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Sickle Cell DiseasePhase 1NCT04443907

Study of Safety and Efficacy of Genome-edited Hematopoietic Stem and Progenitor Cells in Sickle Cell Disease (SCD)

A Phase 1 study testing OTQ923 in people with Sickle Cell Disease, run by Novartis Pharmaceuticals at 3 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This study evaluated a genome-edited, autologous, hematopoietic stem and progenitor cell (HSPC) product - OTQ923 to reduce the biologic activity of BCL11A, increasing fetal hemoglobin (HbF) and reducing complications of sickle cell disease. Read more about this study

Who is it for?
Ages 2 to 40 years
Conditions the study is for
Sickle Cell Disease
What is being tested?
OTQ923
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4 participants
Where
3 sitesUnited States
Study dates
25 Aug 2020to 6 Jan 2025
Phase
Phase 1
Are there results?
None posted in the registry

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 2 to 40 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Male or female subjects age 2-40 years inclusive
  • Confirmed diagnosis of sickle cell disease with globin typing (e.g. HbSS, HbSC, HbS/β0-thalassemia or others)
  • Performance status >70% (Karnofsky for subjects >16 years of age and Lansky for subjects <16 years of age)
  • At least one of the following indicators of disease severity as defined in the protocol - Vaso-occlusive pain crisis, Acute chest syndrome, Recurrent priapism, prior stroke, receive chronic transfusions, Red cell alloimmunization
  • Subjects, who have failed, not tolerated or refused hydroxyurea therapy.

Who cannot join

  • Available matched related donor for HSCT
  • Clinically significant active infection
  • Seropositive for HIV or HTLV
  • Active known malignancy, myelodysplasia, abnormal cytogenetics or immunodeficiency
  • Prior HSCT or gene therapy
  • Known hepatic cirrhosis, bridging hepatic fibrosis or active hepatitis
Show all 10Show fewer
  • Protocol defined iron overload
  • Cerebrovascular procedure within one year, including pial synangiosis for Moyamoya
  • Severe or progressive arteriopathy or cerebrovascular disease, including Moyamoya
  • Other protocol defined inclusion/exclusion criteria may apply

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • University of Chicago

    Chicago, Illinois, 60637

  • St Jude Children's Research Hospital

    Memphis, Tennessee, 38105-3678

  • Memorial Sloan Kettering Cancer Ctr

    New York, New York, 10065

Other trials in United States

About this study

Official title: A First-in-patient Phase I/II Clinical Study to Investigate the Safety, Tolerability and Efficacy of Genome-edited Hematopoietic Stem and Progenitor Cells in Subjects With Severe Complications of Sickle Cell Disease

This study evaluated a genome-edited, autologous, hematopoietic stem and progenitor cell (HSPC) product - OTQ923 to reduce the biologic activity of BCL11A, increasing fetal hemoglobin (HbF) and reducing complications of sickle cell disease.

Read the detailed description

CADPT03A12101 was a multicenter, multi-part, first-in-human, proof-of-concept, open label non-randomized, clinical study in Sickle Cell Disease (SCD) subjects. This study included apheresis of mobilized hematopoietic stem and progenitor cells (HSPCs), ex vivo CRISPR/Cas9-mediated genome editing and expansion, followed by myeloablative conditioning and autologous hematopoietic stem cell transplant (HSCT) with follow-up for a minimum of one year and up to two years.

The study was divided into the following parts:

  • Part A - Adult subjects were dosed with OTQ923.
  • Part B - Assessment of OTQ923 in pediatric patients, however Part B was not opened.
Being tested
OTQ923
Keywords
Gene therapy, genome-edited hematopoietic stem and progenitor cellular therapy, sickle cell, autologous transplant, BCL11A
Medical subject headings
Anemia, Sickle Cell

What participants receive

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

  • OTQ923Biological

    Also called Adult Part A

    Single intravenous infusion of OTQ923 cell suspension

  • OTQ923Biological

    Also called Children 2-17 years old - Part B

    Single intravenous infusion of OTQ923, based on review of data from Part A by Health agencies after a formal interim analysis

Study groups in NCT04443907
Study groupRoleWhat they receive
OTQ923ExperimentalSingle intravenous infusion of OTQ923 Part A - Adults treated with OTQ923; Part B - Children age 2-17 treated with OTQ923 based on review of data from Part A by Health agency after a formal interim analysis.
Receives: Biological: OTQ923

What is being measured

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

  1. Number of participants with adverse events and serious adverse events

    Number of participants with adverse events (AEs) and serious adverse events (SAEs), including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs.

    Measured: up to 24 months

  2. Fetal hemoglobin (HbF) expression 6 months after hematopoietic stem cell transplant (HSCT)

    Assessment of HbF expression will be done by measuring total fetal hemoglobin over time.

    Measured: at 6 months

  3. Time to reach absolute neutrophil count (ANC) ≥500/μL for 3 consecutive days

    Time to engraftment is defined as first of 3 consecutive days when an absolute neutrophil count (ANC) ≥500/μL after receiving OTQ923 was reached.

    Measured: up to 24 months

Secondary outcomes (15)

  1. Durability of hematologic engraftment

    Engraftment durability/persistence by measuring the proportion of alleles with on-target CRISPR modification in peripheral blood (total white blood cells (WBC)) and bone marrow over time up to 24 months

    Measured: up to 24 months

  2. Proportion of subject to achieve 30% of total HbF at 12 months

    Assessment of HbF expression will be done by measuring total fetal hemoglobin over time.

    Measured: 12 months

  3. Time to achieve 30% total HbF

    Assessment of HbF expression will be done by measuring total fetal hemoglobin over time.

    Measured: up to 24 months

  4. Time to peak total HbF

    Assessment of HbF expression will be done by measuring total fetal hemoglobin over time.

    Measured: up to 24 months

  5. Percentage of edited WBC and bone marrow cells by time points

    Assessment of in vivo cellular kinetics

    Measured: up to 24 months

  6. Number of participants with treatment induced anti-Cas9 humoral and cellular immunogenicity

    To evaluate presence of pre-existing or treatment induced anti-Cas9 humoral and cellular immunogenicity

    Measured: up to 24 months

  7. Overall Survival

    To evaluate the overall survival which is defined as the time from date of start of treatment to date of death to any cause.

    Measured: up to 24 months

  8. Transplant-related mortality

    Assessment of mortality

    Measured: up to 24 months

  9. Evaluation of effect on patient-reported outcomes from baseline and post-HSCT with age appropriate patient reported measures

    Determine health status following instruments ASCQ-ME emotional impact

    Measured: up to 24 months

  10. Number of participants with change from baseline of annualized VOC rate by 65%

    The annualized rate at baseline will be compared to that of vaso-occlusive crises (VOC) at 12 months.

    Measured: Baseline, 12 months

  11. Number of participants with change from baseline of annualized SCD complications (aggregate of VOC, ACS, priapism and stroke) and if relevant, rate of transfusion by 65%

    The annualized rate at baseline will be compared to that of aggregate Sickle Cell Disease (SCD) complications (VOC, acute chest syndrome (ACS), priapism, and stroke) and transfusions at 12 months.

    Measured: Bseline, 12 months

  12. Evaluation of effect on patient-reported outcomes from baseline and post-HSCT with age appropriate patient reported measures

    Determine health status following instruments PROMIS fatique

    Measured: up to 24 months

  13. Evaluation of effect on patient-reported outcomes from baseline and post-HSCT with age appropriate patient reported measures

    Determine health status following instruments PROMIS physical functioning

    Measured: up to 24 months

  14. Evaluation of effect on patient-reported outcomes from baseline and post-HSCT with age appropriate patient reported measures

    Determine health status following instruments ASCQ-ME sleep impact

    Measured: up to 24 months

  15. Evaluation of effect on patient-reported outcomes from baseline and post-HSCT with age appropriate patient reported measures

    Determine health status following instruments ASCQ-ME pain impact

    Measured: up to 24 months

Timeline

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

  1. First posted23 Jun 2020
  2. Study start25 Aug 2020
  3. Primary completion6 Jan 2025
  4. Study completion6 Jan 2025

Why it stopped: The decision of early termination was made due to business reasons and was not a consequence of any safety concern.

Resources

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04443907
Sponsor's protocol ID
CADPT03A12101
Status last verified
Jan 2026
First submitted
29 Apr 2020
Last updated
8 Jan 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Publications

  • Ligon JA, Cupit-Link MC, Yu C, Levine J, Foley T, Rotz S, Sharma A, Gomez-Lobo V, Shah NN. Pediatric Cancer Immunotherapy and Potential for Impact on Fertility: A Need for Evidence-Based Guidance. Transplant Cell Ther. 2024 Aug;30(8):737-749. doi: 10.1016/j.jtct.2024.06.006. Epub 2024 Jun 10.

    PubMed 38866240

  • Sharma A, Boelens JJ, Cancio M, Hankins JS, Bhad P, Azizy M, Lewandowski A, Zhao X, Chitnis S, Peddinti R, Zheng Y, Kapoor N, Ciceri F, Maclachlan T, Yang Y, Liu Y, Yuan J, Naumann U, Yu VWC, Stevenson SC, De Vita S, LaBelle JL. CRISPR-Cas9 Editing of the HBG1 and HBG2 Promoters to Treat Sickle Cell Disease. N Engl J Med. 2023 Aug 31;389(9):820-832. doi: 10.1056/NEJMoa2215643.

    PubMed 37646679

  • Sharma A, Young A, Carroll Y, Darji H, Li Y, Mandrell BN, Nelson MN, Owens CL, Irvine M, Caples M, Jerkins LP, Unguru Y, Hankins JS, Johnson LM. Gene therapy in sickle cell disease: Attitudes and informational needs of patients and caregivers. Pediatr Blood Cancer. 2023 Jun;70(6):e30319. doi: 10.1002/pbc.30319. Epub 2023 Mar 28.

    PubMed 36975201

  • Persaud Y, Mandrell BN, Sharma A, Carroll Y, Irvine M, Olufadi Y, Kang G, Hijano DR, Rai P, Hankins JS, Johnson LM. Attitudes toward COVID-19 vaccine among pediatric patients with sickle cell disease and their caregivers. Pediatr Blood Cancer. 2023 May;70(5):e30274. doi: 10.1002/pbc.30274. Epub 2023 Mar 1.

    PubMed 36860093

  • Bhoopalan SV, Yen JS, Levine RM, Sharma A. Editing human hematopoietic stem cells: advances and challenges. Cytotherapy. 2023 Mar;25(3):261-269. doi: 10.1016/j.jcyt.2022.08.003. Epub 2022 Sep 17.

    PubMed 36123234

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing OTQ923 in people with Sickle Cell Disease, run by Novartis Pharmaceuticals at 3 sites in United States.

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 5 inclusion and 10 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: stopped early, as of the sponsor's last update on 8 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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 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.

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

Are results available for this study?

The study was stopped early (reason given: The decision of early termination was made due to business reasons and was not a consequence of any safety concern.). Results are not available in the source record.

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?

Number of participants with adverse events and serious adverse events (time frame: up to 24 months). The study lists 3 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 NCT04443907, which also lists 5 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 8 Jan 2026.

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