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The decision of early termination was made due to business reasons and was not a consequence of any safety concern.
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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.
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:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| OTQ923 | Biological | Single intravenous infusion of OTQ923 cell suspension |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | up to 24 months |
| Proportion of subject to achieve 30% of total HbF at 12 months |
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Inclusion Criteria:
Exclusion Criteria:
Other protocol defined inclusion/exclusion criteria may apply
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Chicago | Chicago | Illinois | 60637 | United States | ||
| Memorial Sloan Kettering Cancer Ctr |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38866240 | Derived | 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. | |
| 37646679 | Derived |
| Label | URL |
|---|---|
| CADPT03A12101 Clinical Trial Results Form | View source |
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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
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| ID | Term |
|---|---|
| D000755 | Anemia, Sickle Cell |
| ID | Term |
|---|---|
| D000745 | Anemia, Hemolytic, Congenital |
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
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The is an open-label study.
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| OTQ923 | Biological | Single intravenous infusion of OTQ923, based on review of data from Part A by Health agencies after a formal interim analysis |
|
|
Assessment of HbF expression will be done by measuring total fetal hemoglobin over time. |
| 12 months |
| Time to achieve 30% total HbF | Assessment of HbF expression will be done by measuring total fetal hemoglobin over time. | up to 24 months |
| Time to peak total HbF | Assessment of HbF expression will be done by measuring total fetal hemoglobin over time. | up to 24 months |
| Percentage of edited WBC and bone marrow cells by time points | Assessment of in vivo cellular kinetics | up to 24 months |
| 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 | up to 24 months |
| 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. | up to 24 months |
| Transplant-related mortality | Assessment of mortality | up to 24 months |
| 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 | up to 24 months |
| 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. | Baseline, 12 months |
| 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. | Bseline, 12 months |
| 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 | up to 24 months |
| 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 | up to 24 months |
| 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 | up to 24 months |
| 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 | up to 24 months |
| New York |
| New York |
| 10065 |
| United States |
| St Jude Children's Research Hospital | Memphis | Tennessee | 38105-3678 | United States |
| 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. |
| 36975201 | 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. |
| 36860093 | 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. |
| 36123234 | 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. |
| A Plain Language Trial Summary is available on www.novctrd.com | View source |
| D006425 |
| Hemic and Lymphatic Diseases |
| D006453 | Hemoglobinopathies |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |