CSB-001 Ophthalmic Solution for Limbal Stem Cell Deficiency
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Claris Biotherapeutics, Inc.
No Placebo Group
Trial Summary
What is the purpose of this trial?This study will enroll subjects with qualifying limbal stem cell deficiency (LSCD). All subjects will receive CSB-001 investigational drug in either one or both study eyes. The study is comprised of two identical phases (Dosing Phase I and II) of test article dosing separated by a 31- to 40-day period, the Dosing Holiday, where no test article is administered. Dosing Phase II is followed by an observational, noninterventional phase (Observation Phase).
Is the drug CSB-001 Ophthalmic Solution 0.1% a promising treatment for limbal stem cell deficiency?Yes, CSB-001 Ophthalmic Solution 0.1% is a promising treatment for limbal stem cell deficiency because it uses a special protein to help repair and regenerate the eye's surface, which can improve vision and eye health.710111213
What safety data exists for CSB-001 Ophthalmic Solution?The provided research does not directly address the safety data for CSB-001 Ophthalmic Solution or its related formulations. The studies focus on the effects of hepatocyte growth factor (HGF) in various contexts, such as its neuroprotective effects in retinal injuries and its presence in retinal disorders. However, they do not provide specific safety data for the ophthalmic solution in question.12459
Do I have to stop taking my current medications for the trial?The trial protocol does not specify if you need to stop taking your current medications. However, if you are taking Acthar, you must have a stable dose for about 8 weeks and plan to continue the same dose during the trial.
What data supports the idea that CSB-001 Ophthalmic Solution for Limbal Stem Cell Deficiency is an effective treatment?The available research shows that hepatocyte growth factor (HGF), which is a key component of CSB-001 Ophthalmic Solution, promotes the growth of certain eye cells. Specifically, it helps human embryonic stem cell-derived retinal pigment epithelial cells to grow, which suggests it could be beneficial in treatments involving eye cell regeneration. However, the research does not directly address its effectiveness for Limbal Stem Cell Deficiency, so more specific studies would be needed to confirm its benefits for this condition.13468
Eligibility Criteria
This trial is for individuals with limbal stem cell deficiency (LSCD), a condition affecting the eyes. Participants will receive CSB-001 Ophthalmic Solution in one or both eyes if they qualify. Specific eligibility criteria are not provided, but typically include having LSCD without other major eye diseases and being able to follow the study protocol.Inclusion Criteria
I've been on a stable Acthar dose for 8 weeks with little improvement in my condition.
I have a diagnosed eye condition affecting the central part of my cornea.
Exclusion Criteria
I do not have any active eye infections.
I am scheduled for eye surgery before or by my Week 20 visit.
I had eye surgery less than 30 days ago and my healing is not complete.
Treatment Details
The safety and effectiveness of CSB-001 Ophthalmic Solution at 0.1% concentration are being tested on people with LSCD. The study has two main dosing phases separated by a break, followed by an observation phase to monitor long-term effects.
2Treatment groups
Experimental Treatment
Group I: CSB-001 QIDExperimental Treatment1 Intervention
One drop CSB-001 four times daily for two 8-week dosing periods in the study eye(s)
Group II: CSB-001 BIDExperimental Treatment1 Intervention
One drop CSB-001 twice daily for two 8-week dosing periods in the study eye(s)
Find a clinic near you
Research locations nearbySelect from list below to view details:
Legacy Devers Eye InstitutePortland, OR
Stuart A. Terry, MD PASan Antonio, TX
Midwest Cornea Associates, LLCCarmel, IN
Loma Linda University Eye InstituteLoma Linda, CA
More Trial Locations
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Who is running the clinical trial?
Claris Biotherapeutics, Inc.Lead Sponsor
References
Hepatocyte growth factor in vitreous fluid of patients with proliferative diabetic retinopathy and other retinal disorders. [2019]To determine whether hepatocyte growth factor (HGF) is elevated in the vitreous fluid of patients with proliferative diabetic retinopathy (PDR).
Expression and neuroprotective effect of hepatocyte growth factor in retinal ischemia-reperfusion injury. [2009]To investigate the expression and possible neuroprotective effects of hepatocyte growth factor (HGF) in a rat model of retinal ischemia-reperfusion injury.
[The effect of freezing and low molecular weight heparin treatment on the production of hepatocyte growth factor of human RPE cells]. [2018]This study is to investigate the human hepatocyte growth factor (HGF) level and proliferation of cultured human retinal pigment epithelial cells (RPE), treated with freezing, or Tedelparin (low molecular weight heparin), or both.
Hepatocyte growth factor protects RPE cells from apoptosis induced by glutathione depletion. [2013]To study the mechanism of the protective effect of hepatocyte growth factor (HGF) in oxidative injury to RPE cells induced by glutathione (GSH) depletion.
Protective effect of hepatocyte growth factor against degeneration of the retinal pigment epithelium and photoreceptor in sodium iodate-injected rats. [2013]To investigate the possible protective effect of hepatocyte growth factor (HGF) against degeneration of photoreceptors and retinal pigment epithelium (RPE) in vivo.
Aqueous humor levels of hepatocyte growth factor in retinitis pigmentosa. [2010]To determine the level of hepatocyte growth factor (HGF) in the aqueous humor of patients with retinitis pigmentosa (RP).
ABCB5 is a limbal stem cell gene required for corneal development and repair. [2022]Corneal epithelial homeostasis and regeneration are sustained by limbal stem cells (LSCs), and LSC deficiency is a major cause of blindness worldwide. Transplantation is often the only therapeutic option available to patients with LSC deficiency. However, while transplant success depends foremost on LSC frequency within grafts, a gene allowing for prospective LSC enrichment has not been identified so far. Here we show that ATP-binding cassette, sub-family B, member 5 (ABCB5) marks LSCs and is required for LSC maintenance, corneal development and repair. Furthermore, we demonstrate that prospectively isolated human or murine ABCB5-positive LSCs possess the exclusive capacity to fully restore the cornea upon grafting to LSC-deficient mice in xenogeneic or syngeneic transplantation models. ABCB5 is preferentially expressed on label-retaining LSCs in mice and p63α-positive LSCs in humans. Consistent with these findings, ABCB5-positive LSC frequency is reduced in LSC-deficient patients. Abcb5 loss of function in Abcb5 knockout mice causes depletion of quiescent LSCs due to enhanced proliferation and apoptosis, and results in defective corneal differentiation and wound healing. Our results from gene knockout studies, LSC tracing and transplantation models, as well as phenotypic and functional analyses of human biopsy specimens, provide converging lines of evidence that ABCB5 identifies mammalian LSCs. Identification and prospective isolation of molecularly defined LSCs with essential functions in corneal development and repair has important implications for the treatment of corneal disease, particularly corneal blindness due to LSC deficiency.
Hepatocyte growth factor promotes the proliferation of human embryonic stem cell derived retinal pigment epithelial cells. [2020]Research that pertains to the molecular mechanisms involved in retinal pigment epithelial (RPE) development can significantly contribute to cell therapy studies. The effects of periocular mesenchymal cells on the expansion of RPE cells remain elusive. We have examined the possible proliferative role of hepatocyte growth factor (HGF) as a mesenchymal cell secretory factor against human embryonic stem cell derived RPE (hESC-RPE). We found that the conditioned medium of human mesenchymal stem cells from apical papilla and/or exogenous HGF promoted proliferation of the hESC-RPE cells as single cells and cell sheets, in addition to rabbit RPE sheets in vitro. Blockage of HGF signaling by HGF receptor inhibitor, PHA-665752, inhibited proliferation of hESC-RPE cells. However, differentiation of hESCs and human-induced pluripotent stem cells to a rostral fate and eye-field specification was unaffected by HGF. Our in vivo analysis showed HGF expression in periocular mesenchymal cells after optic cup formation in chicken embryos. Administration of HGF receptor inhibitor at this developmental stage in chicken embryos led to reduced eye size and disorganization of the RPE sheet. These findings suggested that HGF administration could be beneficial for obtaining higher numbers of hESC-RPE cells in human preclinical and clinical trials.
First-in-human phase I trial of anti-hepatocyte growth factor antibody (YYB101) in refractory solid tumor patients. [2022]Label="BACKGROUND" NlmCategory="BACKGROUND">YYB101, a humanized monoclonal antibody against hepatocyte growth factor (HGF), has shown safety and efficacy in vitro and in vivo. This is a first-in-human trial of this antibody.
Isolation and enrichment of melanocytes from human corneal limbus using CD117 (c-Kit) as selection marker. [2021]Limbal melanocytes (LM) are located in the basal epithelial layer of the corneoscleral limbus and interact with adjacent limbal epithelial progenitor cells. The exploration of their biological role in the maintenance of the limbal stem cell niche has been limited by the difficulty of LM isolation and cultivation. Here, we report on a facile protocol for the efficient isolation and enrichment of pure populations of human LMs by fluorescence-activated cell sorting (FACS) using antibodies raised against the cell surface marker CD117 (c-Kit). The enriched LMs retain self-renewal capacity and sustained melanin production, and are suitable to study the potential of LMs in stem cell-based corneal tissue engineering.
Efficient Isolation and Functional Characterization of Niche Cells from Human Corneal Limbus. [2022]The fate decision of limbal epithelial progenitor cells (LEPC) at the human corneal limbus is determined by the surrounding microenvironment with limbal niche cells (LNC) as one of its essential components. Research on freshly isolated LNC which mainly include limbal mesenchymal stromal cells (LMSC) and limbal melanocytes (LM) has been hampered by a lack of efficient protocols to isolate and purify these cells. We devised a protocol for rapid retrieval of pure LMSC, LM and LEPC populations by collagenase digestion of limbal tissue and subsequent fluorescence-activated cell sorting (FACS) using antibodies against CD90 and CD117. The sorted cells were characterized by immunophenotyping and functional assays. The effects of LMSC and LM on LEPC were studied in 3D co-cultures and LEPC differentiation status was assessed by immunohistochemistry. Enzymatic digestion and flow sorting yielded pure populations of LMSC (CD117-CD90+), LM (CD117+CD90-), and LEPC (CD117-CD90-). The LMSC exhibited self-renewal capacity (55.0 ± 4.6 population doublings), expressed mesenchymal stem cell markers (CD73, CD90, CD105, and CD44), and transdifferentiated to adipocytes, osteocytes, or chondrocytes. The LM exhibited self-renewal capacity and sustained melanin production. The sorted LEPC expressed epithelial progenitor markers (CK14, CK19, and CK15) and showed a colony-forming ability. Co-cultivation of LMSC and LM with LEPC resulted in a 4-5-layered stratified epithelium and supported the preservation of a LEPC phenotype, as reflected by increased p63+ and Ki67+ cells and decreased CK12+ cells compared with LEPC monocultures. A highly efficient isolation of pure LM, LMSC, and LEPC populations from a single preparation may allow for direct transcriptomic and proteomic profiling as well as functional studies on native unpassaged LNC, which can be considered as proper equivalents of LNC in vivo. The developed biomimetic 3D co-culture method could provide an experimental model for investigating the functional role of LNC in the limbal stem cell niche.
Cotransplantation of Limbal Epithelial and Stromal Cells for Ocular Surface Reconstruction. [2022]To propose an improved stem cell-based strategy for limbal stem cell deficiency (LSCD) treatment.
Autologous Serum Eye Drops in the Management of Limbal Stem Cell Deficiency Associated With Glaucoma Surgery. [2023]To evaluate safety and efficacy of autologous serum eye drops (AS) in the treatment of limbal stem cell deficiency (LSCD) associated with glaucoma surgery.