Safety and Preliminary Efficacy of CTX112 in Adult Participants With Relapsed/Refractory Hematologic Autoimmune Disease

Официальное название

A Phase 1/2 Dose Evaluation Trial of the Safety and Preliminary Efficacy of Anti CD19 Allogeneic CRISPR-Cas9-Engineered T Cells (CTX112) in Adult Participants With Relapsed/Refractory Hematologic Autoimmune Disease

Обзор

This is a single-arm, open-label, multicenter, ascending dose Phase 1/2 trial evaluating the safety and preliminary efficacy of CTX112 or Zugocabtagene geleucel (zugo-cel) in adult participants with relapsed/refractory primary Immune Thrombocytopenia (ITP) and relapsed/refractory primary Warm Autoimmune Hemolytic Anemia (wAIHA).

Подробное описание

This trial will assess the safety and preliminary efficacy of CTX112 or Zugocabtagene geleucel (zugo-cel) in adults with relapsed or refractory hematologic autoimmune diseases (AID), including primary ITP and primary wAIHA. In these B-cell-mediated conditions, autoantibodies target platelets (ITP) or red blood cells (wAIHA), causing severe thrombocytopenia or anemia. Although several treatments exist, some patients relapse or remain refractory, resulting in significant morbidity, mortality, and reduced quality of life. This underscores the need for new therapeutic options.

B-cell-directed therapies are central to current management, and emerging data show promising activity of anti-CD19 CAR T cell therapies in AID. CTX112 (zugo-cel) is an allogeneic, CD19-targeted CAR T cell product derived from healthy donors and genetically modified ex vivo using CRISPR-Cas9. Similar to autologous CD19 CAR T therapies, CTX112 (zugo-cel) may induce clinical responses after a single treatment and offers the advantages of off-the-shelf availability.

Up to 60 participants may be enrolled. Study duration will be up to 5 years.

Вмешательства

• Биопрепарат CTX112
  CTX112 (zugo-cel): CD19-directed T-cell immunotherapy comprised of allogeneic T cells genetically modified ex vivo using CRISPR-Cas9 gene editing components

Первичные конечные точки

• To evaluate the safety of CTX112 in adult participants with refractory hematologic autoimmune diseases, including ITP or wAIHA. [Срок оценки: From CTX112 infusion up to 28 days post infusion.]

Вторичные конечные точки (3)

• To assess the pharmacodynamics response to CTX112 in adult participants with ITP or wAIHA. [Срок оценки: From CTX112 infusion up to 60 months post-infusion]
• To assess the pharmacokinetics (PK) of CTX112 in adult participants with ITP or wAIHA. [Срок оценки: From CTX112 infusion up to 60 months post-infusion.]
• To assess the preliminary efficacy of CTX112 in adult participants with ITP or wAIHA. [Срок оценки: From CTX112 infusion up to 60 months post-infusion]

Критерии участия

Критерии включения

• Age ≥18 years.
• Participants must voluntarily sign a written informed consent and be willing and able to comply with all trial requirements.
• Adequate hematologic, renal, liver, cardiac and pulmonary function.
• Participants must agree to use acceptable methods of contraception.
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests, contraceptive guidelines, and other trial procedures.
• Diagnosis of relapsed/refractory primary Immune Thrombocytopenic Purpura (ITP) or Warm Autoimmune Hemolytic Anemia (WAIHA)

Критерии исключения

• Prior treatment with anti-CD19 therapy or any gene therapy or genetically modified cell therapy.
• Prior solid organ (e.g., heart, liver, kidney, lung) transplant or hematopoietic cell transplant.
• Severe active or history of central nervous (CNS) involvement.
• Presence of other active autoimmune disease or other conditions that are likely to pose increased safety risks and/or confound disease assessments, or pose significant risk to those receiving CAR T cell therapy.
• History of primary or secondary immunodeficiency.
• Presence or history of certain bacterial, viral or fungal infection
• Malignancy in the last 5 years (with the exception of cancers deemed to be low likelihood for recurrence).
• Diagnosis of a genetic disorder associated with bone marrow failure or myelodysplastic syndrome.
• History or current diagnosis that requires uninterrupted, ongoing anticoagulation.
• Pregnant or lactating.
• Presence or history of disease requiring treatment that is not compatible with the study protocol; presence or history of other conditions that are not compatible with the study protocol.

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

Лечение

Центры проведения

Германия · 4 центра

• Universitaetsklinikum Koeln — Cologne
• Medizinische Hochschule Hannover — Hannover
• Medizinische Hochschule Hannover (MHH) — Hanover
• UCT University Medical Center Mainz — Mainz

Испания · 4 центра

• Hospital Universitario Reina Sofia — Córdoba
• Gregorio Marañón General University Hospital — Madrid
• Hospital Universitario La Paz — Madrid
• Hospital Universitario Virgen del Rocio — Seville

США · 2 центра

• Mayo Clinic in Rochester — Rochester
• University of Nebraska Medical Center — Omaha

Идентификаторы

NCT: NCT07549698 · CRSP-AID-501

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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