A Long-term Follow-up Study in Participants Who Received CTX001

Официальное название

A Long-term Follow-up Study of Subjects With β-thalassemia or Sickle Cell Disease Treated With Autologous CRISPR-Cas9 Modified Hematopoietic Stem Cells (CTX001)

Обзор

This is a multi-site, open- label rollover study to evaluate the long-term safety and efficacy of CTX001 in pediatric and adult participants who received CTX001 in parent studies 111 (NCT03655678) 141 (NCT05356195) or 161 (NCT05477563) (transfusion-dependent β-thalassemia \[TDT\] studies) or Study 121 (NCT03745287) or 151 (NCT05329649) or 161(NCT05477563) (severe sickle cell disease \[SCD\] studies).

Вмешательства

• Биопрепарат CTX001
  CTX001 infusion.

Первичные конечные точки

• New malignancies [Срок оценки: Signing of informed consent up to 15 years post CTX001 infusion]
• New or worsening hematologic disorders [Срок оценки: Signing of informed consent up to 15 years post CTX001 infusion]
• All-cause mortality [Срок оценки: Signing of informed consent up to 15 years post CTX001 infusion]
• Serious adverse events (SAEs) [Срок оценки: Signing of informed consent up to 15 years post CTX001 infusion]
• CTX001-related adverse events (AEs) [Срок оценки: Signing of informed consent up to 15 years post CTX001 infusion]

Вторичные конечные точки (12)

• TDT and SCD: Total Hemoglobin (Hb) concentration over time [Срок оценки: Up to 15 years post CTX001 infusion]
• TDT and SCD: Fetal Hemoglobin (HbF) concentration over time [Срок оценки: Up to 15 years post CTX001 infusion]
• TDT and SCD: Proportion of alleles with intended genetic modification present in peripheral blood over time [Срок оценки: Up to 15 years post CTX001 infusion]
• TDT and SCD: Proportion of alleles with intended genetic modification present in CD34+ cells of the bone marrow over time [Срок оценки: Up to 15 years post CTX001 infusion]
• TDT and SCD: Change in patient-reported outcome (PRO) over time in participants ≥18 years of age assessed using EuroQol quality of life scale (EQ-5D-5L) for participants from study 111 and 121 only [Срок оценки: Up to 5 years post CTX001 infusion]
• TDT and SCD: Change in PROs over time in participants ≥18 years of age assessed using functional assessment of cancer therapy-bone marrow transplant (FACT-BMT) questionnaire for participants from study 111, 121 and 161 only [Срок оценки: Up to 5 years post CTX001 infusion]
• TDT and SCD: Change in PROs over time in participants <18 years assessed using EQ-5D-Youth (EQ-5D-Y) from study 111,121,141 and 151 only [Срок оценки: Up to 5 years post CTX001 infusion]
• TDT and SCD: Change in PROs over time in participants <18 years assessed using pediatric quality of life inventory (PedsQL) Core [Срок оценки: Up to 5 years post CTX001 infusion]
• TDT: Proportion of participants achieving transfusion independence for at least 12 consecutive months (TI12) [Срок оценки: From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion]
• TDT: Proportion of participants achieving transfusion independence for at least 6 consecutive months (TI6) [Срок оценки: From 60 days after last RBC transfusion up to 15 years post-CTX001 infusion]
• TDT: Proportion of participants achieving at least 95%, 90%, 85%, 75%, 50% reduction from baseline in annualized volume of RBC transfusions starting after month 10 after CTX001 infusion for participants who have not achieved TI12 [Срок оценки: From Month 10 up to 15 years post-CTX001 infusion]
• TDT: Duration of transfusion free in participants who have achieved TI12 [Срок оценки: From 60 days after last RBC transfusion up to 15 years post CTX001 infusion]

Критерии участия

Критерии включения

• Participants (or his or her legally appointed and authorized representative or guardian) must sign and date informed consent form (ICF) and, where applicable, an assent form
• Participants must have received CTX001 infusion in a parent study

Критерии исключения

• There are no exclusion criteria

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Другое

Центры проведения

США · 9 центров

• Lucile Packard Children's Hospital — Palo Alto
• Ann & Robert H. Lurie Children's Hospital of Chicago - Hematology — Chicago
• Herbert Irving Pavilion - Hematology — New York
• New York Presbyterian Hospital - Morgan Stanley Children's Hospital — New York
• Levine Children's Hospital - Hematology — Charlotte
• The Children's Hospital of Philadelphia - Hematology — Philadelphia
• St. Jude Children's Research Hospital — Memphis
• TriStar Medical Group Children's Specialists - Pediatric Oncology — Nashville
• … и ещё 1 центр

Канада · 3 центра

• Hospital for Sick Children - Hematology — Toronto
• Toronto General Hospital - Hematology — Toronto
• St. Paul's Hospital - Hematology — Vancouver

Германия · 3 центра

• University Hospital Duesseldorf - Department of Pediatric Oncology, Hematology and Clinica — Düsseldorf
• Center for Pediatric Clinical Studies (CPCS) — Klinik Für Kinder- Und Jugendmedizin
• Regensburg University Hospital, Clinic and Polyclinic for Paediatric and Adolescent Medici — Regensburg

Великобритания · 3 центра

• Great Ormond Street Hospital for Children — London
• Hammersmith Hospital - Haematology Dept — London
• University College London Hospital NHS Foundation - Main — London

Бельгия · 1 центр

• Hopital Universitaire des Enfants Reine Fabiola (HUDERF) - Hematology — Brussels

Италия · 1 центр

• IRCSS Ospedale Pediatrico Bambino Gesu - Dipartimento di Onco-Ematologia e Terapia Cellula — Rome

Публикации

• Sheth S, Corbacioglu S, de la Fuente J, Algeri M, Rupprecht J, Kuo KHM, Shah AJ, Lang P, Merkeley H, Carpenter B, Mapara MY, Liem RI, Grupp S, Chopra Y, Li AM, Kwiatkowski JL, Kirby-Allen M, Cappellini MD, Kattamis A, Zairis S, Liu T, Hobbs W, Frangoul H, Locatelli F, Meisel R; CLIMB THAL-111 and CLIMB-131 Study Groups. Correction of Ineffective Erythropoiesis and Normalization of Iron Homeostasis PMID 42252696
• Fuente J, Frangoul H, Lang P, Wall D, Meisel R, Corbacioglu S, Li AM, Shah AJ, Carpenter B, Kwiatkowski JL, Mapara MY, Liem RI, Rupprecht J, Kuo KHM, Merkeley H, Algeri M, Smith W, Kohli P, Li N, Rubin J, Zhang S, Hobbs W, Locatelli F. Improvements in health-related quality of life in patients with transfusion-dependent beta-thalassemia after exagamglogene autotemcel. Blood Adv. 2025 Dec 23;9(24): PMID 40862696
• 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. PMID 40857358

Идентификаторы

NCT: NCT04208529 · VX18-CTX001-131 · 2024-512654-19-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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