contactsLocationsModule': {'locations': [{'zip': '91105', 'city': 'Pasadena', 'state': 'California', 'country': 'United States', 'facility': 'Doheny Eye Center UCLA', 'geoPoint': {'lat': 34.14778, 'lon': -118.14452}}, {'zip': '30322', 'city': 'Atlanta', 'state': 'Georgia', 'country': 'United States', 'facility': 'Emory University Hospital', 'geoPoint': {'lat': 33.749, 'lon': -84.38798}}, {'zip': '19107', 'city': 'Philadelphia', 'state': 'Pennsylvania', 'country': 'United States', 'facility': 'Wills Eye Institute', 'geoPoint': {'lat': 39.95238, 'lon': -75.16362}}, {'zip': '75012', 'city': 'Paris', 'country': 'France', 'facility': 'CHNO Les Quinze Vingts', 'geoPoint': {'lat': 48.85341, 'lon': 2.3488}}, {'zip': '80336', 'city': 'Munich', 'country': 'Germany', 'facility': 'LMU Klinikum der Universität München / Friedrich-Baur-Institut', 'geoPoint': {'lat': 48.13743, 'lon': 11.57549}}, {'zip': '40139', 'city': 'Bologna', 'country': 'Italy', 'facility': 'Ospedale Bellaria', 'geoPoint': {'lat': 44.49381, 'lon': 11.33875}}, {'zip': 'EC1V 2PD', 'city': 'London', 'state': 'Greater London', 'country': 'United Kingdom', 'facility': 'Moorfields Eye Hospital', 'geoPoint': {'lat': 51.50853, 'lon': -0.12574}}], 'overallOfficials': [{'name': 'Nancy Newman, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Emory University Hospital Atlanta, Georgia, United States, 30322'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'GenSight Biologics', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}