Current Clinical Trials
Community Update: Novartis CYStem Phase I/II Clinical Trial in Cystinosis Posted on ClinicalTrials.gov
Dear Cystinosis Community,
We are pleased to share details about the CYStem clinical trial, which was recently published on ClinicalTrials.gov. Details can be found here: Study Details | DFT383 in Pediatric Participants With Nephropathic Cystinosis | ClinicalTrials.gov
What is CYStem?
CYStem is an open-label, multi-center, Phase I/II study to assess safety, tolerability and efficacy of DFT383 in pediatric participants with nephropathic cystinosis. Novartis has partnered with cystinosis patients, their caregivers and patient organizations to guide the design of this trial and have included their feedback wherever possible. How will the trial work? The purpose of the study is to investigate if DFT383 is safe and effective in children aged 2-5 years who have nephropathic cystinosis. DFT383 is a cellular gene therapy. A standard of care (SoC) group will also be enrolled, in which children will not receive study treatment, and will continue treatment with standard of care (i.e. cysteamine). The information from this SoC group will be used to better understand the disease and the results observed in the children receiving DFT383. The two groups will be run at the same time. Investigational sites may participate in one or both groups.
Who can participate?
- The trial aims to include approximately 30 participants.
- Approximately 15 participants will receive treatment with DFT383 in 3 groups (1A, 1B and 1C) dosed in a staggered approach. The total study duration for a participant in Group 1 will be up to 32 months for the primary study period.
- Approximately 15 participants meeting similar inclusion/exclusion criteria and receiving SoC will be enrolled.
The Schedule of Activities will be reduced for this Group 0. Group 0 is not a direct control but will provide essential context for interpreting the results observed in the participants receiving DFT383.The total duration for a participant in Group 0 will be up to 24 months. - Recruitment will start in the second quarter of 2025.
- There will be various trial locations which continue to be added over the next several months.
What are the key criteria for participation?
- Key Inclusion Criteria:
- Informed consent in writing from parent(s) or legal guardian(s) must be provided
- 2 to 5 years of age (including 5 years and 364 days old) at Screening
- Weight-for-stature is ≥ the third percentile and is ≥ 10 kg
- Oral cysteamine therapy for at least 6 months
- Clinical diagnosis of nephropathic cystinosis
- Laboratory evidence of renal Fanconi syndrome (RFS)
- Preserved kidney function (eGFR ≥ 90mL/min/1.73m2)
- Received all age-appropriate vaccinations
- Key exclusion Criteria for Group 1 and 0:
- A history of kidney transplantation
- A prior or planned bone marrow or stem cell transplantation or prior treatment with gene therapy
- History of malignancy
- A severe or uncontrolled medical disorder
- Major surgery within 90 days
- The following exclusion criteria only apply to Group 1 only as they are important for procedures related to DFT383 treatment:
- Indomethacin within 2 weeks prior to Screening
What are some of the key things the study is looking to assess?
- Key criteria for both Group 0 and Group 1:
- Adverse events and serious adverse events
- Physical exam, blood and urine test, electrocardiogram, vital signs
- Caregiver interview
- Cystine levels in white blood cells and in the cornea
- Oral and ophthalmic cysteamine use
- Key criteria for Group 1 only as they are related to DFT383 treatment:
- Blood cell count normalization
- Lentivirus in blood
- Malignancies
- Reversal of Renal Fanconi Syndrome
Patients and caregivers interested in enrolling in the study should reach out to their primary physician. In the meantime, we look forward to a successful start to this important trial and will be in touch with any further relevant updates.
Kind regards,
The Novartis CYStem Cystinosis Study Team
Novartis Pharmaceuticals
1-888-NOW-NOVA (1-888-669-6682)
novartis.email@novartis.com
This statement is not intended to establish any legally enforceable rights, obligations, or commitments on Novartis.
Stem Cell Therapy for Cystinosis - UC San Diego
The Food and Drug Administration approved the first stem cell and gene therapy clinical trial for six adult patients with cystinosis in November 2018.
Volunteers – Note: Phase I/II of the clinical trial recruited all six volunteers who are doing well. The next phase of the trial will be conducted by Novartis, click the link for the Cystinosis Community Statement from Novartis.
The Phase I / II human clinical trials were held at UC San Diego Health in San Diego, CA. The recruitment period for this phase has been completed. Individuals were 18 years or older with specific eligibility requirements to participate, listed below. The subsequent phases of the clinical trials may include children, however, timing, and approvals have yet to be determined. The trials were available to individuals worldwide, though priority was given to U.S. patients.
- Male or female who are 18 years and older of age.
- Diagnosed with cystinosis, i.e., early onset of Fanconi syndrome, and history of elevated white blood cell cystine level and/or history of or presence of cystine crystals in the eye.
- Must be at least one year post kidney transplant status.
- Must have adequate blood, thyroid, kidney and liver functions.
- Must be willing to use highly effective contraception whether male or female.
- Must be willing to comply with the study restrictions and requirements.
- Must be willing to discontinue cysteamine therapy (oral and/or eye drop) for various periods of time while in this study.
- Must have a family or friend caretaker available at all times during the study.
Does Cystinosis Affect Brain Function? New Study Seeks to Provide Answers
This CRF-funded study is now recruiting patient volunteers. Dr. Sophie Molholm’s project aims to gain a better understanding of how brain function is affected by cystinosis, focusing on auditory and visual processing and memory. Contact Ana Francisco at ana.alvesfrancisco@einsteinmed.org or call (718) 862-1824 for more information. Download PDF of Brain Study Flyer.
Characterization of Distal Myopathy and Dysphagia in Nephropathic Cystinosis and Evaluation for Muscle Regenerative Capacity
Research Study
NOW OPEN TO ADULTS 18+ YEARS
Dr. Reza Seyedsadjadi and Dr. Florian Eichler of the Massachusetts General Hospital (MGH) Center for Rare Neurological Diseases are conducting a study to learn more about muscle weakness and swallowing difficulties in Nephropathic Cystinosis and the ability of these muscles to regenerate (rebuild themselves). This study is currently funded by the Cystinosis Research Foundation (CRF).
For more information about the study click here.
Therapeutic Strategy for Cystinotic Nephropathy with iPS Cells, Dr. Benjamin “Beno” Freedman, PhD, University of Washington, Seattle, Washington
The goal of our CRF project is to use human mini-kidneys as surrogates for patients, to explore the potential of kidney regeneration, gene therapy, and drug discovery for cystinosis. We are seeking to recruit patients with cystinosis, and turn their urine into stem cells and kidney grafts, which we will test for transplantability. There is no obligation. Study participation is on a purely volunteer basis and is free of charge without compensation. If you are interested in joining the study or have questions about it, please contact Dr. Freedman for more information at benof@uw.edu.
The Effect of Resistance Exercise on Muscle Dysfunction in Cystinosis
A CRF research study being conducted by Richard Reimer, MD, Associate Professor of Neurology, Stanford University School of Medicine, Palo Alto, California. If you are interested in participating in the study please contact Dr. Reimer at rjreimer@stanford.edu for more details.
Phase 2 Study ELX- 02 in Patients with Nephropathic Cystinosis Montreal, Canada – POSTPONED
As many of you know, we launched the trial last fall and recruited the first small cohort to test a range of doses for effect on WBC cystine and safety. This first round identified the dosing threshold at which ELX-02 begins to reverse cystine accumulation and showed no auditory or renal side effects. The preliminary results from this study have shown clear biologic activity and are very exciting. However, due to study design limitations, this study has been stopped and a new design is being considered. Also, with the unexpected arrival of the COVID19 epidemic, most such clinical trials are suspended in North America.
In the interim, we will use the time to study our new CtnsW138X mouse model to ascertain whether early ELX-02 treatment can prevent Fanconi syndrome. I will keep the community updated from time to time on the CRF registry website.
For further information, please contact Dr. Paul Goodyer of McGill University Health Center in Montreal, Canada or call for more information at (514) 412-4400 ext. 22953 or email Murielle M. Akpa, PhD, murielle.akpa@muhc.mcgill.ca.
