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

NCT04443907 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: CADPT03A12101
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Sickle Cell Disease

Keywords

Gene therapy; genome-edited hematopoietic stem and progenitor cellular therapy; sickle cell; autologous transplant; BCL11A

Outcome Measures

Primary Outcomes (3)

• 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.

  up to 24 months

• 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.

  at 6 months

• 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.

  up to 24 months

Secondary Outcomes (15)

• Durability of hematologic engraftment

  up to 24 months

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

  12 months

• Time to achieve 30% total HbF

  up to 24 months

• Time to peak total HbF

  up to 24 months

• Percentage of edited WBC and bone marrow cells by time points

  up to 24 months

Study Arms (1)

OTQ923

EXPERIMENTAL

Single 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.

Biological: OTQ923

Interventions

OTQ923 BIOLOGICAL

Single intravenous infusion of OTQ923 cell suspension

Also known as: Adult Part A

OTQ923

Eligibility Criteria

• Age: 2 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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
• Protocol defined iron overload
• Cerebrovascular procedure within one year, including pial synangiosis for Moyamoya
• Severe or progressive arteriopathy or cerebrovascular disease, including Moyamoya

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (3)

University of Chicago

Chicago, Illinois, 60637, United States

Location

Memorial Sloan Kettering Cancer Ctr

New York, New York, 10065, United States

Location

St Jude Children's Research Hospital

Memphis, Tennessee, 38105-3678, United States

Location

Related Publications (5)

• 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.

  PMID: 38866240 DERIVED

• 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.

  PMID: 37646679 DERIVED

• 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.

  PMID: 36975201 DERIVED

• 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.

  PMID: 36860093 DERIVED

• 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.

  PMID: 36123234 DERIVED

Related Links

• CADPT03A12101 Clinical Trial Results Form
• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Anemia, Sickle Cell

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: The is an open-label study.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2020
• First Posted: June 23, 2020
• Study Start: August 25, 2020
• Primary Completion: January 6, 2025
• Study Completion: January 6, 2025
• Last Updated: January 8, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)