Stem Cell Gene Therapy for Cystinosis
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|ClinicalTrials.gov Identifier: NCT03897361|
Recruitment Status : Recruiting
First Posted : April 1, 2019
Last Update Posted : May 28, 2021
|Condition or disease||Intervention/treatment||Phase|
|Lysosomal Storage Diseases Cystinosis||Genetic: CTNS-RD-04||Phase 1 Phase 2|
Cystinosis is a rare inherited recessive disease belonging to the family of Lysosomal Storage Disorders and is characterized by lysosomal accumulation of cystine in all the cells of the body leading to multi-organ failure. Cystinosis has a devastating impact on the affected individuals, primarily children, and young adults, even with cysteamine treatment. The prevalence of cystinosis is 1 in 100,000 to 1 in 200,000. The gene involved in cystinosis is the gene CTNS that encodes for the transmembrane lysosomal cystine transporter - cystinosin. The current standard of care does not prevent the progression of the disease and significantly impacts the quality of life of patients with cystinosis.
For this study, up to 6 subjects meeting eligibility criteria will be transplanted following a 3-cohort staggered treatment design with 2 subjects per cohort. The first 2 cohorts will consist of 4 adults (18 years or older), potentially followed by a cohort consisting of 2 adolescents or adults (> 14 years old). Following the informed consent process, enrolled subjects will be screened to confirm full eligibility for participation. Eligible subjects will undergo hematopoietic stem cell (HSC) mobilization and collection (leukapheresis). A portion of cells will be kept as "back-up" for rescue purpose if necessary, and a portion will be ex vivo gene-modified with a lentiviral vector, pCCL-CTNS, to express CTNS gene (product name: CTNS-RD-04). The subjects will receive marrow cytoreduction with busulfan prior to infusion of CTNS-RD-04. Subjects will discontinue cysteamine treatment during the assessment period. The assessment follow-up period will include an initial 2 years of active end-point evaluations, where the subjects will be evaluated at 3-, 6-, 9-, 12-, 18- and 24-months post-transplantation. A Long-Term Follow-Up study (LTFU) for a total 15-year follow-up period will be offered to all subjects.
The objectives of this Phase 1/2 clinical study are to assess the safety/tolerability of CTNS-RD-04, and its efficacy through a number of clinical, molecular and biochemical assessments.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||6 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||This study will include up to 6 subjects and follows a 3-cohort staggered treatment design with 2 subjects per cohort. The first 2 cohorts will consist of 4 adults (18 years or older), potentially followed by a cohort consisting of 2 adolescents or adults (>14 years old).|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1/2 Study to Determine Safety and Efficacy of Transplantation With Autologous Human CD34+ Hematopoietic Stem Cells (HSC) From Mobilized Peripheral Blood Stem Cells (PBSC) of Patients With Cystinosis Modified by Ex Vivo Transduction Using pCCL-CTNS or pCDY.EFS.CTNS.T260I Lentiviral Vector|
|Actual Study Start Date :||July 8, 2019|
|Estimated Primary Completion Date :||August 2023|
|Estimated Study Completion Date :||March 2024|
Experimental: CTNS-RD-04 Gene Therapy
This is a single arm study without randomization. Eligible subjects will receive the final product: CTNS-RD-04.
Peripheral blood autologous CD34+ enriched cell fraction transduced with lentiviral vector, pCCL-CTNS, that contains the human CTNS complementary deoxyribonucleic acid (cDNA) sequence.
- Evaluation of safety - Absence of Severe Adverse Events (SAEs) due to the investigational product [ Time Frame: Up to 24 months post transplant. ]Safety and tolerability will be assessed in terms of incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
- Evaluation of safety - Absence of Replication-Competent Lentivirus (RCL) [ Time Frame: Up to 24 months post transplant. ]Safety and tolerability will be measured by number of subjects with Replication Competent Lentivirus (RCL)
- Evaluation of safety - Absence of genotoxicity [ Time Frame: Up to 24 months post transplant. ]Safety and tolerability will be measured by absence of insertional mutagenesis, monoclonal expansion.
- Evaluation of safety - Event-free survival [ Time Frame: Up to 24 months post transplant. ]Safety and tolerability will be measured by Event-free survival over the 24 months after stem cell transplantation
- Evaluation of efficacy - Change in cystine levels [ Time Frame: Up to 24 months post transplant. ]Efficacy will be measured by evaluating the impact of treatment with CTNS-RD-04 on cystine levels in the blood, and cystine crystal counts in the intestinal mucosa and skin, and eye with the help of Mass Spectrometry and Confocal Microscopy.
- Evaluation of efficacy - To evaluate the effect of treatment with CTNS-RD-04 on clinical disease outcomes [ Time Frame: Up to 24 months post transplant. ]
Among other evaluations, clinical efficacy will be measured by evaluating the effect on clinical disease outcomes including:
- Kidney Function (test: measure Serum Cystatin C levels, unit: score from 1 to 5 based on the stage of dialysis); (test: measure serum and urine phosphate levels, unit: mg/dL);
- Vision (test: Pachymetry, unit: millimeter); (test: Anterior Segment - Optical Coherence Tomography, unit: millimeter or millimeter square);
- Muscle strength (test: grip strength, unit: scale between 0/5 and 5/5);
- Pulmonary function (test: Spirometry, unit: percentage);
- Neurological and Psychometric function (test: Beery Test of Visual Motor Integration, neurological examination to evaluate motor coordination, tone, strength, and reflexes, unit: numerical score).
- Evaluation of efficacy - Change in Quality of Life [ Time Frame: Up to 24 months post transplant. ]Efficacy will be measured by evaluating changes in quality of life with the help of Health-Related Quality of Life (HRQoL) which will assess the impact of treatment with CTNS-RD-04 on quality of life.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03897361
|Contact: Patient Care Manager||1-844-317-7836 (STEM)||email@example.com|
|United States, California|
|University of California San Diego||Recruiting|
|La Jolla, California, United States, 92093|
|Contact: Patient Care Manager 844-317-7836 firstname.lastname@example.org|
|Principal Investigator: Stephanie Cherqui, Ph.D.|
|Principal Investigator: Bruce Barshop, M.D., Ph.D.|
|Principal Investigator: Edward D. Ball, M.D.|
|Sub-Investigator: Ranjan Dohil, M.D.|
|Sub-Investigator: Nadine Benador, M.D.|
|Sub-Investigator: Robert Mak, M.D., Ph.D.|
|Sub-Investigator: Magdalene Dohil, M.D.|
|Sub-Investigator: Eric Nudleman, M.D., Ph.D.|
|Sub-Investigator: Susan Phillips, M.D.|
|Sub-Investigator: Doris Tauner, M.D.|
|Sub-Investigator: Kathleen Rickert, M.D.|
|Sub-Investigator: Jack Bui, M.D.|
|Sub-Investigator: Natalie Afshari, M.D.|
|Principal Investigator:||Stephanie Cherqui, Ph.D.||University of California, San Diego (UCSD)|