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| Name | Class |
|---|---|
| CRISPR Therapeutics | INDUSTRY |
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This is a single-arm, open-label, multi-site, single-dose Phase 1/2/3 study in subjects with severe sickle cell disease (SCD). The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (hHSPCs) using CTX001.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CTX001 | Experimental | CTX001 (autologous CD34+ hHSPCs modified with CRISPR-Cas9 at the erythroid lineage-specific enhancer of the BCL11A gene). Subjects will receive a single infusion of CTX001 through a central venous catheter. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CTX001 | Biological | Administered by IV infusion following myeloablative conditioning with busulfan. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of subjects who have not experienced any severe vaso-occlusive crisis (VOC) for at least 12 consecutive months (VF12) | From 60 days after last RBC transfusion up to 2 years after CTX001 infusion | |
| Proportion of subjects with engraftment (first day of three consecutive measurements of absolute neutrophil count [ANC] ≥500/µL on three different days) | Within 42 days after CTX001 infusion | |
| Time to engraftment | From CTX001 infusion up to 2 years after CTX001 infusion | |
| Frequency and severity of collected adverse events (AEs) | From screening to 2 years after CTX001 infusion | |
| Incidence of transplant-related mortality (TRM) within 100 days after CTX001 infusion | Within 100 days after CTX001 infusion | |
| Incidence of TRM within 1 year after CTX001 infusion | Within 1 year after CTX001 infusion | |
| All-cause mortality | 2 years after mobilization |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of subjects free from inpatient hospitalization for severe VOCs sustained for at least 12 months (HF12) | From 60 days after last RBC transfusion up to 2 years after CTX001 infusion | |
| Proportion of subjects who have not experienced any severe VOC for at least 9 consecutive months (VF9) any time after CTX001 infusion |
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Key Inclusion Criteria:
Key Exclusion Criteria:
Other protocol defined inclusion/exclusion criteria may apply
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Lucile Packard Children's Hospital of Stanford University | Palo Alto | California | 94304 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40857358 | Derived | Sharma A, Locatelli F, Bhatia M, Molinari L, Mapara MY, Liem RI, Dedeken L, Wall D, Eckrich MJ, Kuo KHM, Smith W, Imren S, Kohli P, Li N, Liu T, Rubin J, Hobbs W, Grupp SA, Frangoul H. Improvements in health-related quality of life in patients with severe sickle cell disease after exagamglogene autotemcel. Blood Adv. 2025 Dec 23;9(24):6481-6490. doi: 10.1182/bloodadvances.2025016701. | |
| 38866240 |
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| From 60 days after last RBC transfusion up to 2 years after CTX001 infusion |
| Proportion of subjects with 90 percent (%), 80%, 75% or 50% reduction in annualized rate of severe VOCs | From 60 days after last RBC transfusion up to 2 years after CTX001 infusion |
| Relative change from baseline in annualized rate of severe VOCs | From 60 days after last RBC transfusion up to 2 years after CTX001 infusion |
| Duration of severe VOC free in subjects who have achieved VF12 | From 60 days after last RBC transfusion up to 2 years after CTX001 infusion |
| Relative Change from baseline in rate of inpatient hospitalization for severe VOCs | From 60 days after last RBC transfusion up to 2 years after CTX001 infusion |
| Relative change from baseline in annualized duration of hospitalization for severe VOCs | From 60 days after last RBC transfusion up to 2 years after CTX001 infusion |
| Proportion of subjects with sustained HbF ≥20% for at least 3 months | From 60 days after last RBC transfusion up to 2 years after CTX001 infusion |
| Proportion of subjects with sustained HbF ≥20% for at least 12 months | From 60 days after last RBC transfusion up to 2 years after CTX001 infusion |
| Proportion of subjects with sustained HbF ≥20% for at least 6 months | From 60 days after last RBC transfusion up to 2 years after CTX001 infusion |
| Change in number of units of RBC transfused for SCD-related indications | 6 months up to 2 years after CTX001 infusion |
| HbF concentration over time | 1 month up to 2 years after CTX001 infusion |
| Hb concentration over time | From the time of CTX001 up to 2 years after CTX001 infusion |
| Change from baseline in indirect bilirubin over time | From baseline (pre-infusion) up to 2 years after CTX001 infusion |
| Change from baseline in reticulocyte count over time | From baseline (pre-infusion) up to 2 years after CTX001 infusion |
| Change from baseline in haptoglobin over time | From baseline (pre-infusion) up to 2 years after CTX001 infusion |
| Change from baseline in lactate dehydrogenase over time | From baseline (pre-infusion) up to 2 years after CTX001 infusion |
| Proportion of alleles with intended genetic modification present in peripheral blood leukocytes over time | 1 month up to 2 years after CTX001 infusion |
| Proportion of alleles with intended genetic modification present in CD34+ cells of bone marrow over time | 6 months up to 2 years after CTX001 infusion |
| Change in patient-reported outcome (PRO) over time assessed using weekly pain-scale (11-point numerical rating scale [NRS]) | The NRS is a 1-dimensional measure of reporting intensity of pain. The score of NRS ranges from 0 to 10 points, with higher values indicating a higher level of pain. | 3 months up to 2 years after CTX001 infusion |
| Change in PRO over time assessed using EuroQol quality of life scale (EQ-5D-5L) | The EQ-5D-5L Questionnaire consists of the EQ-5D descriptive system and the EQ visual analogue scale (VAS). The EQ-5D comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression, and 5 levels: no problems to extreme problems. The subject marks the most appropriate statement in each dimension, resulting in a 1-digit number for that dimension. The digits can be combined in a 5-digit number describing the subject's health state. The EQ VAS records the subject's self-rated health on a 100-point VAS, endpoints labelled "the best health you can imagine" and "the worst health you can imagine" | 3 months up to 2 years after CTX001 infusion |
| Change in PRO over time assessed using EQ-5D-Youth (EQ-5D-Y) | 3 months up to 2 years after CTX001 infusion |
| Change in PRO over time assessed using functional assessment of cancer therapy-bone marrow transplant (FACT-BMT) questionnaire | The FACT-BMT Questionnaire includes physical, social, family, emotional, and functional well-being, and treatment specific concerns of bone marrow transplantation. Each statement has a 5-point Likert-type response scale ranging from 0=not at all to 4=very much. The subject marks one number per line as it applies to the past 7 days. Questionnaires are then scored; the higher the score, the better the quality of life. | 3 months up to 2 years after CTX001 infusion |
| Change in PRO over time assessed using adult sickle cell quality of life measurement system (ASCQ-Me) | ASCQ-Me comprises measures to assess physical, mental and social health along with information on severity of disease. It includes the following domains: emotional impact, pain impact, pain episodes, sleep impact, social functioning impact, stiffness impact and SCD medical history checklist. ASCQ-Me domains are scored using T-score metric with mean of 50 for reference population and SD of 10. Higher scores indicate healthier status. | 3 months up to 2 years after CTX001 infusion |
| Change in PRO over time assessed using pediatric quality of life inventory (PedsQL) | 3 months up to 2 years after CTX001 infusion |
| Change in PRO over time assessed using PedsQL sickle cell disease module | 3 months up to 2 years after CTX001 infusion |
| Ann & Robert Lurie Children's Hospital of Chicago |
| Chicago |
| Illinois |
| 60611 |
| United States |
| University of Illinois at Chicago Hospitals and Health Systems | Chicago | Illinois | 60612 | United States |
| Columbia University Medical Center (21+ years) | New York | New York | 10032 | United States |
| Columbia University Medical Center (≤21 years) | New York | New York | 10032 | United States |
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| St. Jude Children's Research Hospital | Memphis | Tennessee | 38105 | United States |
| The Children's Hospital at TriStar Centennial Medical Center/ Sarah Cannon Center for Blood Cancers | Nashville | Tennessee | 37203 | United States |
| Methodist Children's Hospital/Texas Transplant Institute | San Antonio | Texas | 78229 | United States |
| Hopital Universitaire des Enfants Reine Fabiola (HUDERF) | Brussels | Belgium |
| The Hospital for Sick Children | Toronto | Canada |
| Hopital Necker Enfants Malades | Paris | France |
| University Hospital Duesseldorf | Düsseldorf | Germany |
| Regensburg University Hospital, Clinic and Polyclinic for Paediatric and Adolescent Medicine, Paediatric Haemotology, Oncology and Stem Cell Transplantation | Regensburg | Germany |
| Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica Ospedale Pediatrico Bambino Gesu - IRCCS | Rome | Italy |
| Imperial College Healthcare NHS Trust, Hammersmith Hospital | London | United Kingdom |
| Royal London and St Bartholomew's Hospital, Pathology and Pharmacy Building | London | United Kingdom |
| 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. |
| 38661449 | Derived | Frangoul H, Locatelli F, Sharma A, Bhatia M, Mapara M, Molinari L, Wall D, Liem RI, Telfer P, Shah AJ, Cavazzana M, Corbacioglu S, Rondelli D, Meisel R, Dedeken L, Lobitz S, de Montalembert M, Steinberg MH, Walters MC, Eckrich MJ, Imren S, Bower L, Simard C, Zhou W, Xuan F, Morrow PK, Hobbs WE, Grupp SA; CLIMB SCD-121 Study Group. Exagamglogene Autotemcel for Severe Sickle Cell Disease. N Engl J Med. 2024 May 9;390(18):1649-1662. doi: 10.1056/NEJMoa2309676. Epub 2024 Apr 24. |
| 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. |
| 34175041 | Derived | Brusson M, Miccio A. Genome editing approaches to beta-hemoglobinopathies. Prog Mol Biol Transl Sci. 2021;182:153-183. doi: 10.1016/bs.pmbts.2021.01.025. Epub 2021 Mar 1. |
| 33283989 | Derived | Frangoul H, Altshuler D, Cappellini MD, Chen YS, Domm J, Eustace BK, Foell J, de la Fuente J, Grupp S, Handgretinger R, Ho TW, Kattamis A, Kernytsky A, Lekstrom-Himes J, Li AM, Locatelli F, Mapara MY, de Montalembert M, Rondelli D, Sharma A, Sheth S, Soni S, Steinberg MH, Wall D, Yen A, Corbacioglu S. CRISPR-Cas9 Gene Editing for Sickle Cell Disease and beta-Thalassemia. N Engl J Med. 2021 Jan 21;384(3):252-260. doi: 10.1056/NEJMoa2031054. Epub 2020 Dec 5. |
| 32873924 | Derived | Modarai SR, Kanda S, Bloh K, Opdenaker LM, Kmiec EB. Precise and error-prone CRISPR-directed gene editing activity in human CD34+ cells varies widely among patient samples. Gene Ther. 2021 Feb;28(1-2):105-113. doi: 10.1038/s41434-020-00192-z. Epub 2020 Sep 1. |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Jul 6, 2026 |
| ID | Term |
|---|---|
| D000755 | Anemia, Sickle Cell |
| D006402 | Hematologic Diseases |
| D006453 | Hemoglobinopathies |
| ID | Term |
|---|---|
| D000745 | Anemia, Hemolytic, Congenital |
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
| D006425 | Hemic and Lymphatic Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
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| ID | Term |
|---|---|
| C000729927 | exagamglogene autotemcel |
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