Treatment of Central Retinal Vein Occlusion Using Stem Cells Study

NCT03981549 | Completed Phase 1 Results DMC FDA Drug

• 3 other identifiers: TRUST1UG1EY026876-01A11UG1EY028517-01
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates whether intravitreal autologous CD34+ stem cell therapy is safe, feasible and potentially beneficial in eyes with vision loss from central retinal vein occlusion (CRVO). Half of the participants will receive immediate cellular therapy followed by sham therapy 6 months later, while the other half will receive immediate sham therapy followed by cellular therapy 6 months later. Participants will be followed for a total of 1 year.

Conditions

Central Retinal Vein Occlusion

Keywords

Central Retinal Vein Occlusion; Retinal Vein Occlusion; Retinal Diseases; Eye Diseases; CD34+ Stem Cell Therapy; Autologous Bone Marrow Stem Cells; Stem Cells

Outcome Measures

Primary Outcomes (2)

• Incidence and Severity of Ocular and Systemic Adverse Events

  The primary safety outcome will be assessed at month 6. Adverse events (AE) that occur during the first 6 months of the trial will be broken down by whether the AE occurred following the sham or cellular treatment to assess differences in the adverse event experience between the cellular and sham therapies.

  Months 0 to 6

• Feasibility of the Stem Cell Therapy

  Number of CD34+ cells isolated from the bone marrow aspirate and number of cells injected into the eye

  Day 0 and Day 182

Secondary Outcomes (20)

• Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity Letter Score

  Months 0 to 6

• Change in % Reduced Sensitivity

  Months 0 to 6

• Change in Average Threshold

  Months 0 to 6

• Change in Percent Normal Amplitude for ERG+OP (Oscillatory Potential) A-wave Under Scotopic Conditions

  Months 0 to 6

• Change in Percent Normal Amplitude for ERG+OP B-wave Under Scotopic Conditions

  Months 0 to 6

Study Arms (2)

Immediate Cellular Therapy / Deferred Sham Therapy

ACTIVE COMPARATOR

At baseline: Bone marrow aspiration followed by intravitreal injection of CD34+ cells. At 6 months: Sham bone marrow aspiration and sham intravitreal injection.

Biological: Autologous Bone Marrow CD34+ Stem Cells; Biological: Sham Therapy

Immediate Sham Therapy / Deferred Cellular Therapy

SHAM COMPARATOR

At baseline: Sham bone marrow aspiration followed by sham intravitreal injection. At 6 months: Bone marrow aspiration followed by intravitreal injection of CD34+ cells.

Biological: Autologous Bone Marrow CD34+ Stem Cells; Biological: Sham Therapy

Interventions

Autologous Bone Marrow CD34+ Stem Cells BIOLOGICAL

Single intravitreal injection of autologous bone marrow CD34+ stem cells. The number of cells to be injected per eye will range from 800,000 to 10 million, depending on the yield of the bone marrow aspiration and the isolation procedure.

Immediate Cellular Therapy / Deferred Sham Therapy; Immediate Sham Therapy / Deferred Cellular Therapy

Sham Therapy BIOLOGICAL

Sham bone marrow aspiration procedure that penetrates the skin, but does not penetrate the bone followed by sham intravitreal injection without penetration of the eye

Immediate Cellular Therapy / Deferred Sham Therapy; Immediate Sham Therapy / Deferred Cellular Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Clinical diagnosis of central retinal vein occlusion (CRVO) confirmed by review of medical records and screening assessment.
• Best Corrected Visual Acuity (BCVA) obtained during the screening period is in the range of 20/40+ to 20/400- (ETDRS letter score in the range of 18 to 73, inclusive).
• Duration of vision loss from CRVO \>= 6 months to \<=42 months.
• Previous eye treatment with intravitreal or periocular steroids, laser or intraocular surgery within 6 months prior to enrollment (i.e., date ICF signed) or treatment expected to be given during the study period.
• For eyes requiring treatment to prevent recurrent macular edema, on-going intravitreal anti-VEGF treatment is expected to be given at an interval \< every 8 weeks during the study period or anti-VEGF therapy was started less than 24 weeks prior to informed consent.
• History of concurrent ocular herpes infection.
• Active non-herpetic eye infection diagnosed within 8 weeks from enrollment (i.e., date Informed Consent Form (ICF) signed).
• Glaucoma requiring treatment with more than 2 medications, laser or intraocular surgery.
• Active uveitis or history of recurrent uveitis or uveitis involving the posterior segment.
• Presence of cataract that is impairing vision.
• Presence of lens or lens implant subluxation.
• History of ocular trauma that is currently impairing vision.
• Any concurrent optic nerve or retinal disease that is visually significant or likely to progress to visual significance during the 1-year study follow-up. The excluded eyes include eyes with AREDS category 2 to 3 age-related macular degeneration (AMD) with foveal involvement of drusen or RPE changes, and any AREDS category 4 AMD eyes. For eyes with ERM, the excluded eyes include eyes with OCT evidence of foveal deformation. For optic nerve disease, eyes with any associated visual field deficit or history of associated CNVM are excluded. For glaucoma eyes, eyes requiring glaucoma laser trabeculectomy or glaucoma surgery to maintain IOP are excluded.
• Active retinal or iris neovascularization.
• Macular edema requiring on-going therapy or where treatment is expected during the study period, with the exception of anti-VEGF treatment given at an interval of 8 weeks or greater.

Sponsors & Collaborators

• The Emmes Company, LLC: lead
• National Eye Institute (NEI): collaborator
• University of California, Davis: collaborator

Study Sites (1)

Department of Ophthalmology & Vision Science, University of California Davis Eye Center

Sacramento, California, 95817, United States

Location

Related Publications (3)

• Park SS, Bauer G, Abedi M, Pontow S, Panorgias A, Jonnal R, Zawadzki RJ, Werner JS, Nolta J. Intravitreal autologous bone marrow CD34+ cell therapy for ischemic and degenerative retinal disorders: preliminary phase 1 clinical trial findings. Invest Ophthalmol Vis Sci. 2014 Dec 9;56(1):81-9. doi: 10.1167/iovs.14-15415.

  PMID: 25491299 BACKGROUND

• Park SS, Bauer G, Fury B, Abedi M, Perotti N, Colead-Bergum D, Nolta JA. Phase I Study of Intravitreal Injection of Autologous CD34+ Stem Cells from Bone Marrow in Eyes with Vision Loss from Retinitis Pigmentosa. Ophthalmol Sci. 2024 Jul 31;5(1):100589. doi: 10.1016/j.xops.2024.100589. eCollection 2025 Jan-Feb.

  PMID: 39328826 BACKGROUND

• Romano F, Lamanna F, Gabrielle PH, Teo KYC, Battaglia Parodi M, Iacono P, Fraser-Bell S, Cornish EE, Nassisi M, Viola F, Agarwal A, Samanta A, Chhablani J, Staurenghi G, Invernizzi A. Update on Retinal Vein Occlusion. Asia Pac J Ophthalmol (Phila). 2023 Mar-Apr 01;12(2):196-210. doi: 10.1097/APO.0000000000000598. Epub 2023 Feb 14.

  PMID: 36912792 DERIVED

MeSH Terms

Conditions

Retinal Vein Occlusion; Retinal Diseases; Eye Diseases

Condition Hierarchy (Ancestors)

Venous Thrombosis; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Principal Investigator of the TRUST Data Coordinating Center
• Organization: The Emmes Company, LLC

trust@emmes.com

301-251-1161

Study Officials

• Susanna S Park, MD, PhD

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The participant, examining ophthalmologist, visual acuity examiner, photographers and OCT, perimetry, and ERG technicians will remain masked to study treatment assignment for study duration.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2019
• First Posted: June 11, 2019
• Study Start: October 22, 2019
• Primary Completion: November 7, 2023
• Study Completion: November 9, 2023
• Last Updated: December 2, 2024
• Results First Posted: December 2, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Time Frame will be determined.
• Access Criteria: Confidentiality agreements will be required before anonymized data will be shared.

Locations

US (1)