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Safety and Tolerability of KH631 Gene Therapy in Subjects With Neovascular Age-related Macular Degeneration (nAMD)

Primary Purpose

Age-Related Macular Degeneration

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
KH631
Sponsored by
Chengdu Origen Biotechnology Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Age-Related Macular Degeneration

Eligibility Criteria

50 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 1.Are willing and able to sign the study written informed consent form (ICF); 2. Men and women ≥ 50 and ≤85 years of age, diagnosed with nAMD at the Screening visit; 3. Subjects must be under active anti-VEGF treatment for nAMD and received a minimum of 3 injections within 6 months prior to screening; 4. Response to anti-VEGF therapy(Response is defined as reduction in CRT≥50μm or at least 30% reduction in fluid by OCT compared to disease at the worst); 5. BCVA between ≤20/63 and ≥20/400(≤63 and ≥19 Early Treatment Diabetic Retinopathy Study [ETDRS] letters) for the first patient in each cohort followed by BCVA between ≤20/40 and ≥20/400(≤73 and ≥19 ETDRS letters) for the rest of the cohort; 6. Must be pseudophakic(at least 3 months after intraocular lens implantation) in the study eye; 7.Female subjects must have been postmenopausal for at least 1 year. Exclusion Criteria: 1.Any other cause of CNV, including pathologic myopia, etc, or other diseases except nAMD have an influence on the test of macular or affect the central visual acuity; 2.Presence of an implant, refractive media opacity affects fundus examination or narrow pupil of the study eye; 3.Active or history of retinal detachment in the study eye; 4.Uncontrolled glaucoma or ocular hypertension; 5.Have taken the drug known to have retinal toxicity; 6.History of intraocular surgery; 7.Uncontrolled hypertension despite medication at the screening visit.

Sites / Locations

  • Beijing Tongren Hospital, Capital Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

KH631 Dose 1

KH631 Dose 2

KH631 Dose 3

KH631 Dose 4

KH631 Dose 5

Arm Description

dose1:Administered by Subretinal injection. Dosage form: injection solution. Dose: 200uL. Frequency of administration: one time injection.

dose2:Administered by Subretinal injection. Dosage form: injection solution. Dose: 200uL. Frequency of administration: one time injection.

dose3:Administered by Subretinal injection. Dosage form: injection solution. Dose: 200uL. Frequency of administration: one time injection.

dose4:Administered by Subretinal injection. Dosage form: injection solution. Dose: 200uL. Frequency of administration: one time injection.

dose5:Administered by Subretinal injection. Dosage form: injection solution. Dose: 200uL. Frequency of administration: one time injection.

Outcomes

Primary Outcome Measures

Safety
incidence of AEs and SAEs
Change in best corrected visual acuity
BCVA

Secondary Outcome Measures

Safety
incidence of AEs and SAEs
Change in best corrected visual acuity
BCVA
Change in central retinal thickness
CRT
Change in area of retinal leakage
Leakage measured by FFA
Rescue injections
Mean number of rescue injections

Full Information

First Posted
December 21, 2022
Last Updated
September 22, 2023
Sponsor
Chengdu Origen Biotechnology Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05672121
Brief Title
Safety and Tolerability of KH631 Gene Therapy in Subjects With Neovascular Age-related Macular Degeneration (nAMD)
Official Title
A Phase I/II, Open-label, Multiple-cohort, Dose-escalation Study to Evaluate the Safety and Tolerability of KH631 Gene Therapy in Subjects With Neovascular Age-related Macular Degeneration (nAMD)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 6, 2023 (Actual)
Primary Completion Date
December 28, 2026 (Anticipated)
Study Completion Date
December 28, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Chengdu Origen Biotechnology Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
KH631 is a adeno-associated virus (AAV) vector-based gene therapy for subretinal injection. The long-term, stable therapeutic protein after one time injection for nAMD could potentially reduce the treatment burden and maintain vision.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Age-Related Macular Degeneration

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
42 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
KH631 Dose 1
Arm Type
Experimental
Arm Description
dose1:Administered by Subretinal injection. Dosage form: injection solution. Dose: 200uL. Frequency of administration: one time injection.
Arm Title
KH631 Dose 2
Arm Type
Experimental
Arm Description
dose2:Administered by Subretinal injection. Dosage form: injection solution. Dose: 200uL. Frequency of administration: one time injection.
Arm Title
KH631 Dose 3
Arm Type
Experimental
Arm Description
dose3:Administered by Subretinal injection. Dosage form: injection solution. Dose: 200uL. Frequency of administration: one time injection.
Arm Title
KH631 Dose 4
Arm Type
Experimental
Arm Description
dose4:Administered by Subretinal injection. Dosage form: injection solution. Dose: 200uL. Frequency of administration: one time injection.
Arm Title
KH631 Dose 5
Arm Type
Experimental
Arm Description
dose5:Administered by Subretinal injection. Dosage form: injection solution. Dose: 200uL. Frequency of administration: one time injection.
Intervention Type
Drug
Intervention Name(s)
KH631
Intervention Description
KH631: AAV vector containing a coding sequence for an anti-VEGF protein
Primary Outcome Measure Information:
Title
Safety
Description
incidence of AEs and SAEs
Time Frame
24 weeks
Title
Change in best corrected visual acuity
Description
BCVA
Time Frame
52 weeks
Secondary Outcome Measure Information:
Title
Safety
Description
incidence of AEs and SAEs
Time Frame
104 weeks
Title
Change in best corrected visual acuity
Description
BCVA
Time Frame
104 weeks
Title
Change in central retinal thickness
Description
CRT
Time Frame
104 weeks
Title
Change in area of retinal leakage
Description
Leakage measured by FFA
Time Frame
104 weeks
Title
Rescue injections
Description
Mean number of rescue injections
Time Frame
104 weeks
Other Pre-specified Outcome Measures:
Title
KH631 protein in aqueous fluid and blood
Description
Exploratory
Time Frame
104 weeks
Title
VEGF-A in aqueous fluid and blood
Description
Exploratory
Time Frame
104 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 1.Are willing and able to sign the study written informed consent form (ICF); 2. Men and women ≥ 50 and ≤85 years of age, diagnosed with nAMD at the Screening visit; 3. Subjects must be under active anti-VEGF treatment for nAMD and received a minimum of 3 injections within 6 months prior to screening; 4. Response to anti-VEGF therapy(Response is defined as reduction in CRT≥50μm or at least 30% reduction in fluid by OCT compared to disease at the worst); 5. BCVA between ≤20/63 and ≥20/400(≤63 and ≥19 Early Treatment Diabetic Retinopathy Study [ETDRS] letters) for the first patient in each cohort followed by BCVA between ≤20/40 and ≥20/400(≤73 and ≥19 ETDRS letters) for the rest of the cohort; 6. Must be pseudophakic(at least 3 months after intraocular lens implantation) in the study eye; 7.Female subjects must have been postmenopausal for at least 1 year. Exclusion Criteria: 1.Any other cause of CNV, including pathologic myopia, etc, or other diseases except nAMD have an influence on the test of macular or affect the central visual acuity; 2.Presence of an implant, refractive media opacity affects fundus examination or narrow pupil of the study eye; 3.Active or history of retinal detachment in the study eye; 4.Uncontrolled glaucoma or ocular hypertension; 5.Have taken the drug known to have retinal toxicity; 6.History of intraocular surgery; 7.Uncontrolled hypertension despite medication at the screening visit.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Qiang Zheng
Phone
86 13880331037
Email
zhengqiang@cnkh.com
First Name & Middle Initial & Last Name or Official Title & Degree
Ting Hu
Phone
86 13880999215
Email
huting@cnkh.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wenbin Wei, PhD
Organizational Affiliation
Beijing Tongren Hospital Affiliated to Capital Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beijing Tongren Hospital, Capital Medical University
City
Beijing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wenbin Wei, PhD
Phone
86 13701255115
Email
tr_weiwenbin@163.com

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Safety and Tolerability of KH631 Gene Therapy in Subjects With Neovascular Age-related Macular Degeneration (nAMD)

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