A Trial of Anti-CD4 Antibody UB-421 in Combination With Optimized Background Antiretroviral Therapy in Patients With Multi-Drug Resistant HIV-1 Infection

Phase 2

Recruiting

• Conditions: HIV-1 Infection; Multi-Drug Resistant Hiv-1 Infection
• Interventions: Biological: UB-421

• Registration Number: NCT05582694
• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary

Background:

People with HIV usually take a combination of 2 or more anti-HIV drugs daily to help manage their infection. Sometimes, however, HIV becomes resistant to these drugs, and the infection cannot be treated. Untreated HIV infection can make people more vulnerable to other infections as well as some cancers. Better treatments are needed for people with drug-resistant HIV.

Objective:

To see if a study drug (UB-421) is effective in people with drug-resistant HIV.

Eligibility:

People aged 18 years and older with HIV that is resistant to anti-HIV drugs.

Design:

Participants will be in the study for 35 weeks.

Participants will have separate screening and baseline visits within 2 months of each other. They will have a physical exam with blood and urine tests both times. On the second visit, they will undergo apheresis: Blood will be drawn from a needle in one arm. The blood will pass through a machine that separates out the white blood cells. The remaining blood will be given back through a second needle in the other arm.

Participants will begin receiving the study drug 1 week after their baseline visit. UB-421 is given through a tube attached to a needle placed in a vein in the arm. They will return for UB-421 treatments every week for 26 weeks. Each visit will take 3 to 6 hours.

Participants will have 2 follow-up visits 4 and 8 weeks after their last treatment with UB-421. Apheresis will be repeated at 1 of these visits.

Detailed Description

Study Description:

This is a Phase 2 single arm study to evaluate the efficacy and safety of UB-421 in conjunction with an existing failing antiretroviral therapy (ART) for 2 weeks followed by optimized background therapy (OBT) in conjunction with UB-421 for 24 weeks.

Objectives:

Primary Objectives:

To assess the antiviral activity of UB-421 in reducing human immunodeficiency virus type 1 (HIV-1) plasma viremia during the 2-week functional monotherapy treatment period.

Secondary Objectives:

* Evaluate the antiviral activity of UB-421 during the 24-week maintenance treatment period.

* Evaluate changes from baseline in CD4+ and CD8+ T cell counts during the UB-421 treatment period.

* Evaluate the pharmacokinetic parameters of UB-421.

* Evaluate the immunogenicity of UB-421 by the presence of anti-UB-421 antibodies.

Endpoints:

Primary Efficacy Endpoint:

-Number of participants with \>=0.5 log10 reduction in HIV-1 plasma viremia from baseline (Day 7) to Day 21.

Primary Safety Endpoint:

-The number of grade 2 or higher adverse events (AEs), including serious adverse events (SAEs), which are possibly, probably or definitely related to UB-421.

Secondary Endpoints:

* Number of participants achieving \>=1 log10 reduction in HIV-1 plasma viremia from baseline (Day 7) to Day 21.

* Number of participants achieving HIV-1 plasma viremia \<40 copies/mL at the end of treatment (EOT-Study week 27).

* Number of participants achieving HIV-1 ribonucleic acid (RNA) \<200 copies/mL at the EOT.

* Mean change in CD4+ and CD8+ T cell counts from baseline (Day 7) to EOT for all evaluable subjects.

* Measured levels of anti-UB-421 antibodies in participant blood samples.

* Measured levels of serum UB-421 concentration (pharmacokinetic parameters) in participant blood samples.

Study Timeline

• Study First Submitted: 2022-10-14
• Study First Submitted QC: 2022-10-14
• Study First Posted: 2022-10-17
• Study Start: 2023-07-26
• Status Verified: 2024-10-01
• Last Update Submitted: 2024-10-02
• Last Update Posted: 2024-10-03
• Primary Completion: 2025-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

Not provided

Read More

Exclusion Criteria

Not provided

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1	UB-421	10 adults (\>18 years of age) with human immunodeficiency virus (HIV) who demonstrate evidence of HIV-1 replication despite ongoing ART with documented genotypic and/or phenotypic resistance to multiple classes of HIV drugs (3 classes or more)

Primary Outcome Measures

Name	Time	Method
Number of participants with =0.5 log10 reduction in HIV-1 plasma viremia	baseline (Day 7) to Day 21	Number of participants with =0.5 log10 reduction in HIV-1 plasma viremia from baseline (Day 7) to Day 21.
The number of grade 2 or higher adverse events (AEs)	treatment phase	The number of occurrence of grade 2 or higher adverse events (AEs), including serious adverse events (SAEs), which are probably or definitely related to UB-421.

Secondary Outcome Measures

Name	Time	Method
Number of participants achieving HIV-1 RNA <200 copies/mL	Baseline (Day 7) through EOT	Number of participants achieving HIV-1 RNA \<200 copies/mL at the EOT.
Measured levels of anti-UB-421 antibodies	Baseline (Day 7) through EOT	Measured levels of anti-UB-421 antibodies in participant blood samples.
Number of participants achieving HIV-1 plasma viremia <40 copies/mL	Baseline (Day 7) through EOT	Number of participants achieving HIV-1 plasma viremia \<40 copies/mL at the end of treatment (EOT-Study week 27).
Measured levels of serum UB-421 concentration	Baseline (Day 7) through EOT	Measured levels of serum UB-421 concentration (pharmacokinetic parameters) in participant blood samples.
Mean change in CD4+ and CD8+ T cell counts	Baseline (Day 7) through EOT	Mean change in CD4+ and CD8+ T cell counts from baseline (Day 7) to EOT for all evaluable subjects.

Trial Locations

Locations (1)

National Institutes of Health Clinical Center; 🇺🇸 Bethesda, Maryland, United States