What side effects are associated with this type of intervention?

Gene-corrected hematopoietic stem cell treatments for cystinosis, such as CTNS-RD-04 or CTNS-RD-04-LB, can have side effects related to the transplantation process, including infections, graft-versus-host disease (GVHD), and organ toxicity. The conditioning regimen used prior to stem cell infusion may also cause nausea, fatigue, and increased susceptibility to infections.

What prior FDA approvals exist?

Cystinosis is primarily treated with cysteamine, which helps to reduce cystine accumulation in cells. The FDA has approved cysteamine bitartrate (Cystagon) and delayed-release cysteamine bitartrate (Procysbi) for this purpose. While these treatments manage the symptoms, they do not correct the underlying genetic defect. The investigational product CTNS-RD-04 or CTNS-RD-04-LB involves gene-corrected hematopoietic stem cells to address the root cause of cystinosis by correcting the defective gene. This approach is still under clinical investigation and represents a novel therapeutic strategy compared to existing treatments.

What other types of research exist?

Promising novel alternatives for cystinosis treatment in 2024 may include advancements in CRISPR-Cas9 gene editing technology, which allows precise correction of genetic mutations, and other gene therapy approaches such as lentiviral vector-based therapies. Additionally, developments in induced pluripotent stem cells (iPSCs) for generating patient-specific stem cells and organoid models for personalized medicine could offer new treatment avenues.

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Gene Therapy

Stem Cell Gene Therapy for Cystinosis

Q: What is the mechanism of action of this treatment?

The most common treatment for cystinosis being studied involves the use of gene-corrected hematopoietic stem cells, such as CTNS-RD-04 or CTNS-RD-04-LB. This approach aims to correct the defective CTNS gene responsible for cystinosis by introducing functional copies of the gene into the patient's stem cells. These corrected stem cells can then produce healthy cells that express the functional cystinosin protein, which helps to reduce the accumulation of cystine in cells. This treatment is significant for cystinosis patients as it addresses the root cause of the disease, potentially offering a long-term solution and reducing the need for lifelong cystine-depleting medications.

Phase 1 & 2

Waitlist Available

Led By Stephanie Cherqui, Ph.D.

Research Sponsored by University of California, San Diego

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Subject has an adequate hepatic function: Bilirubin ≤ 2.0 mg/ dL, ALT ≤ 3 x institution's upper limit of normal (ULN) U/L

Subject has adequate thyroid function (with or without thyroid replacement therapy): TSH 0.27-4.2 mIU/mL, Total T4 ≤ 2 x ULN mcg/dL

Must not have

Subject is receiving cytotoxic or immunosuppressive agents, other than for kidney transplant, within 60 days prior to screening or requires treatment with such agents prior to treatment with ex vivo gene therapy

Subject has impaired cardiac function within 90 days prior to screening including any of the following: Myocardial infarction, Clinically significant abnormal electrocardiogram (ECG), Ejection fraction of < 40%, Uncontrolled arrhythmia, Other clinically significant heart disease (e.g., congestive heart failure, uncontrolled hypertension, history of labile hypertension)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 24 months post transplant.

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new treatment for cystinosis using patients' own cells that are improved in a lab and then returned to them to help prevent harmful cystine buildup. The study aims to see if this approach is safe and effective.

Who is the study for?

This trial is for individuals with cystinosis, a specific lysosomal storage disease. Eligible participants must be at least 14 years old, have adequate organ function, and agree to use contraception or remain abstinent for two years post-treatment. They should not have had major surgery recently, previous gene therapy or stem cell transplants, certain allergies or infections, substance addiction issues, severe medical disorders, or be on immunosuppressive drugs.

What is being tested?

The study tests the safety and effectiveness of CTNS-RD-04 and CTNS-RD-04-LB (LentiBOOST), which are gene-corrected hematopoietic stem cells from patients with cystinosis. It's a Phase 1/2 trial where these enriched cells are reintroduced into the patient to see if they can correct the genetic defect causing their condition.

What are the potential side effects?

Potential side effects aren't specified but may include reactions related to stem cell transplantation such as immune responses against the new cells (graft-versus-host disease), infection risks due to weakened immunity during conditioning treatment before transplanting the corrected cells, infusion-related reactions and bone marrow suppression.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My liver is functioning well, with normal bilirubin and ALT levels.

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My thyroid function is within the normal range, with or without medication.

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I agree to use effective birth control or remain abstinent for two years after my transplant.

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I have been diagnosed with cystinosis, showing early signs and have high cystine in my cells or crystals in my eyes.

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I agree to use effective birth control or remain abstinent for two years after my transplant.

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My kidney function is normal, with creatinine levels less than twice the upper limit.

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I can care for myself but may not be able to do active work.

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My blood counts are within the required range for treatment.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I haven't taken any strong immune or cancer drugs in the last 60 days, except for a kidney transplant.

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I have had heart problems or an abnormal heart test in the last 3 months.

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My lung function is significantly reduced.

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I have tested positive for a virus like HIV, Hepatitis B/C, or West Nile.

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I have received gene therapy before.

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I am a woman who could become pregnant, am pregnant, or am nursing.

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I have had a bleeding disorder or needed blood-thinning medicine in the last 3 months.

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I do not have an active infection.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 24 months post transplant.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 24 months post transplant.

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 24 months post transplant. for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Evaluation of safety - Absence of Replication-Competent Lentivirus (RCL)

Evaluation of safety - Absence of Severe Adverse Events (SAEs) due to the investigational product

Evaluation of safety - Absence of genotoxicity

+1 more

Secondary study objectives

Evaluation of efficacy - Change in Quality of Life

Evaluation of efficacy - Change in cystine levels

Therapeutic procedure

+1 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Gene Therapy with CTNS-RD-04 or CTNS-RD-04-LB (where the suffix "-LB" stands for LentiBOOST)Experimental Treatment1 Intervention

This is a single arm study without randomization. Eligible subjects will receive the final product: CTNS-RD-04 or CTNS-RD-04-LB (where the suffix "-LB" stands for LentiBOOST).

0 / 16Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatment for cystinosis being studied involves the use of gene-corrected hematopoietic stem cells, such as CTNS-RD-04 or CTNS-RD-04-LB. This approach aims to correct the defective CTNS gene responsible for cystinosis by introducing functional copies of the gene into the patient's stem cells. These corrected stem cells can then produce healthy cells that express the functional cystinosin protein, which helps to reduce the accumulation of cystine in cells. This treatment is significant for cystinosis patients as it addresses the root cause of the disease, potentially offering a long-term solution and reducing the need for lifelong cystine-depleting medications.

Tetrahydrobiopterin deficiency in the pathogenesis of Fabry disease.Treatment of Creatine Transporter (SLC6A8) Deficiency With Oral S-Adenosyl Methionine as Adjunct to L-arginine, Glycine, and Creatine Supplements.