Albuvirtide in Combination With 3BNC117 in Virologically Suppressed Subjects With HIV-1 Infection

NCT ID: NCT04819347

Last Updated: 2021-03-26

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-05-01
• Study Completion Date: 2022-12-01

Brief Summary

This is a phase 2 study to evaluate the safety and tolerability of combination therapy with Albuvirtide (ABT) and 3BNC117 in virologically suppressed subjects with HIV-1 infection and explore the potential of viral suppression and viral reservoir clearance after analytical treatment interruption (ATI).

Detailed Description

This is an open-label, one site study, in which a total of 24 HIV-1 subjects who are virologically suppressed and stable on daily oral combination antiretroviral therapy will be enrolled.

All eligible patients will be switched from daily oral combination antiretroviral regimen to treatment of ABT and 3BNC117 for 14 weeks. There is a two-week overlap of the baseline oral antiretroviral therapy and the ABT-3BNC117 combination regimen at the beginning of the study treatment, and then the oral ART will be interrupted.

The patients will be monitored for viral rebound every two or four weeks following initiation of ABT-3BNC117 combination and will re-initiate an oral antiretroviral regimen if virological rebound is confirmed with plasma HIV-1 RNA levels above 200 copies/ml on two consecutive test.

Pharmacokinetics of ABT and 3BNC117 will be assessed in this study.

Conditions

HIV/AIDS

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Early treatment of infection

HIV-1 infected subjects initiated a stable combination antiretroviral therapy (ART) within 6 months of primary HIV infection (PHI), and had plasma HIV-1 RNA <50 copies/mL for at least 12 months.

Albuvirtide 0.32 g and 3BNC117 2 g every 2 weeks IV infusion for a total of 14 weeks.

Group Type: EXPERIMENTAL

Albuvirtide

Intervention Type: DRUG

Long-Acting HIV-1 Fusion Inhibitor (chemically modified peptide targeting HIV-1 gp41)

3BNC117

Intervention Type: DRUG

Recombinant, fully human mAb of the IgG1κ isotype that specifically binds to HIV-1 gp120.

Chronic period of infection treatment

Chronically HIV-1 infected subjects initiated a stable combination antiretroviral therapy (ART) after 6 months of primary HIV infection (PHI), and had plasma HIV-1 RNA <50 copies/mL for at least 12 months.

Albuvirtide 0.32 g and 3BNC117 2 g every 2 weeks IV infusion for a total of 14 weeks.

Group Type: EXPERIMENTAL

Albuvirtide

Intervention Type: DRUG

Long-Acting HIV-1 Fusion Inhibitor (chemically modified peptide targeting HIV-1 gp41)

3BNC117

Intervention Type: DRUG

Recombinant, fully human mAb of the IgG1κ isotype that specifically binds to HIV-1 gp120.

Interventions

Albuvirtide

Long-Acting HIV-1 Fusion Inhibitor (chemically modified peptide targeting HIV-1 gp41)

Intervention Type: DRUG

3BNC117

Recombinant, fully human mAb of the IgG1κ isotype that specifically binds to HIV-1 gp120.

Intervention Type: DRUG

Other Intervention Names

ABT

Eligibility Criteria

Inclusion Criteria

1. Males and females, age ≥18 years

2. For cohort 1: HIV-1 infected subjects initiated a stable combination antiretroviral therapy (ART) within 6 months of primary HIV infection (PHI), having the document evidence of initial diagnosis of HIV-1 infection and initiation of ART therapy within 6 months of PHI.

For cohort 2: Chronically HIV-1 infected subjects initiated a stable combination antiretroviral therapy (ART) after 6 months of primary HIV infection (PHI), having the document evidence of initial diagnosis of HIV-1 infection and initiation of ART therapy after 6 months of PHI.

3. Plasma HIV-1 RNA <50 copies/mL for at least 12 months prior to Screening Visit. An exception for a recorded HIV-1 RNA "blip" (e.g., transient HIV-1 RNA >50 copies/mL) can be considered.

4. Plasma HIV-1 RNA <20 copies/mL at Screening Visit.

5. CD4 cell count >500 cells/µL.

6. Laboratory values at Screening of:

1. Absolute neutrophil count (ANC) ≥0.75×10∧9/L;

2. Hemoglobin (Hb) ≥105 g/L (male) or ≥95 g/L (female);

3. Platelets ≥75×10∧9/L;

4. Serum alanine transaminase (SGPT/ALT) < 2 x upper limit of normal (ULN)

5. Serum aspartate transaminase (SGOT/AST) < 2 x ULN

6. Bilirubin (total) <2.5 x ULN unless Gilbert's disease is present or subject is receiving atazanavir in the absence of other evidence of significant liver disease

7. Creatinine ≤1.5 x ULN

7. Clinically normal resting 12-lead ECG at Screening Visit or, if abnormal, considered not clinically significant by the Principal Investigator.

8. Both male and female patients and their partners of childbearing potential must agree to use accepted methods of contraception.

9. Females of childbearing potential must have a negative serum pregnancy test at Screening visit and negative urine pregnancy test prior to receiving the first dose of study drug.

10. Subjects who have two or more potential alternative antiretroviral treatment regimens.

11. Willing and able to participate in all aspects of the study, including use of IV medication, completion of evaluations, attendance at scheduled clinic visits, and compliance with all protocol requirements as evidenced by providing written informed consent.

Exclusion Criteria

1. Any active infection or malignancy requiring acute therapy.

2. Hepatitis B infection as manifest by the presence of Hepatitis B surface antigen (HBsAg).

3. Hepatitis C infection as manifest by positive anti-HCV antibody and positive HCV RNA assay at the time of screening.

4. Females who are pregnant, lactating, or breastfeeding, or who plan to become pregnant during the study

5. Unexplained fever or clinically significant illness within 1 week prior to the first study dose

6. Any vaccination within 2 weeks prior to the first study dose.

7. Subjects BMI<20 or >27 kg/m∧2 [BMI＝weight/height∧2].

8. History of Bleeding Disorder or patients on anti-coagulant therapy

9. Participation in an experimental drug trial(s) within 30 days of the Screening Visit

10. Any known allergy or antibodies to the study drug or excipients

11. Treatment with any of the following:

1. Radiation or cytotoxic chemotherapy with 30 days prior to the screening visit

2. Receipt of any fusion inhibitor and monoclonal antibody therapy of any kind in the past.

3. Immunosuppressants within 60 days prior to the Screening Visit

4. Immunomodulating agents (e.g., interleukins, interferons), hydroxyurea, or foscarnet within 60 days prior to the screening visit

5. Oral or parenteral corticosteroids within 30 days prior to the Screening Visit. Subjects on chronic steroid therapy > 5 mg/day will be excluded with the following exception:

6. Subjects on inhaled, nasal, or topical steroids will not be excluded

12. Any other clinical condition that, in the Investigator's judgment, would potentially compromise study compliance or the ability to evaluate safety/efficacy.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Frontier Biotechnologies Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cheng Yao

Role: STUDY_DIRECTOR

Frontier Biotechnologies Inc.

Locations

Peking Union Medical College Hospital

Beijing, , China

Countries

China

Central Contacts

Xingxiang Xu

Role: CONTACT

xxxu@frontierbiotech.com

025-69648410

Cheng Yao

Role: CONTACT

yaocheng@frontierbiotech.com

Facility Contacts

Taisheng Li, M.D.

Role: primary

litsh@263.net

Other Identifiers

ABT-3BNC117_202

Identifier Type: -

Identifier Source: org_study_id