Safety and Efficacy Study of NGGT003 in Hemophilia A Patients

NCT06238908 | Recruiting Early Phase 1

• 1 other identifier: IIT2023043
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This is an early phase 1, open-label, single-center, dose-escalation pilot trial to evaluate the safety and efficacy of an intravenous infusion of NGGT003 in hemophilia A patients. NGGT003 uses adeno-associated virus (AAV) as a vector, carrying a liver specific promoter and codon optimized human FVIII gene B domain deletion mutant (hFVIII BDD), and expresses human FVIII protein in the liver through intravenous injection.

Conditions

Hemophilia A

Outcome Measures

Primary Outcomes (2)

• Adverse events (AEs) and serious adverse events (SAEs)

  Incidence of AE and SAE, as assessed by physical examinations, clinical laboratory parameters and adverse event reporting

  52 weeks

• Changes in annualized bleeding rate (ABR)

  Changes in annualized bleeding rate (ABR) from baseline to 52 weeks.

  52 weeks

Secondary Outcomes (4)

• FVIII activity levels

  52 weeks

• FVIII protein product infusions

  52 weeks

• Target joints

  52 weeks

• HA-QOL scores

  52 weeks

Study Arms (1)

Experimental

EXPERIMENTAL

3 doses of NGGT003 will be administered according to the principle of dose escalation

Drug: NGGT003

Interventions

NGGT003 DRUG

Single intravenous infusion of NGGT003 at low dose (4e11vg/kg), medium dose (1e12vg/kg) and high dose (2.5e12vg/kg)

Experimental

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily sign the informed consent form;
• Male, age ≥18 years old;
• Diagnosed with hemophilia A according to the "Guidelines for Diagnosis and Treatment of Hemophilia A (2022 Edition)", and the endogenous FVIII activity level was \<1 IU/dL (\<1%);
• The exposure days (EDs) of treatment with any recombinant or plasma-derived FVIII product were ≥150 days;
• Anti-AAV neutralizing antibody titer ≤1:5, binding antibody titer ≤1:100;
• Bleeding events and/or FVIII product injections have occurred within 12 weeks before screening;
• No history of allergy to FVIII products;
• FVIII inhibitor titer﹤0.6BU/mL;
• Commitment to use other drugs during the study requires the consent of the investigator;
• Willing and able to comply with study procedures and requirements;
• Willing to use effective contraceptive methods within 52 weeks after administration.

You may not qualify if:

• Positive for hepatitis B surface antigen, hepatitis C, human immunodeficiency virus (HIV)，syphilis test;
• Clinically significant abnormalities in liver function test: alanine aminotransferase (ALT) \>1.5 × upper limit of normal (ULN) and/or aspartate aminotransferase (AST) \>1.5× ULN;TBil）\>1.5×ULN；Serum creatinine (Scr) \>1.5×ULN; hemoglobin \<110g/L, platelets \<10e9/L;
• History of being positive for FVIII inhibitors;
• Have other bleeding factors except hemophilia;
• Plan major surgery within 52 weeks;
• Have contraindications to glucocorticoid, including but not limited to allergy to glucocorticoids, epilepsy, new unhealed fractures, in trauma repair period, uncontrolled infection, severe osteoporosis, etc, which assessed and determined by the investigators;
• History of allergy to human albumin;
• Have serious diseases or active infections in cardiovascular, respiratory, digestive tract, endocrine, renal, blood, nervous, mental and other systems before screening;
• With hepatitis, cirrhosis, liver cancer or other major liver diseases;
• History of malignant tumors;
• Abnormal and clinical significant vital signs, physical examination, laboratory examination or other related examination results during the screen, which are not suitable for trial according to the investigator;
• Previous gene therapy treatment;
• Participation in any other clinical trial before the screening and have taken medication within four weeks or five half-lives of the study drug;
• Any other condition that may not be appropriate for the study in the opinion of the investigator.

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

Study Sites (1)

Institute of Hematology & Blood Diseases Hospital

Tianjin, Tianjin Municipality, 300020, China

RECRUITING

MeSH Terms

Conditions

Hemophilia A

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Lei Zhang, MD

  Institute of Hematology & Blood Diseases Hospital, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wei Liu, MD

CONTACT

+862223909240; liuwei1@ihcams.ac.cn

Lei Zhang, MD

CONTACT

+862223909240; zhanglei1@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2024
• First Posted: February 2, 2024
• Study Start: January 17, 2024
• Primary Completion: January 31, 2026
• Study Completion (Estimated): January 31, 2030
• Last Updated: February 21, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)