Klinikai vizsgálatok Nct

Summary
EudraCT Number:2020-002873-88
Sponsor's Protocol Code Number:MGT-RPGR-021
National Competent Authority:Denmark - DHMA
Clinical Trial Type:EEA CTA
Trial Status:Ongoing
Date on which this record was first entered in the EudraCT database:2021-11-08
Trial results
Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL
A. Protocol Information
A.1Member State ConcernedDenmark - DHMA
A.2EudraCT number2020-002873-88
A.3Full title of the trial
Phase 3 Randomized, Controlled Study of AAV5-hRKp.RPGR for the Treatment of X-linked Retinitis Pigmentosa Associated with Variants in the RPGR gene
A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
Gene Therapy Trial for Patients with Retinitis Pigmentosa (progressive reduction in vision) due to a gene defect on Chromosome X.
A.3.2Name or abbreviated title of the trial where available
Gene Therapy Trial for Patients with Retinitis Pigmentosa: RPGR
A.4.1Sponsor's protocol code numberMGT-RPGR-021
A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04671433
A.7Trial is part of a Paediatric Investigation Plan Yes
A.8EMA Decision number of Paediatric Investigation PlanP/125/2021
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorJanssen-Cilag International NV
B.1.3.4CountryBelgium
B.3.1 and B.3.2Status of the sponsorCommercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing supportJanssen Research & Development, LLC
B.4.2CountryUnited States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationJanssen-Cilag International NV
B.5.2Functional name of contact pointClinical Registry Group
B.5.3 Address:
B.5.3.1Street AddressArchimedesweg 29
B.5.3.2Town/ cityLeiden
B.5.3.3Post code2333 CM
B.5.3.4CountryNetherlands
B.5.4Telephone number+3171 52421 66
B.5.5Fax number+3171 52421 10
B.5.6E-mailClinicalTrialsEU@its.jnj.com
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation No
D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
D.2.5.1Orphan drug designation numberEU/3/16/1715
D.3 Description of the IMP
D.3.1Product nameBotaretigene Sparoparvovec
D.3.2Product code AAV5-hRKp.RPGR
D.3.4Pharmaceutical form Solution for injection
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPSubretinal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNbotaretigene sparoparvovec
D.3.9.3Other descriptive nameAAV5-HRKP.RPGR
D.3.9.4EV Substance CodeSUB188497
D.3.10 Strength
D.3.10.1Concentration unit vector genomes (vg)/mL
D.3.10.2Concentration typeequal
D.3.10.3Concentration number4e11
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin No
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) Yes
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product Yes
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Yes
D.3.11.3.5.1CAT classification and reference numberGene therapy medicinal product; EMA/CAT/14302/2020EMA/CAT/14302/2020
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product Yes
D.3.11.10Medicinal product containing genetically modified organisms Yes
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.IMP: 2
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation No
D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
D.2.5.1Orphan drug designation numberEU/3/16/1715
D.3 Description of the IMP
D.3.1Product nameBotaretigene Sparoparvovec
D.3.2Product code AAV5-hRKp.RPGR
D.3.4Pharmaceutical form Solution for injection
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPSubretinal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNbotaretigene sparoparvovec
D.3.9.3Other descriptive nameAAV5-HRKP.RPGR
D.3.9.4EV Substance CodeSUB188497
D.3.10 Strength
D.3.10.1Concentration unit vector genomes (vg)/mL
D.3.10.2Concentration typeequal
D.3.10.3Concentration number2e11
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin No
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) Yes
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product Yes
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Yes
D.3.11.3.5.1CAT classification and reference numberGene therapy medicinal product; EMA/CAT/14302/2020
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product Yes
D.3.11.10Medicinal product containing genetically modified organisms Yes
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.8 Information on Placebo
E. General Information on the Trial
E.1 Medical condition or disease under investigation
E.1.1Medical condition(s) being investigated
X-Linked Retinitis Pigmentosa caused by mutations in the RPGR gene
E.1.1.1Medical condition in easily understood language
Progressive reduction in vision, starting with night blindness and progressing to visual field constriction, caused by mutations on Chromosome X (RPGR gene).
E.1.1.2Therapeutic area Diseases [C] - Eye Diseases [C11]
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 20.0
E.1.2Level PT
E.1.2Classification code 10038914
E.1.2Term Retinitis pigmentosa
E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
E.1.3Condition being studied is a rare disease Yes
E.2 Objective of the trial
E.2.1Main objective of the trial
To assess the effect of bilateral treatment with AAV5-hRKp.RPGR on functional vision as measured by vision-guided mobility assessment (VMA)
E.2.2Secondary objectives of the trial
To assess changes after treatment administration in retinal function, functional vision, visual function and to assess the safety and tolerability of bilateral subretinal delivery of AAV5-hRKp.RPGR
E.2.3Trial contains a sub-study No
E.3Principal inclusion criteria
1. Male or female.
2. 3 years of age or older.
3. Has XLRP (generalized rod-cone dystrophy) confirmed by a retinal specialist and has a predicted disease-causing sequence variant in RPGR confirmed by a sponsor-approved laboratory.


E.4Principal exclusion criteria
1. Has had ocular surgery within 3 months prior to screening or is anticipated to require ocular surgery within 6 months after the study intervention administration.
2. Any investigational ocular treatment or any other ocular treatment that could confound the interpretation of the efficacy results or affect participant compliance with the visit schedule.
3. Has undergone prior retinal surgery involving the macula, vitrectomy, macular laser photocoagulation, external-beam radiation therapy, transpupillary thermotherapy, glaucoma filtration surgery or corneal surgery (except cataract surgery).
4. History of an ocular implant, with the exception of an intraocular lens.

E.5 End points
E.5.1Primary end point(s)
Change from baseline to Week 52 in binocular VMA.
E.5.1.1Timepoint(s) of evaluation of this end point
Baseline to week 52
E.5.2Secondary end point(s)
•Retinal Function assessed by
- Mean retinal sensitivity within the central 10 degrees excluding
scotoma (MRS10) in static perimetry at Week 52
- Pointwise responder in full visual field at Week 52
- Pointwise responder in the central 30 degrees visual field at Week 52
- Mean retinal sensitivity within the full visual field excluding scotoma

•Functional Vision assessed by
- Vision-guided mobility response in the "worse-seeing eye" as assessed
by VMA at Week 52
- Low Luminance Questionnaire (LLQ) in patient reported outcome –
Extreme lighting domain score at Week 52

•Visual Function assessed by
- Low luminance visual acuity by Early Treatment Diabetic Retinopathy
Study (ETDRS) chart letter score in binocular assessment at Week 52
- Best corrected visual acuity (BCVA) by Early Treatment Diabetic
Retinopathy Study (ETDRS) chart letter score in binocular assessment at
Week 52

• Adverse Events

• Laboratory assessments
E.5.2.1Timepoint(s) of evaluation of this end point
Baseline to week 52
E.6 and E.7 Scope of the trial
E.6Scope of the trial
E.6.1Diagnosis No
E.6.2Prophylaxis No
E.6.3Therapy Yes
E.6.4Safety Yes
E.6.5Efficacy Yes
E.6.6Pharmacokinetic No
E.6.7Pharmacodynamic No
E.6.8Bioequivalence No
E.6.9Dose response Yes
E.6.10Pharmacogenetic No
E.6.11Pharmacogenomic No
E.6.12Pharmacoeconomic No
E.6.13Others No
E.7Trial type and phase
E.7.1Human pharmacology (Phase I) No
E.7.1.1First administration to humans No
E.7.1.2Bioequivalence study No
E.7.1.3Other No
E.7.1.3.1Other trial type description
E.7.2Therapeutic exploratory (Phase II) No
E.7.3Therapeutic confirmatory (Phase III) Yes
E.7.4Therapeutic use (Phase IV) No
E.8 Design of the trial
E.8.1Controlled Yes
E.8.1.1Randomised Yes
E.8.1.2Open No
E.8.1.3Single blind No
E.8.1.4Double blind No
E.8.1.5Parallel group Yes
E.8.1.6Cross over No
E.8.1.7Other Yes
E.8.1.7.1Other trial design description
Vision assessors to be masked to treatment assignment
E.8.2 Comparator of controlled trial
E.8.2.1Other medicinal product(s) No
E.8.2.2Placebo No
E.8.2.3Other Yes
E.8.2.3.1Comparator description
No treatment (Deferred treatment for control group).
E.8.2.4Number of treatment arms in the trial2
E.8.3 The trial involves single site in the Member State concerned Yes
E.8.4 The trial involves multiple sites in the Member State concerned No
E.8.5The trial involves multiple Member States Yes
E.8.5.1Number of sites anticipated in the EEA20
E.8.6 Trial involving sites outside the EEA
E.8.6.1Trial being conducted both within and outside the EEA Yes
E.8.6.2Trial being conducted completely outside of the EEA No
E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
Switzerland
Canada
Israel
United Kingdom
United States
Belgium
Denmark
France
Germany
Ireland
Italy
Netherlands
Spain
E.8.7Trial has a data monitoring committee Yes
E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
LVLS
E.8.9 Initial estimate of the duration of the trial
E.8.9.1In the Member State concerned years1
E.8.9.1In the Member State concerned months9
E.8.9.1In the Member State concerned days0
E.8.9.2In all countries concerned by the trial years1
E.8.9.2In all countries concerned by the trial months9
E.8.9.2In all countries concerned by the trial days0
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 Yes
F.1.1Number of subjects for this age range: 6
F.1.1.1In Utero No
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
F.1.1.3Newborns (0-27 days) No
F.1.1.4Infants and toddlers (28 days-23 months) No
F.1.1.5Children (2-11years) Yes
F.1.1.5.1Number of subjects for this age range: 3
F.1.1.6Adolescents (12-17 years) Yes
F.1.1.6.1Number of subjects for this age range: 3
F.1.2Adults (18-64 years) Yes
F.1.2.1Number of subjects for this age range: 90
F.1.3Elderly (>=65 years) No
F.2 Gender
F.2.1Female Yes
F.2.2Male Yes
F.3 Group of trial subjects
F.3.1Healthy volunteers No
F.3.2Patients Yes
F.3.3Specific vulnerable populations Yes
F.3.3.1Women of childbearing potential not using contraception No
F.3.3.2Women of child-bearing potential using contraception Yes
F.3.3.3Pregnant women No
F.3.3.4Nursing women No
F.3.3.5Emergency situation No
F.3.3.6Subjects incapable of giving consent personally Yes
F.3.3.6.1Details of subjects incapable of giving consent
Children 3 years and older
F.3.3.7Others No
F.4 Planned number of subjects to be included
F.4.1In the member state2
F.4.2 For a multinational trial
F.4.2.1In the EEA 23
F.4.2.2In the whole clinical trial 96
F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
The intervention is a one-time treatment. Subjects randomised to immediate treatment will receive bilateral treatment during the study, no further treatment will be provided. Subjects receiving treatment will be followed for 1 year and an additional 4 years as part of the follow-up study. Subjects randomised to deferred treatment will be offered bilateral treatment as part of the MGT-RPGR-022 study and followed for 5 years. No further treatment will be offered after subjects end participation.
G. Investigator Networks to be involved in the Trial
N. Review by the Competent Authority or Ethics Committee in the country concerned
N.Competent Authority Decision Authorised
N.Date of Competent Authority Decision2022-03-01
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2021-01-27
P. End of Trial
P.End of Trial StatusOngoing

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