Lysosomal Storage DiseasesPhase 1/2NCT03897361

Stem Cell Gene Therapy for Cystinosis

A Phase 1/2 study testing CTNS-RD-04 (including CTNS-RD-04-LB manufactured with LentiBOOST) in people with Lysosomal Storage Diseases and Cystinosis, run by University of California, San Diego at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Lysosomal Storage Diseases, Cystinosis
What is being tested?: CTNS-RD-04 (including CTNS-RD-04-LB manufactured with LentiBOOST)
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 7 participants
Where: 1 siteUnited States
Study dates: 8 Jul 2019to 18 Sep 2024
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

The following criteria must be met by all subjects considered for study participation.
Cohorts 1 and 2: Male or female subject is ≥ 18 years of age.
Cohort 3: Male or female subject is ≥ 14 years of age.
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.
Subject has a Karnofsky Performance Status or age-dependent Lansky Performance of ≥ 60.
If subject has had a kidney transplant, he or she must be at least one-year post kidney transplant status.

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Subject has adequate hematologic function:
Absolute neutrophil count (ANC) ≥ 1.5 x 1000/mm^3
Platelet count ≥ 100 x 1000/mm^3
Hemoglobin ≥ 9.0 gm/dL
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 an adequate renal function:
Serum creatinine <2x ULN mg/dL
Subject has adequate coagulation:
PT/aPTT ≤ 1.2 x ULN seconds
INR ≤ 2
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
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.
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.
Subject is willing and able to comply with the study restrictions and requirements.
Subject is willing to provide written informed consent/permission/assent prior to participation in the study.
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.
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.
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).

Who cannot join

Subject has an active, uncontrolled, acute bacterial, viral, or fungal infection during screening or within 30 days prior to starting the conditioning regimen.
Subject has positive serology at screening for any of the following:
Human Immunodeficiency Virus (HIV) 1-2
Human T-cell Lymphotropic Virus (HTLV) - I/II
Hepatitis B core and Hepatitis B PCR positive
Hepatitis C Virus (HCV)

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Rapid Plasma Reagin (RPR)
Chagas' Disease (T. curzi)
QuantiferonTB
Nucleic Acid Test (NAT) for HIV
West Nile Virus (WNV)
Subject has a known clinically significant immunodeficiency disorder.
Subject is a female of childbearing potential that is nursing, planning a pregnancy or has a positive serum pregnancy test.
Subject has received a prior marrow or stem cell transplantation or is planning to receive one within 90 days of study initiation.
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.
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).
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.
Subject has impaired pulmonary function (based on FEV1 of <=50% of predicted or DLCO of <=40 % of predicted and gender-specific normal threshold value).
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).
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.
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.
Subject has a known history of drug or alcohol addiction.
Subject has undergone major surgery within 90 days (or longer if not fully recovered) prior to screening.
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 previously received gene therapy at any time.
Subject is currently receiving or anticipates receiving another investigational agent, device, or procedure from 30 days prior to screening through study completion.
Subject has any condition, in the opinion of the investigator, that compromises compliance with study requirements.

Trial locations and contacts

1 site in 1 country.

United States1 site

University of California San Diego
La Jolla, California, 92093

Other trials in United States

About this study

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 and Will Include Transduction Enhancer When Required During Manufacturing

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.

Conditions: Lysosomal Storage Diseases, Cystinosis
Being tested: CTNS-RD-04 (including CTNS-RD-04-LB manufactured with LentiBOOST)
Keywords: Cystinosis, Lysosomal Storage Disorders, LSD
Medical subject headings: Lysosomal Storage Diseases, Cystinosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT03897361
Study group	Role	What they receive
Gene Therapy with CTNS-RD-04 (including product manufactured with and without LentiBOOST)	Experimental	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. Receives: Genetic: CTNS-RD-04 (including CTNS-RD-04-LB manufactured with LentiBOOST)

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
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).
Measured: 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.
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.
Measured: 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.
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.
Measured: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.
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.
Measured: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.
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.
Measured: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.
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.
Measured: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.
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.
Measured: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.
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.
Measured: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.
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.
Measured: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.
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.
Measured: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.
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.
Measured: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.
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.
Measured: Up to 24 months post-transplant

Secondary outcomes (5)

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.
Measured: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.
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.
Measured: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.
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.
Measured: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.
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.
Measured: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.
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.
Measured: Approximately 12 months post-infusion and approximately 24 months post-infusion.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

8 Jul 201918 Sep 2024

First posted1 Apr 2019
Study start8 Jul 2019
Primary completion18 Sep 2024
Study completion18 Sep 2024

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Lysosomal Storage DiseasesStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Model description: This study will include up to 6 subjects to be dosed and follow 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)
Enrolment: 7 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03897361
Sponsor's protocol ID: 018631
Status last verified: Jul 2026
First submitted: 6 Feb 2019
Last updated: 6 Aug 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices).

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

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 6 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

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 and Will Include Transduction Enhancer When Required During Manufacturing
ClinicalTrials.gov ID: NCT03897361
Acronym / sponsor ID: 018631
Conditions: Lysosomal Storage Diseases, Cystinosis
Keywords: Cystinosis, Lysosomal Storage Disorders, LSD
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 7 participants (actual)
Lead sponsor: University of California, San DiegoUniversity, hospital or other
Collaborators: California Institute for Regenerative Medicine (CIRM), Cystinosis Research Foundation
Study start: 8 Jul 2019 (actual)
Primary completion: 18 Sep 2024 (actual)
Study completion: 18 Sep 2024 (actual)
First posted: 1 Apr 2019 (actual)
Results: Posted 6 Aug 2026

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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 design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: This study will include up to 6 subjects to be dosed and follow 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).

Arm	Type	Receives
Gene Therapy with CTNS-RD-04 (including product manufactured with and without LentiBOOST)	Experimental	Genetic: CTNS-RD-04 (including CTNS-RD-04-LB manufactured with 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (30 listed)

The following criteria must be met by all subjects considered for study participation.
Cohorts 1 and 2: Male or female subject is ≥ 18 years of age.
Cohort 3: Male or female subject is ≥ 14 years of age.
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.
Subject has a Karnofsky Performance Status or age-dependent Lansky Performance of ≥ 60.

Key exclusion criteria (32 listed)

Subject has an active, uncontrolled, acute bacterial, viral, or fungal infection during screening or within 30 days prior to starting the conditioning regimen.
Subject has positive serology at screening for any of the following:
Subject has a known clinically significant immunodeficiency disorder.
Subject is a female of childbearing potential that is nursing, planning a pregnancy or has a positive serum pregnancy test.
Subject has received a prior marrow or stem cell transplantation or is planning to receive one within 90 days of study initiation.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CTNS-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.	Genetic	Gene Therapy with CTNS-RD-04 (including product manufactured with and without LentiBOOST)

Primary outcome

Safety and Tolerability: Total Number of Adverse Events (AEs) Per Participant (Pre- and Post-dose to End of Study)
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.
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.
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)
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.
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).
Safety and Tolerability: Aggregate Number of Adverse Events (AEs) by Relationship to Study Treatment (Pre-dose and Post-dose to End of Study)
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.
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.
Safety and Tolerability: White Blood Cell Count at Baseline, 12-month, and 24-month Post-infusion
Time frame: Baseline, approximately 12 months post-infusion, and approximately 24 months 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.
Safety and Tolerability: Absolute Monocyte Count at Baseline, 12-month, and 24-month Post-infusion
Time frame: Baseline, approximately 12 months post-infusion, and approximately 24 months 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.
Safety and Tolerability: Platelet Count at Baseline, 12 Month and 24 Month Post-infusion
Time frame: Baseline, approximately 12 months post-infusion, and approximately 24 months 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.
Safety and Tolerability: Systolic and Diastolic Blood Pressure at Baseline, 12-month, and 24-month Post-infusion Study Visits
Time frame: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.
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.
Safety and Tolerability: Heart Rate at Baseline, 12-month, and 24-month Post-infusion Study Visits
Time frame: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.
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.
Safety and Tolerability: Body Temperature at Baseline, 12-month, and 24-month Post-infusion Study Visits
Time frame: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.
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.
Safety and Tolerability: Respiratory Rate at Baseline, 12-month, and 24-month Post-infusion Study Visits
Time frame: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.
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.
Safety and Tolerability: Electrocardiogram (ECG) Ventricular Rates at Baseline, 12-month, and 24-month Post-infusion Study Visits
Time frame: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.
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.
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
Time frame: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.
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.
Safety: Number of Dosed Participants Showing Evidence (Positive or Negative) of Genotoxicity as Determined by Polyclonal Expansion and Insertional Mutagenesis
Time frame: Up to 24 months post-transplant
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.

5 secondary outcomes

Efficacy: Cystine Levels in Leukocytes and Granulocytes at Baseline, 12 Month and 24 Month Post-infusion Study Visits
Time frame: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.
Efficacy: Clinical Laboratory Values of Estimated Glomerular Filtration Rate (eGFR) at Baseline, 12 Month and 24 Month Post-infusion Study Visits
Time frame: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.
Efficacy: Clinical Laboratory Values of Thyroxine (T4) Endocrine Levels at Baseline, 12 Month and 24 Month Post-infusion Study Visits
Time frame: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.
Efficacy: Clinical Laboratory Values Thyroid-stimulating Hormone (TSH) Endocrine Levels at Baseline, 12 Month and 24 Month Post-infusion Study Visits
Time frame: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.
Transduction Efficiency: Vector Copy Number (VCN) in Peripheral Blood at 12 Month and 24 Month Post-infusion Study Visits
Time frame: Approximately 12 months post-infusion and approximately 24 months post-infusion.

Results and safety

Results posted to the registry on 6 Aug 2026, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Gene Therapy With CTNS-RD-04 (Including Product Manufactured With and Without LentiBOOST)	7	6

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

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.. Number. Unit: Adverse events per participant

Measure	Gene Therapy With CTNS-RD-04 (Including Product Manufactured With and Without LentiBOOST) n = 6
Patient 1	48
Patient 2	26
Patient 3	12
Patient 4	34
Patient 5	40
Patient 6	49

Population analysed: All dosed participants (n=6) are included. Total AEs per participant ranged from 12 to 49 events; aggregate total was 209 across all 6 participants.

Primary outcome: 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)

Measure	Gene Therapy With CTNS-RD-04 (Including Product Manufactured With and Without LentiBOOST) n = 6
Grade 1 (Mild)	171
Grade 2 (Moderate)	34
Grade 3 (Severe)	4
Grade 4 (Life Threatening)	0
Grade 5 (Fatal)	0

Population analysed: All dosed participants (n=6) are included. Seven participants entered the mobilization and leukapheresis period; one participant was discontinued prior to conditioning and infusion due to inadequate stem cell collection and did not receive CTNS-RD-04. This participant was not included in safety or efficacy analyses.

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

Measure	Gene Therapy With CTNS-RD-04 (Including Product Manufactured With and Without LentiBOOST) n = 6
Unrelated to study treatment (not related or unlikely related)	209
Related to study treatment (possibly or probably)	0

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

Time frame: Baseline, approximately 12 months post-infusion, and approximately 24 months post-infusion.. Mean (Standard Deviation). Unit: 1000 cells/mm^3

Measure	Gene Therapy With CTNS-RD-04 (Including Product Manufactured With and Without LentiBOOST) n = 6
Baseline	5.75 (1.72)
12 Months	4.43 (1.05)
24 Months	3.97 (0.84)

Population analysed: All dosed participants (n=6) are included. One participant was discontinued prior to conditioning and infusion and is not included. Results are summarized as mean (SD) at baseline, approximately 12 months, and approximately 24 months post-infusion. Evaluable data at each timepoint are included in the analysis.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: From the first pre-dose safety assessment through approximately 24 months post-infusion, or the participant's last safety-assessment visit, whichever occurs later.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Gene Therapy With CTNS-RD-04 (Including Product Manufactured With and Without LentiBOOST)	1 of 6 (16.7%)	6 of 6 (100%)	0 of 6

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 23089735Harrison 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.
Background: PubMed 25186209Naphade 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.
Results publication: PubMed 41672367Afshari 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.
Results publication: PubMed 41707137Barshop 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.
Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices).

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Stephanie Cherqui, Ph.D. principal investigator

University of California, San Diego

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 30 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Aug 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and Tolerability: Total Number of Adverse Events (AEs) Per Participant (Pre- and Post-dose to End of Study) (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.). The study lists 13 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03897361, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2026; AzTrials last refreshed its copy on 30 Oct 2026.