跳至主要内容
MedPath Trial logoMedPath TrialMedPath Trial Home
临床试验/NCT07680803
NCT07680803招募中2 期

A Single Arm, Open Label, Multicenter, Single-dose, Phase 2b Clinical Study Evaluating Efficacy and Safety of Gene Therapy Using Autologous CD34+ Hematopoietic Stem Cells Transduced With the GLOBE Lentiviral Vector Using an Improved Transduction Protocol in Subjects With Transfusion-dependent Beta-thalassemia

Fondazione Telethon3 个研究点 分布在 1 个国家目标入组 9 人开始时间: 2026年7月6日最近更新:
Share to TwitterShare to FacebookShare to LinkedInShare to Reddit
适应症
干预措施

试验速览

阶段
2 期
状态
招募中
入组人数
9
试验地点
3
主要终点
Proportion of subjects who achieve TI12 in the 2 years from DP administration
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This is a prospective, dual-centre, single dose, Phase IIb, single arm, open label study. The proposed clinical trial involves a single infusion of autologous HSPCs genetically modified with the GLOBE lentiviral vector, using an improved transduction protocol in 9 patients affected by transfusion dependent Beta-Thalassemia.

Four study phases are foreseen:

  1. Screening phase, during which the conditions required by the clinical protocol for patients' inclusion/exclusion will be assessed after the signature of the informed consents/assents. Patients will be recruited from the two participating sites: IRCCS Ospedale San Raffaele (OSR), Department of Pediatric Immunohematology and adult Hematology (OSR Stem Cells Programme) (Milan) and IRCCS Ospedale Pediatrico Bambino Gesù (OPBG), Department of Haematology, Oncology and Gene and Cell Therapy (Rome).
  2. Baseline phase, carried from the end of the screening phase to the day before the start of the conditioning regimen.
  3. Treatment phase, from the first day of conditioning regimen until DP administration.
  4. Follow-up phase: from DP administration until 2 years follow-up.

研究设计

研究类型
Interventional
分配方式
Na
干预模型
Single Group
主要目的
Treatment
盲法
None

入排标准

年龄范围
3 Years 至 35 Years（Child, Adult）
性别
All
接受健康志愿者
否

入选标准

  • •Must be willing to adhere to the protocol as evidenced by written informed consent for adults or parental informed consent and subject assent for adolescents and children.
  • •Male and female adults/adolescents/children diagnosed with transfusion-dependent β-thalassemia (homozygous or compound heterozygous). At least 2 out of the 9 patients must have B0/B0 or B0/B0-like genotype. In case the genetic diagnosis available at screening wasn't performed in a certified laboratory (check under PI's or delegated investigator's responsibility), the genetic diagnosis will be repeated at clinical sites during the screening phase.
  • •Documented history of at least 100 ml/kg/year or 10 U/year of packed red blood cell transfusions in each of the 2 years prior to signing informed consent.
  • •Age ≥ 18 years and ≤ 35 years for Group 1, Age ≥ 3 years and ≤ 35 years for Group
  • •Karnofsky Index or Lansky ≥ 80%.
  • •Adequate cardiac, renal, hepatic and pulmonary functions resulting in eligibility to undergo autologous HSCT as evidenced by:
  • •Left ventricular ejection fraction (LVEF) greater than 45% by echo and normal ECG or presence of abnormalities not significant for cardiac disease. Absence of severe pulmonary hypertension.
  • •Diffusing capacity of the lung for carbon monoxide (DLCO) > 50% and forced expiratory volume in 1 sec (FEV1) and forced expiratory vital capacity (FVC) > 60% predicted (if non cooperative: pulse oximetry > 95 % in room air).
  • •Serum creatinine < 2 x upper limit of normal and estimated GFR > 60 ml/min/1.73m2, calculated using the CKD-EPI formula (Levey 2009) for adults and the modified Schwartz formula (Schwartz 2009) for pediatric patients.
  • •Absent-mild-moderate liver iron overload on T2*MRI (i.e. LIC < 15 mg Fe/gr dry weight assessed at screening. T2*MRI at screening can be avoided if performed less than 6 months before enrolment at treatment centers).
  • •Absent-mild-moderate cardiac iron overload T2*MRI (i.e. > 20 msec assessed at screening. T2*MRI at screening can be avoided if performed less than 6 months before enrolment at treatment centers).
  • •Absence of severe liver fibrosis or cirrhosis on Shear Wave (less than 6 months before enrolment) or of other advanced liver disorder.
  • •For all patients in reproductive age, agreement to use highly effective and adequate method of contraception for at least 12 months following DP administration (including both females of childbearing potential and males with partners of childbearing potential).
  • •Good adherence to transfusion and chelation programme, as indirect evidence of good adherence to treatment and follow-up evaluations for the current trial.
  • •Availability of an adequate and well documented transfusion history (at least previous 24 months) or availability to follow a regular transfusion regimen according to guidelines and provide a detailed transfusion record of the 24 months prior to the DP administration.

排除标准

  • •Use of other investigational agents within 4 weeks prior to study enrolment (within 6 weeks if use of long-acting agents).
  • •Severe, active viral, bacterial or fungal infection at eligibility evaluation.
  • •Current or prior malignant neoplasia (except local skin cancer or cervical intraepithelial neoplasia) or exceptional family history of familial cancer syndromes.
  • •Current or prior immunodeficiency disorder.
  • •History of uncontrolled seizures.
  • •Aspartate transaminase (AST), alanine transaminase (ALT) >3 × the upper limit of normal (ULN), or direct bilirubin value >2.5 × ULN.
  • •Baseline prothrombin time (International Normalized Ratio; INR) >1.5 × ULN.
  • •Other clinical conditions judged non compatible with the procedure and/or the treatment.
  • •Positivity for HIV (serology or RNA), and/or HbsAg and/or HBV DNA and/or HCV RNA (patients who have completed antiviral treatment for HCV may only be enrolled if they have achieved a sustained virologic response, defined as undetectable HCV RNA at least 12 weeks after completion of therapy) and/or evidence of active infection of Treponema Pallidum or Mycoplasma species.
  • •Positive history of significant previous thrombotic events. In case of a positive thrombophilic screening, patient's inclusion will be evaluated according to national guidelines.
  • •Active alcohol or substance abuse within 6 months of the study.
  • •Pregnancy or lactation.
  • •Previous allogeneic hematopoietic stem cell transplantation.
  • •Previous gene therapy treatment (gene addition or gene editing).
  • •For patients until the age of 14 years only: availability of an HLA-matched family donor.
  • •Patients with associated α-thalassemia and >1 alpha deletion, or alpha multiplications.
  • •Any other condition that would not allow the potential subject to complete follow-up examinations during the course of the study and, in the opinion of the investigator, makes the potential subject unsuitable for the study.

研究组 & 干预措施

subjects with transfusion-dependent beta-thalassemia

Experimental

干预措施: FT007 (Genetic)

结局指标

主要结局

Proportion of subjects who achieve TI12 in the 2 years from DP administration

时间窗: from 60 days after the IMP infusion, to 24 months of follow-up

Proportion of Subjects achieving transfusion independence defined as a weighted average Hb ≥ 9.0 gr/dL without any red blood cell transfusion for a continuous period of ≥ 12 months (TI12) at any time during the study after the drug product administration The assessment of TI12 starts 60 days after last RBC transfusion for post-transplant support or BTHAL standard of care.

次要结局

  • Overall survival(12 months and 24 months post IMP infusion)
  • Proportion of Subjects who achieve hematological engraftment ≤ day +60 from DP administration(from Day 11 to Day 60 post IMP infusion)
  • Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) (Safety and tolerability of the administration of FT007)(from Baseline to 24 months post IMP infusion)
  • Proportion of Subjects with abnormal clonal proliferation development due to insertional mutagenesis(6, 12, 18 and 24 months post IMP infusion)
  • Polyclonal and multilineage engraftment evaluated by VCN and ISA(screening, 1, 2, 3, 6, 12, 18 and 24 months after IMP infusion)
  • Proportion of Subjects with immune reconstitution(6 and 12 months post IMP infusion)
  • Characterization of Subjects achieving TI12(24 months after IMP infusion)
  • Characterization of transfusion reduction (TR) among subjects not achieving TI12(12 and 24 months post IMP infusion)
  • Health-related quality of life (HRQoL) - PedsQL(baseline, 12 and 24 months)
  • Health-related quality of life (HRQoL) - FACT BMT(baseline, 12 and 24 months)
  • Health-related quality of life (HRQoL) - EQ-5D-5L(baseline, 12 and 24 months)
  • Health-related quality of life (HRQoL) - EQ-5D-Y(baseline, 12 and 24 months)
  • Proportion of Subjects with engraftment of genetically corrected cells(6, 12, and 24 months after IMP infusion)
  • Levels of biomarkers indicative of ineffective erythropoiesis before and after gene therapy at different time points.(screening and 1, 3, 6, 12, 24 months after IMP infusion)
  • Shear Wave Elastography and Liver Iron Concentration (LIC) over time(screening, 12 and 24 months after IMP infusion)
  • Cardiac T2* value over time(screening, 12 and 24 months after IMP infusion)
  • Ferritin serum levels over time(screening, 3, 6, 12, 18 and 24 months after IMP infusion)
  • Proportion of patients free from any iron-chelating therapy, including regular phlebotomies at month 24(24 months after IMP infusion)
  • Duration of iron-chelating treatment after DP infusion(from Day 1 to 24 months post IMP infusion)

研究者

申办方类型
Other
责任方
Sponsor

研究点 (3)

Loading locations...

相似试验

尚未招募
1 期
Phase I/II Clinical Study to Evaluate the Safety, Tolerability and Efficacy of LY-M003 Injection in Adult Patients With Wilson's Disease
NCT07641140Lingyi Biotech Co., Ltd.18
尚未招募
2 期
Clinical Study on TQH2722 Injection Combined With Background Therapy for Seasonal Allergic Rhinitis
NCT07398859Shanghai Chia Tai Tianqing Pharmaceutical Technology Development Co., Ltd.300
尚未招募
3 期
A study to check the safety and effectiveness of a collagen eye matrix in people with corneal ulcers
CTRI/2026/01/100616ACRO Biomedical Co Ltd150
招募中
1 期
BSG005 in treatment of Patients with Invasive Fungal Infection
CTRI/2024/04/066016Biosergen AS   Official Address-Vestre Rosten 81, Postal code & Name of the country- 7075 Tiller, 1601 Trondheim, Norway15
尚未招募
1 期
WSK-IM02 in Advanced Solid Tumors With Malignant Effusions (Phase I)
NCT07615894WestVac Biopharma Co., Ltd.9