A Proof of Concept Study to Evaluate the Effect of UB-421 in Combination With Chidamide on HIV Viral Reservoir

Official title

A Proof of Concept Study to Evaluate the Safety and Efficacy of UB-421 in Combination With Chidamide for Reduction of HIV Reservoir as Compared to UB-421 Alone in ART Stabilized HIV-1 Patients Who Undergo ART Interruption

Overview

* To assess the impact of UB-421 and chidamide in changing HIV-1 viral reservoir profile among HIV-1 suppressed patients who undergo short-term ART interruption. * To evaluate the safety and tolerability of UB-421 combined with chidamide among HIV-1 suppressed patients who undergo short-term ART interruption.

Interventions

• Biological UB-421
  10mg/kg weekly intravenous infusion to substitute for for antiretroviral therapy
• Other UB-421+chidamide
  10 mg/kg UB-421 weekly intravenous infusion to substitute for antiretroviral therapy, and combined with oral 10 mg chidamide twice a week for 8 weeks. Chidamide taken on the one day and three days after the administration of UB-421.

Primary outcome measures

• HIV-1 Total DNA levels [Time frame: Post-treatment weeks up to 48 weeks]

Secondary outcome measures (4)

• HIV-1 Total DNA levels [Time frame: Post-treatment weeks up to 48 weeks]
• Treatment related TEAE [Time frame: through study completion, an average of 0.5 year]
• Viral suppression [Time frame: Post-treatment weeks up to 48 weeks]
• The number of adverse subjects [Time frame: Post-treatment weeks up to 48 weeks]

Eligibility criteria

Inclusion criteria

Subjects are eligible to be included in the study only if ALL of the following criteria apply:

• HIV-1 sero-positive, with documented HIV-1 infection by official, signed, written history.
• Male with body weight ≥ 50 kg or female with body weight ≥ 45 kg, aged 18 years or older.
• Have been receiving at least (≧) 2 nucleoside/ nucleotide reverse transcriptase inhibitors (NRTI) plus one non-nucleoside reverse transcriptase inhibitor (NNRTI), protease inhibitor (PI, either boosted or un-boosted), integrase strand transfer inhibitor (INSTI) or entry inhibitor (EI) for more than 1 years.
• Have more than 2 different alternative options of optimized ART regimen.
• HIV-1 plasma viral load (VL) level well suppressed below 50 RNA copies/mL for at least (≧) 12 months.
• No breastfeeding or pregnancy for women.
• Both male and female patients and their partners of childbearing potential must agree to use 2 medically accepted methods of contraception (eg, barrier contraceptives \[male condom, female condom, or diaphragm with a spermicidal gel\], hormonal contraceptives \[implants, injectable, combinational oral contraceptives, transdermal patches, or contraceptive rings\], and intrauterine devices) during the course of the study (excluding women who are not of childbearing potential and men who have been sterilized). Females of childbearing potential must have a negative serum pregnancy test.
• Subjects must sign the informed consent before undergoing any study procedures.

Exclusion criteria

Subjects meeting ANY of the following criteria will be excluded from the study:

• Subjects with active systemic infections, except for HIV-1, that the investigator feels the infections may confound evaluation and treatment for HIV-1.
• Any acquired AIDS-defining illness such as non-Hodgkin's lymphoma or Kaposi's sarcoma according to the U.S. Centers for Disease Control and Prevention Classification System for HIV-1 Infection within the past 12 months .
• Any documented CD4+ T cell count < 200 cells/mm3 within the past 12 weeks .
• Any exposure to a monoclonal antibody within the past 12 weeks.
• Any significant diseases (other than HIV-1 infection) or clinically significant findings, that, in the Investigator's opinion, would preclude the subject from well participation or confound the assessment of study objectives.
• Current receiving treatment regimen for Diabetes, hepatitis B, hepatitis C, or latent tuberculosis.
• History of anaphylaxis to any monoclonal antibodies or HDAC inhibitor agents.
• Received blood transfusion or hematopoietic growth factor treatment, any vaccine, or a compound with HDAC inhibitor activity (such as valproic acid) recently.
• Use of immunomodulators, HIV vaccine, or systemic chemotherapy within 180 days prior to V1.
• More than one change of ART regimen because of the inability to achieve or maintain suppression of viral replication to an HIV-1 RNA level < 200 copies/mL within the past 12 months
• Receipt of any other investigational study agent(s) within 90 days.
• Experienced urticaria in recent 6 months or ongoing or unresolved skin problems with rash-like symptoms .

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT04985890 · UBP-A230-HIV

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗