Treatment of Central Retinal Vein Occlusion Using Stem Cells Study
NCT ID: NCT03981549
Last Updated: 2024-12-02
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE1/PHASE2
16 participants
INTERVENTIONAL
2019-10-22
2023-11-09
Brief Summary
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Detailed Description
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Participants will be randomized 1:1 to immediate cell therapy/deferred sham therapy or immediate sham therapy/deferred cell therapy. At month 6, the cell treated eye will receive sham treatment and the sham treated eye will get cell therapy. The cellular therapy involves bone marrow aspiration, isolation of CD34+ cells from the aspirate under Good Manufacturing Practice (GMP) conditions, and intravitreal injection of isolated CD34+ cells. The sham therapy involves a sham bone marrow aspiration with penetration of the skin but no penetration of the bone and a sham intravitreal injection without penetrating the eye. The participant, examining ophthalmologist, visual acuity examiner, photographers and OCT, perimetry, and electroretinography (ERG) technicians will remain masked to study treatment assignment for study duration. A comprehensive eye examination with ETDRS best-corrected visual acuity, optical coherence tomography (OCT) and OCT angiography (OCTA), autofluorescence, fundus photography, fluorescein angiography, microperimetry, and electroretinography will be performed at baseline and serially. A subset of participants with good fixation on microperimetry and clear media on exam and commercial-grade OCTA and who give consent will have ultra-high resolution cellular retinal imaging using research-grade OCT and OCTA and adaptive optics-OCT at baseline. Participants with high quality images will have repeat imaging at 1 month after stem cell treatment, with at least 2 of the participants randomized to the deferred cellular therapy arm also having imaging 1 month after sham therapy. Post-release flow cytometry characterization will be performed to determine the composition of the CD34+ enriched final product in terms of hematopoietic versus angiogenic stem cells based on cell surface markers (i.e., CD133(+)/CD45(+)/CD34(+) vs CD31(+)/VEGFR-2(+)/CD45(-)/CD34(+)). The long-term objective is to determine whether intravitreal autologous CD34+ cell therapy can minimize, or reverse vision loss associated with retinal ischemia without compromising safety.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
TRIPLE
Study Groups
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Immediate Cellular Therapy / Deferred Sham Therapy
At baseline: Bone marrow aspiration followed by intravitreal injection of CD34+ cells.
At 6 months: Sham bone marrow aspiration and sham intravitreal injection.
Autologous Bone Marrow CD34+ Stem Cells
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.
Sham Therapy
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 Sham Therapy / Deferred Cellular Therapy
At baseline: Sham bone marrow aspiration followed by sham intravitreal injection.
At 6 months: Bone marrow aspiration followed by intravitreal injection of CD34+ cells.
Autologous Bone Marrow CD34+ Stem Cells
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.
Sham Therapy
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
Interventions
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Autologous Bone Marrow CD34+ Stem Cells
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.
Sham Therapy
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
Eligibility Criteria
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Inclusion Criteria
* 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.
* Age \>=18 years
* Female participants of child-bearing potential must not be pregnant or breastfeeding and have a negative urine pregnancy test within 14 days prior to sham injection and/or CD34+ cell injection.
* Females of childbearing potential must have had a hysterectomy, be completely abstinent from intercourse or must agree to practice effective contraception for the duration of the study. Acceptable methods of contraception include hormonal contraception, intrauterine device, barrier methods (diaphragm, condom) with spermicide, or surgical sterilization (tubal ligation).
* Able and willing to sign informed consent.
* Able to keep follow-up appointments for at least 12 months as determined by the investigator.
Exclusion Criteria
* 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.
* Significant media opacity precluding view of the fundus for examination, photography or optical coherence tomography (OCT) including cataract and vitreous haze.
* High myopia (\>= 9 diopters)
* Amblyopia
* Other cause contributing to vision loss at screening.
* History of any of the following procedures: corneal transplant, glaucoma surgery, or intraocular silicone oil.
* Concurrent treatment with an investigational drug or device.
* Concurrent use of systemic immunosuppressive therapy or history of use within 3 months prior to enrollment (i.e., date ICF signed).
* Concurrent use of anticoagulation therapy except for aspirin without an acceptable safe stopping plan for study treatments.
* Known history of coagulopathy or other hematologic abnormality that may put participant at risk for bleeding or infection or raise concerns about quality or quantity of CD34+ cells isolated.
* History of allergy to fluorescein dye.
* Participant who has had a prior or concomitant malignancy with the exception of the following: 1) adequately treated basal or squamous cell carcinoma of the skin, or 2) any other malignancy from which the patient has remained disease free for more than five years.
* Current active systemic infection as evidenced by fever greater than 100.4 or any evidence of systemic infection as determined by the study physician.
* Any diagnosis of active infection or vaccination within 8 weeks of study treatment.
* Diabetes mellitus with known systemic complications by self-report or physician-determined by medical history or examination.
* History of prior radiotherapy to head/neck area.
* Poorly controlled hypertension with systolic \> 180 or diastolic \> 95.
* Serious medical or psychiatric condition that, in the opinion of the Investigator, would make study participation hazardous to the participant or compromise study findings or would prevent the participant from completing the study.
* Any physical characteristic that precludes ability to perform study diagnostic testing.
18 Years
ALL
No
Sponsors
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National Eye Institute (NEI)
NIH
University of California, Davis
OTHER
The Emmes Company, LLC
INDUSTRY
Responsible Party
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Principal Investigators
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Susanna S Park, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
University of California, Davis
Locations
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Department of Ophthalmology & Vision Science, University of California Davis Eye Center
Sacramento, California, United States
Countries
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References
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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.
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.
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.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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