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CompletedNCT03897361Updated Aug 6, 2026Results posted

Stem Cell Gene Therapy for Cystinosis

A Phase 1/2 interventional study of CTNS-RD-04 (including CTNS-RD-04-LB manufactured with LentiBOOST) in Lysosomal Storage Diseases and Cystinosis, sponsored by University of California, San Diego. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-06.

Sponsored by University of California, San Diego · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
7
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

This study is a Phase 1/2 clinical trial that will assess the safety and efficacy of enriched gene-corrected hematopoietic stem cells isolated from patients affected with cystinosis. (Investigational Product: CTNS-RD-04, including product manufactured with and without the transduction enhancer LentiBOOST [CTNS-RD-04-LB])

Read the detailed description

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 or pCDY.EFS.CTNS.T260I, to express CTNS gene (product name: CTNS-RD-04). Clinical manufacturing for patients in Cohort 3 will introduce a transduction enhancer LentiBOOST (product name for these patients will be CTNS-RD-04-LB, where the suffix "-LB" stands for LentiBOOST). 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.

02

Conditions studied

  • Lysosomal Storage Diseases
  • Cystinosis

Keywords

  • Cystinosis
  • Lysosomal Storage Disorders
  • LSD
03

In context

Lysosomal Storage Diseases

62 studies on the registry are indexed under Lysosomal Storage Diseases; 14 are open to participants now.

This study's enrollment of 7 is below the median of 12 across 32 interventional studies indexed under Lysosomal Storage Diseases.

Browse Lysosomal Storage Diseases studies →

Lead sponsor

University of California, San Diego is the lead sponsor of 958 studies on the registry; 191 are open to participants now.

Of its 110 completed or terminated interventional studies of FDA-regulated products, 70 (64%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

The following criteria must be met by all subjects considered for study participation.

  1. Cohorts 1 and 2: Male or female subject is ≥ 18 years of age.
  2. Cohort 3: Male or female subject is ≥ 14 years of age.
  3. Subject is 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.
  4. Subject has a Karnofsky Performance Status or age-dependent Lansky Performance of ≥ 60.
  5. If subject has had a kidney transplant, he or she must be at least one-year post kidney transplant status.

  6. Subject has adequate hematologic function:

    1. Absolute neutrophil count (ANC) ≥ 1.5 x 1000/mm\^3
    2. Platelet count ≥ 100 x 1000/mm\^3
    3. Hemoglobin ≥ 9.0 gm/dL

  7. Subject has an adequate hepatic function:

    1. Bilirubin ≤ 2.0 mg/ dL
    2. ALT ≤ 3 x institution's upper limit of normal (ULN) U/L

  8. Subject has an adequate renal function:

    a. Serum creatinine \<2x ULN mg/dL

  9. Subject has adequate coagulation:

    1. PT/aPTT ≤ 1.2 x ULN seconds
    2. INR ≤ 2

  10. Subject has adequate thyroid function (with or without thyroid replacement therapy):

    1. TSH 0.27-4.2 mIU/mL
    2. Total T4 ≤ 2 x ULN mcg/dL

  11. If female: female of childbearing potential (i.e., not surgically sterile [tubal ligation, hysterectomy, or bilateral oophorectomy] or not at least 2 years naturally postmenopausal) agrees to remain sexually abstinent or utilize the same acceptable form of highly effective contraception from screening through two years post-transplant.

    The acceptable forms of contraception for this study include hormonal contraceptives (oral, implant, transdermal patch, or injection) associated with inhibition of ovulation at a stable dose for at least 3 months prior to screening, barrier (condom with spermicide, diaphragm with spermicide), intrauterine device, or a partner who has been vasectomized for at least 6 months and has documented medical assessment of surgical success of a vasectomy.

    Note: males with cystinosis are sterile.

  12. If male: males must agree to remain sexually abstinent or utilize an acceptable form of highly effective contraception from screening through two years post-transplant.
  13. Subject is willing and able to comply with the study restrictions and requirements.
  14. Subject is willing to provide written informed consent/permission/assent prior to participation in the study.
  15. Subject must be willing to refrain from donating sperm after receiving the conditioning regimen. For subjects planning on (or for whom there is a possibility of) fathering children in the future, sperm banking prior to administration of conditioning regimen will be recommended.
  16. Subject must be willing to refrain from donating blood, organs, tissues, or cells for transplantation from 30 days prior to screening through any time after CTNS-RD-04 treatment.
  17. Subject must be willing and must be able (in the judgment of the investigator) to discontinue his or her cysteamine therapy (oral and/or eye drop).

Exclusion criteria

Exclusion Criteria:

  1. Subject has an active, uncontrolled, acute bacterial, viral, or fungal infection during screening or within 30 days prior to starting the conditioning regimen.

  2. Subject has positive serology at screening for any of the following:

    1. Human Immunodeficiency Virus (HIV) 1-2
    2. Human T-cell Lymphotropic Virus (HTLV) - I/II
    3. Hepatitis B core and Hepatitis B PCR positive
    4. Hepatitis C Virus (HCV)
    5. Rapid Plasma Reagin (RPR)
    6. Chagas' Disease (T. curzi)
    7. QuantiferonTB
    8. Nucleic Acid Test (NAT) for HIV
    9. West Nile Virus (WNV)
  3. Subject has a known clinically significant immunodeficiency disorder.
  4. Subject is a female of childbearing potential that is nursing, planning a pregnancy or has a positive serum pregnancy test.
  5. Subject has received a prior marrow or stem cell transplantation or is planning to receive one within 90 days of study initiation.
  6. Subject has had an active bleeding disorder within 90 days prior to screening OR requires anticoagulation therapy prior to treatment with ex vivo gene therapy.
  7. Subject has an active malignancy or history of malignancy including lymphoma (except primary, cutaneous basal cell or squamous cell cancer appropriately treated prior to transplantation).
  8. Subject has an end-stage renal disease (defined as GFR \<15 mL/min) and is already on a transplantation list or who may be planning to register for a kidney transplant within 90 days of study initiation.
  9. Subject has impaired pulmonary function (based on FEV1 of \<=50% of predicted or DLCO of \<=40 % of predicted and gender-specific normal threshold value).

  10. Subject has impaired cardiac function within 90 days prior to screening including any of the following:

    1. Myocardial infarction
    2. Clinically significant abnormal electrocardiogram (ECG)
    3. Ejection fraction of \< 40%
    4. Uncontrolled arrhythmia
    5. Other clinically significant heart disease (e.g., congestive heart failure, uncontrolled hypertension, history of labile hypertension).
  11. Subject has a severe or uncontrolled medical disorder (e.g., pancreatitis, severe liver disease, unstable diabetes mellitus) that would, in the investigators' opinion, impair their ability to receive study treatment and follow the study procedures.
  12. Subject has a history of allergic reactions attributed to compounds of similar chemical or biologic composition to Busulfan or allergy or contraindication to use of other agents used in the study, including iohexol, acid-citrate-dextrose Formula A (ACDA), G-CSF or plerixafor.
  13. Subject has a known history of drug or alcohol addiction.
  14. Subject has undergone major surgery within 90 days (or longer if not fully recovered) prior to screening.
  15. 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.
  16. Subject has previously received gene therapy at any time.
  17. Subject is currently receiving or anticipates receiving another investigational agent, device, or procedure from 30 days prior to screening through study completion.
  18. Subject has any condition, in the opinion of the investigator, that compromises compliance with study requirements.
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
7 participants (actual)

Study arms

  • Experimental
    Gene Therapy with CTNS-RD-04 (including product manufactured with and without LentiBOOST)

    This is a single-arm, open-label study without randomization. Eligible subjects received CTNS-RD-04, an autologous CD34+ hematopoietic stem cell product transduced ex vivo with a lentiviral vector encoding CTNS. During the study, manufacturing incorporated a transduction enhancer (LentiBOOST) in later participants.

    Genetic: CTNS-RD-04 (including CTNS-RD-04-LB manufactured with LentiBOOST)

Interventions

  • GeneticCTNS-RD-04 (including CTNS-RD-04-LB manufactured with LentiBOOST)

    Cryopreserved autologous CD34+ enriched hematopoietic stem/progenitor cells collected from mobilized peripheral blood and transduced ex vivo with a self-inactivating lentiviral vector (pCCL-CTNS or pCDY.EFS.CTNS.T260I) encoding the human CTNS complementary deoxyribonucleic acid (cDNA) sequence. In later participants, a transduction enhancer (LentiBOOST) was incorporated into the manufacturing process.

06

What researchers measure

Primary outcomes

  1. Safety and Tolerability: Total Number of Adverse Events (AEs) Per Participant (Pre- and Post-dose to End of Study)

    The total count of all adverse events (AEs) recorded for each dosed participant reported at any scheduled study visit starting with the first pre-dose safety visit (i.e., the first visit after informed consent and before the first administration of study drug) and continuing through the end of the treatment period. Events were coded using MedDRA and graded according to NCI CTCAE criteria. The outcome is the total count of AEs per participant.

    Time frame: From the first pre-dose safety visit to the end of the treatment period (e.g., 24 months post-dose) or the participant's last safety-assessment visit, whichever occurs later.

  2. Safety and Tolerability: Aggregate Number of Adverse Events (AEs) by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Severity (Pre-dose and Post-dose to End of Study)

    The total aggregate count of all graded adverse events (AEs) recorded for all dosed participants reported at any scheduled study visit starting with the first pre-dose safety visit (i.e., the first visit after informed consent and before the first administration of study drug) and continuing through the end of the treatment period. Events were coded using MedDRA v24.0 and graded according to NCI CTCAE version 4.03. The outcome is the total count of AEs per grade (Mild, Moderate, Severe, Life Threatening, Death).

    Time frame: From the first pre-dose safety visit to the end of the treatment period (e.g., 24 months post-dose) or the participant's last safety-assessment visit, whichever occurs later.

  3. Safety and Tolerability: Aggregate Number of Adverse Events (AEs) by Relationship to Study Treatment (Pre-dose and Post-dose to End of Study)

    The total aggregate count of all adverse events (AEs) categorized by relationship to the study treatment recorded for all dosed participants reported at any scheduled study visit starting with the first pre-dose safety visit (i.e., the first visit after informed consent and before the first administration of study drug) and continuing through the end of the treatment period. Relationship to the study treatment was determined using the standard categories defined in the protocol: Related (probably or possibly related); Unrelated (not related, unlikely related). Each AE was coded with MedDRA v24.0. The outcome reported is the study-wide total count of AEs in each relationship category.

    Time frame: From the first pre-dose safety visit to the end of the treatment period (e.g., 24 months post-dose) or the participant's last safety-assessment visit, whichever occurs later.

  4. Safety and Tolerability: White Blood Cell Count at Baseline, 12-month, and 24-month Post-infusion

    Clinical laboratory values for white blood cell (WBC) count at baseline, approximately 12 months and approximately 24 months post-infusion study visits. Results are summarized as mean (SD) across dosed participants with evaluable data at each timepoint.

    Time frame: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.

  5. Safety and Tolerability: Absolute Monocyte Count at Baseline, 12-month, and 24-month Post-infusion

    Clinical laboratory values for absolute monocyte count at baseline, approximately 12 months and approximately 24 months post-infusion study visits. Results are summarized as mean (SD) across dosed participants with evaluable data at each timepoint.

    Time frame: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.

  6. Safety and Tolerability: Platelet Count at Baseline, 12 Month and 24 Month Post-infusion

    Clinical laboratory values for platelet count at baseline, approximately 12 months and approximately 24 months post-infusion study visits. Results are summarized as mean (SD) across dosed participants with evaluable data at each timepoint.

    Time frame: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.

  7. Safety and Tolerability: Systolic and Diastolic Blood Pressure at Baseline, 12-month, and 24-month Post-infusion Study Visits

    Systolic and diastolic blood pressure at baseline, approximately 12 months and approximately 24 months post-infusion study visits. Measurements were taken with subjects positioned supine, seated, or semi-Fowler's position. Results are summarized as mean (SD) across dosed participants with evaluable data at each timepoint.

    Time frame: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.

  8. Safety and Tolerability: Heart Rate at Baseline, 12-month, and 24-month Post-infusion Study Visits

    Heart rate at baseline, approximately 12 months and approximately 24 months post-infusion study visits. Measurements were taken with subjects positioned supine, seated, or semi-Fowler's position. Results are summarized as mean (SD) across dosed participants with evaluable data at each timepoint.

    Time frame: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.

  9. Safety and Tolerability: Body Temperature at Baseline, 12-month, and 24-month Post-infusion Study Visits

    Body temperature at baseline, approximately 12 months, and approximately 24 months post-infusion study visits. Results are summarized as mean (SD) across dosed participants with evaluable data at each timepoint.

    Time frame: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.

  10. Safety and Tolerability: Respiratory Rate at Baseline, 12-month, and 24-month Post-infusion Study Visits

    Respiratory rate at baseline, approximately 12 months and approximately 24 months post-infusion study visits. Measurements were taken with subjects positioned supine, seated, or semi-Fowler's position. Results are summarized as mean (SD) across dosed participants with evaluable data at each timepoint.

    Time frame: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.

  11. Safety and Tolerability: Electrocardiogram (ECG) Ventricular Rates at Baseline, 12-month, and 24-month Post-infusion Study Visits

    Electrocardiogram (ECG) ventricular rate at baseline, approximately 12 months and approximately 24 months post-infusion study visits. ECG recordings were obtained using standard 12-lead resting ECGs. Results are summarized as mean (SD) across dosed participants with evaluable data at each timepoint.

    Time frame: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.

  12. Safety and Tolerability: Electrocardiogram (ECG) Intervals Including PR Interval, QRS Interval, QT Interval and QTc Bazett at Baseline, 12 Month and 24 Month Post-infusion Study Visits

    Electrocardiogram (ECG) intervals including PR interval, QRS interval, QT interval and QTc Bazett at baseline, approximately 12 months and approximately 24 months post-infusion study visits. ECG recordings were obtained using standard 12-lead resting ECGs. Results are summarized as mean (SD) across dosed participants with evaluable data at each timepoint.

    Time frame: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.

  13. Safety: Number of Dosed Participants Showing Evidence (Positive or Negative) of Genotoxicity as Determined by Polyclonal Expansion and Insertional Mutagenesis

    The number of dosed participants showing evidence (positive or negative) of polyclonal expansion and insertional mutagenesis as determined by vector integration site (VIS) analysis in whole blood collected at baseline and at approximately 1, 3, 6, 12, 18, and 24 months post-transplant. VIS analysis was performed using LTR-based PCR amplification and Illumina sequencing. Clonal abundance was monitored using the Sonic Abundance method.

    Time frame: Up to 24 months post-transplant

Secondary outcomes

  1. Efficacy: Cystine Levels in Leukocytes and Granulocytes at Baseline, 12 Month and 24 Month Post-infusion Study Visits

    Cystine levels in leukocytes and granulocytes from whole blood collected at baseline, approximately 12 months and approximately 24 months post-infusion study visits. Liquid chromatography tandem mass spectrometry (LC-MS/MS) using d4-cystine as an internal standard was used to measure cystine levels. Results are summarized as mean (SD) across dosed participants with evaluable data at each timepoint.

    Time frame: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.

  2. Efficacy: Clinical Laboratory Values of Estimated Glomerular Filtration Rate (eGFR) at Baseline, 12 Month and 24 Month Post-infusion Study Visits

    Estimated glomerular filtration rate (eGFR) calculated from creatinine in whole blood collected at baseline, approximately 12 months and approximately 24 months post-infusion using the 2021 CKD-EPI equation. This population included participants with native kidneys and participants with prior kidney transplantation. Results are summarized as mean (SD) across dosed participants with evaluable data at each timepoint.

    Time frame: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.

  3. Efficacy: Clinical Laboratory Values of Thyroxine (T4) Endocrine Levels at Baseline, 12 Month and 24 Month Post-infusion Study Visits

    Thyroxine (T4) hormone levels from whole blood collected at baseline, approximately 12 months and approximately 24 months post-infusion study visits. Results are summarized as mean (SD) across dosed participants with evaluable data at each timepoint. Normal reference range: 4.5-10.9 µg/dL.

    Time frame: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.

  4. Efficacy: Clinical Laboratory Values Thyroid-stimulating Hormone (TSH) Endocrine Levels at Baseline, 12 Month and 24 Month Post-infusion Study Visits

    Thyroid-stimulating hormone (TSH) levels from whole blood collected at baseline, approximately 12 months and approximately 24 months post-infusion study visits. Results are summarized as mean (SD) across dosed participants with evaluable data at each timepoint. Normal reference range: 0.27-4.2 µIU/mL.

    Time frame: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.

  5. Transduction Efficiency: Vector Copy Number (VCN) in Peripheral Blood at 12 Month and 24 Month Post-infusion Study Visits

    Vector copy number (VCN) in peripheral blood cells collected at approximately 12 months and approximately 24 months post-transplant to assess engraftment and transduction efficiency of gene-modified hematopoietic stem cells. VCN was measured by droplet digital PCR (ddPCR). Results are summarized as mean (SD) across dosed participants with evaluable data at each timepoint.

    Time frame: Approximately 12 months post-infusion and approximately 24 months post-infusion.

07

Results

Posted Aug 6, 2026
Limitations and caveats
Phase 1/2 open-label single-arm study; small sample size (n=6) limits statistical inference. Results descriptive, not generalizable to pediatric patients. Most adverse events were attributable to busulfan conditioning or underlying cystinosis. Individual participant data were not uploaded due to PRS technical limitations, but are available upon request. Statistical tests were performed per protocol; results are limited by the small sample size.

Participant flow

Subjects were recruited through ClinicalTrials.gov, the Cure Cystinosis International Registry, and cystinosis advocacy organization outreach, including national conferences. Eight subjects were screened; seven met eligibility criteria and were enrolled. Six subjects received CTNS-RD-04 infusion. One subject was a screen failure and one discontinued prior to dosing due to inadequate stem cell collection.

Participant flow — Overall Study
MilestoneGene Therapy With CTNS-RD-04 (Including Product Manufactured With and Without LentiBOOST)
Started7
Completed6
Not completed1
Withdrew: Inadequate stem cell collection following leukapheresis.1

Outcome measures

PrimarySafety and Tolerability: Total Number of Adverse Events (AEs) Per Participant (Pre- and Post-dose to End of Study)

The total count of all adverse events (AEs) recorded for each dosed participant reported at any scheduled study visit starting with the first pre-dose safety visit (i.e., the first visit after informed consent and before the first administration of study drug) and continuing through the end of the treatment period. Events were coded using MedDRA and graded according to NCI CTCAE criteria. The outcome is the total count of AEs per participant.

Time frame:
From the first pre-dose safety visit to the end of the treatment period (e.g., 24 months post-dose) or the participant's last safety-assessment visit, whichever occurs later.
Reported as:
Number · Adverse events per participant
Safety and Tolerability: Total Number of Adverse Events (AEs) Per Participant (Pre- and Post-dose to End of Study)
Adverse events per participantGene Therapy With CTNS-RD-04 (Including Product Manufactured With and Without LentiBOOST)
Patient 148
Patient 226
Patient 312
Patient 434
Patient 540
Patient 649
SecondaryEfficacy: Cystine Levels in Leukocytes and Granulocytes at Baseline, 12 Month and 24 Month Post-infusion Study Visits

Cystine levels in leukocytes and granulocytes from whole blood collected at baseline, approximately 12 months and approximately 24 months post-infusion study visits. Liquid chromatography tandem mass spectrometry (LC-MS/MS) using d4-cystine as an internal standard was used to measure cystine levels. Results are summarized as mean (SD) across dosed participants with evaluable data at each timepoint.

Time frame:
Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.
Reported as:
Mean · nmol half-cystine per mg protein
Efficacy: Cystine Levels in Leukocytes and Granulocytes at Baseline, 12 Month and 24 Month Post-infusion Study Visits
nmol half-cystine per mg proteinGene Therapy With CTNS-RD-04 (Including Product Manufactured With and Without LentiBOOST)
Leukocyte cystine - Baseline9.26 ± 5.71
Leukocyte cystine - 12 Months2.67 ± 0.79
Leukocyte cystine - 24 Months1.75 ± 0.84
Granulocyte cystine - Baseline10.22 ± 4.10
Granulocyte cystine - 12 Months5.07 ± 2.51
Granulocyte cystine - 24 Months4.26 ± 2.56
SecondaryEfficacy: Clinical Laboratory Values of Estimated Glomerular Filtration Rate (eGFR) at Baseline, 12 Month and 24 Month Post-infusion Study Visits

Estimated glomerular filtration rate (eGFR) calculated from creatinine in whole blood collected at baseline, approximately 12 months and approximately 24 months post-infusion using the 2021 CKD-EPI equation. This population included participants with native kidneys and participants with prior kidney transplantation. Results are summarized as mean (SD) across dosed participants with evaluable data at each timepoint.

Time frame:
Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.
Reported as:
Mean · mL/min/1.73 m²
Efficacy: Clinical Laboratory Values of Estimated Glomerular Filtration Rate (eGFR) at Baseline, 12 Month and 24 Month Post-infusion Study Visits
mL/min/1.73 m²Gene Therapy With CTNS-RD-04 (Including Product Manufactured With and Without LentiBOOST)
eGFR - Baseline69 ± 20
eGFR - 12 Months67 ± 22
eGFR - 24 Months59 ± 30
SecondaryEfficacy: Clinical Laboratory Values of Thyroxine (T4) Endocrine Levels at Baseline, 12 Month and 24 Month Post-infusion Study Visits

Thyroxine (T4) hormone levels from whole blood collected at baseline, approximately 12 months and approximately 24 months post-infusion study visits. Results are summarized as mean (SD) across dosed participants with evaluable data at each timepoint. Normal reference range: 4.5-10.9 µg/dL.

Time frame:
Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.
Reported as:
Mean · µg/dL
Efficacy: Clinical Laboratory Values of Thyroxine (T4) Endocrine Levels at Baseline, 12 Month and 24 Month Post-infusion Study Visits
µg/dLGene Therapy With CTNS-RD-04 (Including Product Manufactured With and Without LentiBOOST)
T4 - Baseline6.95 ± 0.92
T4 - 12 Months6.37 ± 0.72
T4 - 24 Months6.73 ± 1.30
SecondaryEfficacy: Clinical Laboratory Values Thyroid-stimulating Hormone (TSH) Endocrine Levels at Baseline, 12 Month and 24 Month Post-infusion Study Visits

Thyroid-stimulating hormone (TSH) levels from whole blood collected at baseline, approximately 12 months and approximately 24 months post-infusion study visits. Results are summarized as mean (SD) across dosed participants with evaluable data at each timepoint. Normal reference range: 0.27-4.2 µIU/mL.

Time frame:
Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.
Reported as:
Mean · µIU/mL
Efficacy: Clinical Laboratory Values Thyroid-stimulating Hormone (TSH) Endocrine Levels at Baseline, 12 Month and 24 Month Post-infusion Study Visits
µIU/mLGene Therapy With CTNS-RD-04 (Including Product Manufactured With and Without LentiBOOST)
TSH - Baseline2.86 ± 1.45
TSH - 12 Months3.74 ± 2.29
TSH - 24 Months4.93 ± 3.10
SecondaryTransduction Efficiency: Vector Copy Number (VCN) in Peripheral Blood at 12 Month and 24 Month Post-infusion Study Visits

Vector copy number (VCN) in peripheral blood cells collected at approximately 12 months and approximately 24 months post-transplant to assess engraftment and transduction efficiency of gene-modified hematopoietic stem cells. VCN was measured by droplet digital PCR (ddPCR). Results are summarized as mean (SD) across dosed participants with evaluable data at each timepoint.

Time frame:
Approximately 12 months post-infusion and approximately 24 months post-infusion.
Reported as:
Mean · Vector copy number per diploid genome
Transduction Efficiency: Vector Copy Number (VCN) in Peripheral Blood at 12 Month and 24 Month Post-infusion Study Visits
Vector copy number per diploid genomeGene Therapy With CTNS-RD-04 (Including Product Manufactured With and Without LentiBOOST)
VCN - Baseline0.00 ± 0.00
VCN - 12 Months1.46 ± 0.90
VCN - 24 Months1.30 ± 0.94
PrimarySafety and Tolerability: Aggregate Number of Adverse Events (AEs) by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Severity (Pre-dose and Post-dose to End of Study)

The total aggregate count of all graded adverse events (AEs) recorded for all dosed participants reported at any scheduled study visit starting with the first pre-dose safety visit (i.e., the first visit after informed consent and before the first administration of study drug) and continuing through the end of the treatment period. Events were coded using MedDRA v24.0 and graded according to NCI CTCAE version 4.03. The outcome is the total count of AEs per grade (Mild, Moderate, Severe, Life Threatening, Death).

Time frame:
From the first pre-dose safety visit to the end of the treatment period (e.g., 24 months post-dose) or the participant's last safety-assessment visit, whichever occurs later.
Reported as:
Number · Count (adverse events)
Safety and Tolerability: Aggregate Number of Adverse Events (AEs) by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Severity (Pre-dose and Post-dose to End of Study)
Count (adverse events)Gene Therapy With CTNS-RD-04 (Including Product Manufactured With and Without LentiBOOST)
Grade 1 (Mild)171
Grade 2 (Moderate)34
Grade 3 (Severe)4
Grade 4 (Life Threatening)0
Grade 5 (Fatal)0
PrimarySafety and Tolerability: Aggregate Number of Adverse Events (AEs) by Relationship to Study Treatment (Pre-dose and Post-dose to End of Study)

The total aggregate count of all adverse events (AEs) categorized by relationship to the study treatment recorded for all dosed participants reported at any scheduled study visit starting with the first pre-dose safety visit (i.e., the first visit after informed consent and before the first administration of study drug) and continuing through the end of the treatment period. Relationship to the study treatment was determined using the standard categories defined in the protocol: Related (probably or possibly related); Unrelated (not related, unlikely related). Each AE was coded with MedDRA v24.0. The outcome reported is the study-wide total count of AEs in each relationship category.

Time frame:
From the first pre-dose safety visit to the end of the treatment period (e.g., 24 months post-dose) or the participant's last safety-assessment visit, whichever occurs later.
Reported as:
Number · Adverse Events
Safety and Tolerability: Aggregate Number of Adverse Events (AEs) by Relationship to Study Treatment (Pre-dose and Post-dose to End of Study)
Adverse EventsGene Therapy With CTNS-RD-04 (Including Product Manufactured With and Without LentiBOOST)
Unrelated to study treatment (not related or unlikely related)209
Related to study treatment (possibly or probably)0
PrimarySafety and Tolerability: White Blood Cell Count at Baseline, 12-month, and 24-month Post-infusion

Clinical laboratory values for white blood cell (WBC) count at baseline, approximately 12 months and approximately 24 months post-infusion study visits. Results are summarized as mean (SD) across dosed participants with evaluable data at each timepoint.

Time frame:
Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.
Reported as:
Mean · 1000 cells/mm^3
Safety and Tolerability: White Blood Cell Count at Baseline, 12-month, and 24-month Post-infusion
1000 cells/mm^3Gene Therapy With CTNS-RD-04 (Including Product Manufactured With and Without LentiBOOST)
Baseline5.75 ± 1.72
12 Months4.43 ± 1.05
24 Months3.97 ± 0.84
PrimarySafety and Tolerability: Absolute Monocyte Count at Baseline, 12-month, and 24-month Post-infusion

Clinical laboratory values for absolute monocyte count at baseline, approximately 12 months and approximately 24 months post-infusion study visits. Results are summarized as mean (SD) across dosed participants with evaluable data at each timepoint.

Time frame:
Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.
Reported as:
Mean · 1000 cells/mm^3
Safety and Tolerability: Absolute Monocyte Count at Baseline, 12-month, and 24-month Post-infusion
1000 cells/mm^3Gene Therapy With CTNS-RD-04 (Including Product Manufactured With and Without LentiBOOST)
Baseline0.42 ± 0.16
12 Months0.33 ± 0.15
24 Months0.37 ± 0.15
PrimarySafety and Tolerability: Platelet Count at Baseline, 12 Month and 24 Month Post-infusion

Clinical laboratory values for platelet count at baseline, approximately 12 months and approximately 24 months post-infusion study visits. Results are summarized as mean (SD) across dosed participants with evaluable data at each timepoint.

Time frame:
Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.
Reported as:
Mean · 1000 cells/mm^3
Safety and Tolerability: Platelet Count at Baseline, 12 Month and 24 Month Post-infusion
1000 cells/mm^3Gene Therapy With CTNS-RD-04 (Including Product Manufactured With and Without LentiBOOST)
Baseline178 ± 74
12 Months148 ± 71
24 Months165 ± 74
PrimarySafety and Tolerability: Systolic and Diastolic Blood Pressure at Baseline, 12-month, and 24-month Post-infusion Study Visits

Systolic and diastolic blood pressure at baseline, approximately 12 months and approximately 24 months post-infusion study visits. Measurements were taken with subjects positioned supine, seated, or semi-Fowler's position. Results are summarized as mean (SD) across dosed participants with evaluable data at each timepoint.

Time frame:
Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.
Reported as:
Mean · mmHg
Safety and Tolerability: Systolic and Diastolic Blood Pressure at Baseline, 12-month, and 24-month Post-infusion Study Visits
mmHgGene Therapy With CTNS-RD-04 (Including Product Manufactured With and Without LentiBOOST)
Systolic - Baseline120.5 ± 13.7
Systolic - 12 Months114.5 ± 10.5
Systolic - 24 Months114.2 ± 12.4
Diastolic - Baseline76.2 ± 16.1
Diastolic - 12 Months74.8 ± 13.7
Diastolic - 24 Months66.0 ± 20.9
PrimarySafety and Tolerability: Heart Rate at Baseline, 12-month, and 24-month Post-infusion Study Visits

Heart rate at baseline, approximately 12 months and approximately 24 months post-infusion study visits. Measurements were taken with subjects positioned supine, seated, or semi-Fowler's position. Results are summarized as mean (SD) across dosed participants with evaluable data at each timepoint.

Time frame:
Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.
Reported as:
Mean · Beats per minute (BPM)
Safety and Tolerability: Heart Rate at Baseline, 12-month, and 24-month Post-infusion Study Visits
Beats per minute (BPM)Gene Therapy With CTNS-RD-04 (Including Product Manufactured With and Without LentiBOOST)
Vital signs HR - Baseline73.2 ± 11.9
Vital signs HR - 12 Months86.7 ± 11.2
Vital signs HR - 24 Months71.2 ± 3.1
PrimarySafety and Tolerability: Body Temperature at Baseline, 12-month, and 24-month Post-infusion Study Visits

Body temperature at baseline, approximately 12 months, and approximately 24 months post-infusion study visits. Results are summarized as mean (SD) across dosed participants with evaluable data at each timepoint.

Time frame:
Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.
Reported as:
Mean · Degrees Celsius
Safety and Tolerability: Body Temperature at Baseline, 12-month, and 24-month Post-infusion Study Visits
Degrees CelsiusGene Therapy With CTNS-RD-04 (Including Product Manufactured With and Without LentiBOOST)
Baseline36.47 ± 0.21
12 Months36.50 ± 0.21
24 Months36.50 ± 0.43
PrimarySafety and Tolerability: Respiratory Rate at Baseline, 12-month, and 24-month Post-infusion Study Visits

Respiratory rate at baseline, approximately 12 months and approximately 24 months post-infusion study visits. Measurements were taken with subjects positioned supine, seated, or semi-Fowler's position. Results are summarized as mean (SD) across dosed participants with evaluable data at each timepoint.

Time frame:
Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.
Reported as:
Mean · Breaths per minute
Safety and Tolerability: Respiratory Rate at Baseline, 12-month, and 24-month Post-infusion Study Visits
Breaths per minuteGene Therapy With CTNS-RD-04 (Including Product Manufactured With and Without LentiBOOST)
Baseline17 ± 1.7
12 Months16 ± 1.5
24 Months16 ± 2.7
PrimarySafety and Tolerability: Electrocardiogram (ECG) Ventricular Rates at Baseline, 12-month, and 24-month Post-infusion Study Visits

Electrocardiogram (ECG) ventricular rate at baseline, approximately 12 months and approximately 24 months post-infusion study visits. ECG recordings were obtained using standard 12-lead resting ECGs. Results are summarized as mean (SD) across dosed participants with evaluable data at each timepoint.

Time frame:
Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.
Reported as:
Mean · Beats per minute (BPM)
Safety and Tolerability: Electrocardiogram (ECG) Ventricular Rates at Baseline, 12-month, and 24-month Post-infusion Study Visits
Beats per minute (BPM)Gene Therapy With CTNS-RD-04 (Including Product Manufactured With and Without LentiBOOST)
ECG ventricular rate - Baseline71.3 ± 14.7
ECG ventricular rate - 12 Months74.2 ± 15.1
ECG ventricular rate - 24 Months66.8 ± 9.8
PrimarySafety and Tolerability: Electrocardiogram (ECG) Intervals Including PR Interval, QRS Interval, QT Interval and QTc Bazett at Baseline, 12 Month and 24 Month Post-infusion Study Visits

Electrocardiogram (ECG) intervals including PR interval, QRS interval, QT interval and QTc Bazett at baseline, approximately 12 months and approximately 24 months post-infusion study visits. ECG recordings were obtained using standard 12-lead resting ECGs. Results are summarized as mean (SD) across dosed participants with evaluable data at each timepoint.

Time frame:
Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.
Reported as:
Mean · Milliseconds (ms)
Safety and Tolerability: Electrocardiogram (ECG) Intervals Including PR Interval, QRS Interval, QT Interval and QTc Bazett at Baseline, 12 Month and 24 Month Post-infusion Study Visits
Milliseconds (ms)Gene Therapy With CTNS-RD-04 (Including Product Manufactured With and Without LentiBOOST)
PR interval - Baseline145.0 ± 29.9
PR interval - 12 Months149.7 ± 16.2
PR interval - 24 Months148.0 ± 18.4
QRS interval - Baseline90.3 ± 12.0
QRS interval - 12 Months88.0 ± 14.0
QRS interval - 24 Months88.3 ± 15.8
QT interval - Baseline390.0 ± 40.9
QT interval - 12 Months367.0 ± 29.7
QT interval - 24 Months411.3 ± 74.0
QTc (Bazett) - Baseline419.7 ± 23.1
QTc (Bazett) - 12 Months402.8 ± 18.4
QTc (Bazett) - 24 Months434.5 ± 102.0
PrimarySafety: Number of Dosed Participants Showing Evidence (Positive or Negative) of Genotoxicity as Determined by Polyclonal Expansion and Insertional Mutagenesis

The number of dosed participants showing evidence (positive or negative) of polyclonal expansion and insertional mutagenesis as determined by vector integration site (VIS) analysis in whole blood collected at baseline and at approximately 1, 3, 6, 12, 18, and 24 months post-transplant. VIS analysis was performed using LTR-based PCR amplification and Illumina sequencing. Clonal abundance was monitored using the Sonic Abundance method.

Time frame:
Up to 24 months post-transplant
Reported as:
Count of participants · Participants
Safety: Number of Dosed Participants Showing Evidence (Positive or Negative) of Genotoxicity as Determined by Polyclonal Expansion and Insertional Mutagenesis
ParticipantsGene Therapy With CTNS-RD-04 (Including Product Manufactured With and Without LentiBOOST)
No evidence of genotoxicity or insertional mutagenesis6
Evidence of genotoxicity or insertional mutagenesis0

Adverse events

Collected over From the first pre-dose safety assessment through approximately 24 months post-infusion, or the participant's last safety-assessment visit, whichever occurs later.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Gene Therapy With CTNS-RD-04 (Including Product Manufactured With and Without LentiBOOST)0/6 (0%)1/6 (16.7%)6/6 (100%)
Most frequent serious events
Most frequent serious events
EventGene Therapy With CTNS-RD-04 (Including Product Manufactured With and Without LentiBOOST)
Coronary artery stenosisCardiac disorders1/6
Most frequent other events
Showing 10 of 33
Most frequent other events
EventGene Therapy With CTNS-RD-04 (Including Product Manufactured With and Without LentiBOOST)
HypogonadismEndocrine disorders6/6
Oral mucositisGastrointestinal disorders6/6
AlopeciaSkin and subcutaneous tissue disorders6/6
RashSkin and subcutaneous tissue disorders6/6
ThrombocytopeniaBlood and lymphatic system disorders5/6
DiarrheaGastrointestinal disorders5/6
FatigueGeneral disorders5/6
Bone painMusculoskeletal and connective tissue disorders5/6
AzoospermiaReproductive system and breast disorders5/6
LeukopeniaBlood and lymphatic system disorders4/6

Baseline characteristics

Baseline characteristics were analyzed for all enrolled participants who entered the mobilization and leukapheresis period (n=7). This population corresponds to the participants assigned in the Participant Flow. One enrolled participant discontinued prior to conditioning and infusion; however, baseline data were collected prior to discontinuation and are included.

Age, Continuous
Age, Continuous(Years)Gene Therapy With CTNS-RD-04 (Including Product Manufactured With and Without LentiBOOST)
Mean28.0 ± 9.2
Sex: Female, Male
Sex: Female, Male(Participants)Gene Therapy With CTNS-RD-04 (Including Product Manufactured With and Without LentiBOOST)
Female2
Male5
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Gene Therapy With CTNS-RD-04 (Including Product Manufactured With and Without LentiBOOST)
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American0
White7
More than one race0
Unknown or Not Reported0
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Gene Therapy With CTNS-RD-04 (Including Product Manufactured With and Without LentiBOOST)
Hispanic or Latino0
Not Hispanic or Latino7
Unknown or Not Reported0
Baseline Estimated Glomerular Filtration Rate (eGFR), Continuous
Baseline Estimated Glomerular Filtration Rate (eGFR), Continuous(mL/min/1.73m2)Gene Therapy With CTNS-RD-04 (Including Product Manufactured With and Without LentiBOOST)
Mean64 ± 22
08

Study locations

1 site
  • University of California San Diego
    La Jolla, California 92093, United States
09

References and documents

Publications

  • Harrison F, Yeagy BA, Rocca CJ, Kohn DB, Salomon DR, Cherqui S. Hematopoietic stem cell gene therapy for the multisystemic lysosomal storage disorder cystinosis. Mol Ther. 2013 Feb;21(2):433-44. doi: 10.1038/mt.2012.214. Epub 2012 Oct 23. PubMed 23089735 ↗
  • Naphade S, Sharma J, Gaide Chevronnay HP, Shook MA, Yeagy BA, Rocca CJ, Ur SN, Lau AJ, Courtoy PJ, Cherqui S. Brief reports: Lysosomal cross-correction by hematopoietic stem cell-derived macrophages via tunneling nanotubes. Stem Cells. 2015 Jan;33(1):301-9. doi: 10.1002/stem.1835. PubMed 25186209 ↗
  • Afshari NA, Lee BJ, Borooah S, Nudleman E, Ahmed I, Sawyers A, Arias JM, Manalang N, Cherqui S. Comprehensive Ocular Characteristics in Cystinosis after Hematopoietic Stem-Cell Gene Therapy Over 24 Months. Am J Ophthalmol. 2026 May;285:288-299. doi: 10.1016/j.ajo.2026.01.038. Epub 2026 Feb 9. PubMed 41672367 ↗
  • Barshop BA, Ball ED, Benador N, Trauner D, Phillips S, Dohil R, Afshari NA, Roy S, Campo Fernandes B, Kohn D, Shayan K, Everett JK, Bushman FD, Midgley J, Liang H, Sawyers A, Gangoiti JA, Panchal M, Ahmed I, Cherqui S. Hematopoietic Stem-Cell Gene Therapy for Cystinosis. N Engl J Med. 2026 Feb 19;394(8):753-762. doi: 10.1056/NEJMoa2506431. PubMed 41707137 ↗

Study documents

  • Protocol and statistical analysis plan · Oct 25, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices).

Supporting information: Study protocol

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 6, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03897361
Lead sponsor
University of California, San Diego
Collaborators
California Institute for Regenerative Medicine (CIRM), Cystinosis Research Foundation
Responsible party
Stephanie Cherqui (Professor, University of California, San Diego) — Principal investigator
First posted
Apr 1, 2019
Start date
Jul 8, 2019
Primary completion
Sep 18, 2024
Completion
Sep 18, 2024
Results posted
Aug 6, 2026
Last update
Aug 6, 2026

Study contacts

Stephanie Cherqui, Ph.D.
principal investigator · University of California, San Diego

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Jul 2026. You cannot join it, but the record below documents what was studied.

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