Clinical trial NCT04963712: Zadaxin and HIV-positive Patients With Immune Reconstitution Disorder
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: HIV-1-infection
Lead sponsor: Shanghai Public Health Clinical Center
Sponsor class: OTHER_GOV
First posted: 2021-07-15
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All participants eligible for study received the same open label drug
Primary purpose: TREATMENT

Brief summary: 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.

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.).

Eligibility criteria: 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.

Primary outcomes:
measure: Change in CD4+T cell counts
timeFrame: Measured on week 24
measure: Change in CD4/CD8 ratio
timeFrame: Measured on week 24
Secondary outcomes:
measure: Change in CD4+T cell count and proportion
timeFrame: Measured on week 0, 4, 8, 12, 24
measure: Change in CD8+T cell count and proportion
timeFrame: Measured on week 0, 4, 8, 12, 24
measure: Change in proportions of T cell subsets
timeFrame: Measured on week 0, 4, 8, 12, 24
measure: Change in proportions of immune exhausted T cells expressed PD-1 and TIM-3
timeFrame: Measured on week 0, 4, 8, 12, 24
measure: Change in PBMC sjTREC
timeFrame: Measured on week 0, 4, 8, 12, 24
measure: Change in HIV-1 RNA
timeFrame: Measured on week 0, 4, 8, 12, 24
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University
state: Shanghai
Study officials:
affiliation: Shanghai Public Health Clinical Center
name: Hongzhou Lu, Ph.D
role: STUDY_DIRECTOR
References: