Zadaxin and HIV-positive Patients With Immune Reconstitution Disorder

A Prospective Single-arm Cohort Study Evaluating the Safety and Efficacy of Thymalfasin (Zadaxin®) in the Treatment of HIV-positive Patients With Immune Reconstitution Disorders

The purpose of this study is to evaluate the safety and efficacy of Zadaxin® in the treatment of HIV-positive patients with immune reconstitution disorders. Researchers previously used Zadaxin® (Thymosin α-1, Tα1) as an immune adjuvant for people infected with HIV-1 and found that Tα1 and Interferon-α (IFN-α) have a synergistic effect in immune enhancement. In addition, studies have found that the triple combination of Tα1, IFN-α and Zidovudine has better tolerability, safety and efficacy. After treatment, patients have lower HIV RNA and more stable high CD4+ T cell counts. In addition, extensive studies on the administration of Tα1 in thymectomized mice have demonstrated its ability to promote immune reconstitution. The researchers hypothesized that Zadaxin® has a better therapeutic effect on HIV-positive patients with immune reconstitution disorders, can increase the CD4+T cell count, reduce the viral load, and has better safety.

Study Overview

• Status: Completed
• Conditions: HIV-1-infection
• Intervention / Treatment: Drug: Zadaxin

Detailed Description

All patients received Zadaxin (1.6 mg subcutaneous injection, once a day) in the first 2 weeks, and changed frequency (1.6 mg subcutaneous injection, twice a week) in the successive 22 weeks. It is still recommended to continue treatment until the end of the study. All subjects were given HAART treatment throughout. In 4th week, 8th week, 12th week and 24th week, perform 4 follow-up and record the changes in CD4+ T cell count and proportion, CD8+ T cell count and proportion, proportions of T cell subsets, PBMC sjTREC, proportions of exhauseted T cell expressed PD-1 and Tim-3, and HIV viral load. During the process, safety assessment is performed, including adverse events, electrocardiogram and a series of laboratory tests (blood routine, liver and kidney function, etc.).

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18-65 years old;
• HIV serology is positive;
• Volunteer to participate;
• CD4+T cell count >100 and <350 cells/mm3;
• People who have received HAART treatment and the viral load is undetected for at least 2 years, but have immune reconstitution disorder;
• Without active opportunistic infection;

Exclusion Criteria:

• History of allergy or contraindications to Zadaxin;
• Skin basal cell carcinoma, cervical carcinoma in situ or other concurrent tumors other than Kaposi's sarcoma;
• The expected survival time is less than 1 year;
• Women of childbearing age have a positive pregnancy test;
• Major heart disease or central nervous system disease or other nervous system abnormalities;
• ACTG-AIDS dementia syndrome staging score> 0.5;
• Organ transplantation;
• Received chemotherapy and radiotherapy for malignant tumors within 6 months;
• Known immunomodulators (such as systemic steroids, interferons, interleukins) or other immunotherapy within 30 days before the start of the study;
• Blood transfusion within 30 days before the start of the study;
• Have a history of iritis, endophthalmitis, scleritis or retinitis;
• Within 30 days before the screening assessment, accept any experimental treatment for HIV-positive patients with or without symptoms of infection;
• Drug abuse;
• The doctor's decision is that participation in the trial is not in the patient's best interests, or any situation that does not allow safe compliance with the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zadaxin-HIV(n=20); Study participants will be given Zadaxin (1.6 mg subcutaneous injection, once a day) in the first 2 weeks, and changed frequency (1.6 mg subcutaneous injection, twice a week) in the successive 22 weeks.	Drug: Zadaxin; 1.6 mg subcutaneous injection, once a day in the first 2 weeks, and 1.6 mg subcutaneous injection, twice a week in the successive 22 weeks.; Other Names: Thymosin α1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in CD4+T cell counts	Peripheral blood	Measured on week 24
Change in CD4/CD8 ratio	Peripheral blood	Measured on week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in CD4+T cell count and proportion	Peripheral blood	Measured on week 0, 4, 8, 12, 24
Change in CD8+T cell count and proportion	Peripheral blood	Measured on week 0, 4, 8, 12, 24
Change in proportions of T cell subsets	Peripheral blood mononuclear cell	Measured on week 0, 4, 8, 12, 24
Change in proportions of immune exhausted T cells expressed PD-1 and TIM-3	Peripheral blood mononuclear cell	Measured on week 0, 4, 8, 12, 24
Change in PBMC sjTREC	Peripheral blood mononuclear cell	Measured on week 0, 4, 8, 12, 24
Change in HIV-1 RNA	Plasma	Measured on week 0, 4, 8, 12, 24

Collaborators and Investigators

• Sponsor: Shanghai Public Health Clinical Center
• Investigators: Study Director: Hongzhou Lu, Ph.D, Shanghai Public Health Clinical Center

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2021
• Primary Completion (Actual): July 22, 2022
• Study Completion (Actual): August 11, 2022

Study Registration Dates

• First Submitted: July 7, 2021
• First Submitted That Met QC Criteria: July 13, 2021
• First Posted (Actual): July 15, 2021

Study Record Updates

• Last Update Posted (Actual): July 18, 2023
• Last Update Submitted That Met QC Criteria: July 15, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Urogenital Diseases; Genital Diseases; HIV Seropositivity; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; Thymalfasin
• Other Study ID Numbers: Zadaxin-HIV

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No