iHSCs With the Gene Correction of HBB Intervent Subjests With β-thalassemia Mutations

A Safety and Efficacy Study of a Single Center, Open-label, Single Arm About the Gene Correction of HBB in Patient-specific iHSCs Using CRISPR/Cas9 That Intervent Subjests With β-thalassemia Mutations

This is a single centre、single arm、open-label study，to investigate the safety and efficacy of the gene correction of HBB in patient-specific iHSCs using CRISPR/Cas9.

Study Overview

• Status: Unknown
• Conditions: Thalassemia
• Intervention / Treatment: Biological: iHSCs treatment group

Detailed Description

The purpose of this study is to evaluate the efficacy and safety of transplantation iHSCs intervent subjests with β-thalassemia mutations.

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Early Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 60 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects ≥ 2 and ≤ 60 years of age
2. Subjects was confirmed the transfusion-dependent β-thalassemia

3. Adequate organ function, as defined by:

   Serum creatinine ≤ 1.5 mg/dl ； Serum ALT/AST）≤2.5×ULN；ALB≥25g/L； Serum total bilirubin < 1.5x ULN Left ventricular ejection fraction≥50%

4. Chest X-ray and ecg test results were normal, no serious cardiopulmonary diseases
5. Subjects survival was expected≥6 months
6. Adult patients were willing to use reliable contraceptives (such as condoms) and not to donate sperm throughout the study period and within three months of discharge
7. Subjects and the guardians able to undergo post-physical therapy/rehabilitation

Exclusion Criteria:

1. Subjects allergic to macromolecular biological agents such as antibodies or cytokines
2. Subjects receipt of any investigational clinical trials within 3 months.
3. Subjects previous treatment with any hematopoietic stem cell transplantation or other organ transplantation
4. Uncontrolled bleeding symptoms

5. Severe cardiovascular disease is known, including any of the following:

   Myocardial infarction or thrombosis has occurred in the past six months Subjects with unstable angina pectoris Subjects with Class III/IV cardiovascular disability according to the New York Heart Association Classification

6. Subjects have one kinds of tumors within 5 years
7. Active hepatitis B (HBV DNA>1000copy/mL), hepatitis C or HIV infection.
8. Subjects have an infectious diseases that cannot be controlled within 4 weeks
9. subjects have severe central nervous system disease or epilepsy
10. Subjects are Suffering from mental illness; Patients with alcohol dependence, drug abuse, drug addiction, and medical, psychological or social conditions that may interfere with research or have an impact on the evaluation of research results
11. Women in pregnancy (positive urine/blood pregnancy test) or lactation
12. Subjects who have other conditions that were not appropriate for the group determined by the researchers.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: iHSCs treatment group	Biological: iHSCs treatment group; iHSCs intravenous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of treatment related adverse events as assessed by CTCAE v4.0	Defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical events) that are possibly, likely, or definitely related to study treatment	1 year

Collaborators and Investigators

• Sponsor: Allife Medical Science and Technology Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2019
• Primary Completion (Anticipated): January 1, 2020
• Study Completion (Anticipated): January 1, 2021

Study Registration Dates

• First Submitted: October 31, 2018
• First Submitted That Met QC Criteria: October 31, 2018
• First Posted (Actual): November 2, 2018

Study Record Updates

• Last Update Posted (Actual): November 5, 2018
• Last Update Submitted That Met QC Criteria: November 1, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Thalassemia; beta-Thalassemia
• Other Study ID Numbers: HBB HSC-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No