UMIN-CTR Clinical Trial

Basic information
Public title	An investigator-initiated phase I/IIa trial of subretinal injection of DVC1-0401 as neuroprotective gene therapy for retinitis pigmentosa
Acronym	An investigator-initiated trial of DVC1-0401 as gene therapy for retinitis pigmentosa
Scientific Title	An investigator-initiated phase I/IIa trial of subretinal injection of DVC1-0401 as neuroprotective gene therapy for retinitis pigmentosa
Scientific Title:Acronym	An investigator-initiated trial of DVC1-0401 as gene therapy for retinitis pigmentosa
Region	Japan

Condition
Condition	Retinitis pigmentosa
Classification by specialty	Ophthalmology
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	For patients with retinitis pigmentosa accompanied with decreased central retinal sensitivity, 1) To examine safety of subretinal injection of DVC1-0401 2) To explore the inhibitory effect on declining visual function
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Explanatory
Developmental phase	Phase I,II

Assessment
Primary outcomes	Incidence of adverse events
Key secondary outcomes	1) Rate of change of the mean retinal sensitivity (central 12 points) : Primary outcome measure of efficiency 2) Rate of change of the mean retinal sensitivity (central 4 points) : Secondary outcome measure of efficiency-1 3) Rate of change of the visual acuity (logMAR converted value) : Secondary outcome measure of efficiency-2 4) Amount of hPEDF protein in the aqueous humor : Exploratory outcome measure

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	No treatment
Stratification	NO
Dynamic allocation	NO
Institution consideration	Institution is not considered as adjustment factor.
Blocking	NO
Concealment	No need to know

Intervention
No. of arms	3
Purpose of intervention	Treatment
Type of intervention	Gene
Interventions/Control_1	Subretinal injection of low-dose DCV1-0401 (Simian immunodeficiency virus vector expressing human pigment epithelium-derived factor (hPEDF))
Interventions/Control_2	Subretinal injection of medium-dose DCV1-0401
Interventions/Control_3	Subretinal injection of high-dose DCV1-0401
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	40 years-old <=
Age-upper limit	70 years-old >=
Gender	Male and Female
Key inclusion criteria	1) Subjects with retinitis pigmentosa diagnosed by two or more ophthalmic specialists 2) 40 years and above, and 70 years or younger 3) The mean retinal sensitivity measured by Humphrey perimeter (10-2 program) is less than 30 dB (central 4 points) 4) Interocular difference in visual acuity is less than or equal to 0.21 (logMAR converted value) 5) Interocular difference in visual field is less than or equal to twofold (Goldmann perimeter V-4e) 6) Interocular difference in the MD value measured by Humphrey perimeter (10-2 program) is less than or equal to 5 dB 7) Interocular difference in central retinal thickness measured by optical coherence tomography is less than or equal to 50 um 8) No interocular difference in the structure of outer retinal layer (ellipsoid zone) observed by optical coherence tomography 9) In case of subjects who are followed up over three years, interocular difference in the rate of change of visual acuity (logMAR converted value) and the MD value measured by Humphrey perimeter (10-2 program) is less than or equal to twofold 10) Difference in the mean retinal sensitivity measured in repeating tests using Humphrey perimeter (10-2 program) within 60 days before administration is binocularly less than or equal to 3 dB. If results from first and second tests don't fulfill the above criteria, the result from third test performed within 7 days from the second test is acceptable. 11) No significant pigmentation in ophthalmoscopic examination 12) Subjects who can give consent in writing by oneself (If subjects can not read the document because of reduction in visual function, both oral consent of the subject and signature of witness are necessary.)
Key exclusion criteria	1) HIV antibody-positive 2) Decimal visual acuities of both eyes are less than 0.1, or lateral or bilateral blindness 3) Cone-rod dystrophy 4) Interocular difference in the condition of lens 5) Co-existence of glaucoma or ocular hypertension (intraocular pressure is more than or equal to 22 mmHg) 6) Co-existence of uveitis or optic neuritis 7) Retinal or subretinal pathological change observed by fundus examination (including fluorescein fundus angiography, laser scanning fundus photography), that is independent of retinitis pigmentosa 8) Visual field measured by Goldmann perimeter V-4e is less than 10 degree at the center area of vision 9) Loss or massive structural irregularity of the layer of retinal pigment epithelium on OCT (optical coherence tomography) at the supposed site of administration 10) Having severe allergy or previous history 11) Receiving chronic hemodialysis therapy 12) Severe heart dysfunction or heart failure 13) Sever hepatic dysfunction or liver cirrhosis 14) Active inflammatory diseases 15) History of cerebral hemorrhage or infarction within 6 months before agreement 16) Hematopoietic disorders 17) Alcoholism and/or drug dependence 18) Female subjects with pregnant or doubt of pregnancy. Breast-feeding female. 19) Subjects who are diagnosed with cancer or suspected to have cancer. History of treatment of malignancies within 5 years. 20) Disapprove of birth control during at least 12 months after the administration 21) Administration of Helenien, Unoprostone, and/or Ca antagonist intended for treatment of eye disease within 30 days before agreement 22) Taking the antiviral drug at the registration 23) Plan of operation other than administration of the investigational drug during this clinical trial 24) Entry into other clinical trial and/or clinical study, or history of entry within 6 months before agreement 25) Others: Subjects who are judged to be inappropriate by principal investigator or subinvestigator
Target sample size	12

Research contact person
Name of lead principal investigator	1st name Yusuke Middle name Last name Murakami
Organization	Kyushu University Hospital
Division name	Department of Ophthalmology
Zip code	8128582
Address	3-1-1 Maidashi, Higashi-ku, Fukuoka, Japan
TEL	092-642-5648
Email	ymuraka3@pathol1.med.kyushu-u.ac.jp

Public contact
Name of contact person	1st name Yusuke Middle name Last name Murakami
Organization	Kyushu University Hospital
Division name	Department of Ophthalmology
Zip code	8128582
Address	3-1-1 Maidashi, Higashi-ku, Fukuoka, Japan
TEL	092-642-5648
Homepage URL
Email	ymuraka3@pathol1.med.kyushu-u.ac.jp

Sponsor
Institute	Kyushu University Hospital
Institute
Department

Funding Source
Organization	AMED
Organization
Division
Category of Funding Organization	Japanese Governmental office
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor	University of Miyazaki Hospital
Name of secondary funder(s)

IRB Contact (For public release)
Organization	Kyushu University Hospital IRB
Address	3-1-1, Maidashi, Higashi-ku
Tel	+81926425774
Email	bysirb@jimu.kyushu-u.ac.jp

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	九州大学病院（福岡県）、宮崎大学医学部附属病院（宮崎県）

Other administrative information
Date of disclosure of the study information	2018 Year 11 Month 01 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled	12
Results
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	No longer recruiting
Date of protocol fixation	2018 Year 07 Month 31 Day
Date of IRB	2018 Year 09 Month 21 Day
Anticipated trial start date	2019 Year 02 Month 14 Day
Last follow-up date	2023 Year 08 Month 31 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2018 Year 09 Month 10 Day
Last modified on	2022 Year 09 Month 06 Day

Link to view the page
URL(English)	https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000038854