An Open Label, Single Arm, Phase I/II Clinical Study of Autologous CD4+ T-Cells Edited Ex-Vivo at the CD40LG Locus by CRISPR/Cas9 and IDLV-based vector in Patients with X-linked Hyper IgM Syndrome Type 1 (HIGM1)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- Proportion of patients experiencing dose-limiting toxicities (DLTs) after each drug product (DP) dose
研究概览
简要总结
To evaluate safety of the treatment with FT018 in patients with HIGM1
入排标准
- 年龄范围
- 0 years 至 65+ years（65+ Years, 18-64 Years, 0-17 Years）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Signature of informed consent
- •Male subject
- •≥ 1year of age
- •Lansky/Karnofsky ≥ 80%
- •Genetic diagnosis of HIGM1
- •Absent/reduced expression or functionality of CD40L on CD4+ T-cells upon in vitro stimulation with PMA/ionomycin
- •Requirement of chronic IgRT
- •Good adherence to IgRT
排除标准
- •CD40LG mutation upstream of the vector insertion site in CD40LG intron 1 or any other mutation not amenable to correction with gene editing
- •Contraindication to vaccination included in the protocol or other medications/procedures foreseen in the protocol
- •Exposure to any prior cell or gene therapies
- •Documented HIV RNA, HCV RNA or HBV DNA positivity, presence of total syphilis antibodies and compliance to Tissue Directive (manufacturing issue)
- •End-organ dysfunction or other severe disease or clinical condition which, in the judgment of the Investigator, would make the subject inappropriate for entry into this study
- •Has previously undergone allogeneic hematopoietic stem cell transplantation and has evidence of residual cells of donor origin.
- •Patient enrolled in other clinical trials
- •Patient unable to donate a sufficient number of lymphocytes for drug product manufacturing
- •Systemic corticosteroid therapy or other immunosuppressive drugs that may interfere With apheresis or the DP
研究组 & 干预措施
TICOVAC 0,5 ml Sospensione iniettabile in una siringa preriempita Vaccino (virus intero, inattivato) contro l’encefalite da zecca, TICOVAC 0,25 ml per uso pediatrico Sospensione iniettabile in una siringa preriempita Vaccino (virus intero, inattivato) contro l'encefalite da zecca
干预措施: TICOVAC 0,5 ml Sospensione iniettabile in una siringa preriempita Vaccino (virus intero, inattivato) contro l’encefalite da zecca (Drug)
TICOVAC 0,5 ml Sospensione iniettabile in una siringa preriempita Vaccino (virus intero, inattivato) contro l’encefalite da zecca, TICOVAC 0,25 ml per uso pediatrico Sospensione iniettabile in una siringa preriempita Vaccino (virus intero, inattivato) contro l'encefalite da zecca
干预措施: TICOVAC 0,25 ml per uso pediatrico Sospensione iniettabile in una siringa preriempita Vaccino (virus intero, inattivato) contro l'encefalite da zecca (Drug)
AUTOLOGOUS PERIPHERAL BLOOD-DERIVED CD4+ T-CELLS CRISPR-EDITED AT THE CD40LG LOCUS
干预措施: AUTOLOGOUS PERIPHERAL BLOOD-DERIVED CD4+ T-CELLS CRISPR-EDITED AT THE CD40LG LOCUS (Drug)
Rabipur Polvere e solvente per soluzione iniettabile in siringa preriempita. Vaccino rabico (inattivato).
干预措施: Rabipur Polvere e solvente per soluzione iniettabile in siringa preriempita. Vaccino rabico (inattivato). (Drug)
Infanrix hexa, Powder and suspension for suspension for injection. Diphtheria (D), tetanus (T), pertussis (acellular, component) (Pa), hepatitis B (rDNA) (HBV), poliomyelitis (inactivated) (IPV) and Haemophilus influenzae type b (Hib) conjugate vaccine (adsorbed).
干预措施: Infanrix hexa, Powder and suspension for suspension for injection. Diphtheria (D), tetanus (T), pertussis (acellular, component) (Pa), hepatitis B (rDNA) (HBV), poliomyelitis (inactivated) (IPV) and Haemophilus influenzae type b (Hib) conjugate vaccine (adsorbed). (Drug)
结局指标
主要结局
Proportion of patients experiencing dose-limiting toxicities (DLTs) after each drug product (DP) dose
Proportion of patients experiencing dose-limiting toxicities (DLTs) after each drug product (DP) dose
次要结局
- Occurrence of: - Adverse events (AEs) - Serious adverse events (SAEs)Adverse events of special interest (AESIs) - DP-related AEs - Immune reconstitution inflammatory Syndrome (IRIS) (number, grading and proportion of patients experiencing IRIS) evaluated at 28 days after each dose, 6 months, 1 year and 2 years after treatment
- Proportion of patients receiving the boost DP dose
- Overall survival at 6 months, 1 year and 2 years after treatment
- Incidence rate, duration and proportion of days with moderate-severe infection in the 2 years preceding and in the 2 years after treatment, evaluated in consecutive 6- month time windows (6 months, 1 year, 1.5 years and 2 years)
研究者
Regulatory Affairs
Scientific
Fondazione Telethon Ets