Clinical trial NCT04819347: Albuvirtide in Combination With 3BNC117 in Virologically Suppressed Subjects With HIV-1 Infection
Official title: The Phase 2, Two Arms, One Site, Safety and Antiviral Activity of Combination Therapy With Albuvirtide and 3BNC117 in Virologically Suppressed Subjects With HIV-1 Infection After Analytical Treatment Interruption
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: HIV/AIDS
Lead sponsor: Frontier Biotechnologies Inc.
Sponsor class: INDUSTRY
First posted: 2021-03-26
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Proportion of participants (with sustained viral suppression at week 14) with HIV-1 RNA < 50 copies/mL at Week 26 (24 weeks after ATI)
timeFrame: Week 26
Secondary outcomes:
measure: Mean time to virologic rebound (HIV-1 RNA≥200 copies/mL) after ATI
timeFrame: up to 48 weeks
measure: Proportion of participants without experiencing virologic rebound (HIV-1 RNA<200 copies/mL) at Week 26 (24 weeks after ATI).
timeFrame: Week 26
measure: Proportion of participants with HIV-1 RNA < 50 copies/mL at Week 26 (24 weeks after ATI).
timeFrame: Week 26
measure: Mean change in CD4 cell count after ATI
timeFrame: up to 48 weeks
measure: Mean change in CD4/CD8 ration after ATI
timeFrame: up to 48weeks
measure: Frequency of emergence of new resistance mutations after virologic rebound
timeFrame: up to 48 weeks
measure: Mean time to achieving HIV-1 RNA < 50 copies/mL after experiencing virologic rebound
timeFrame: up to 48 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
Study officials:
affiliation: Frontier Biotechnologies Inc.
name: Cheng Yao
role: STUDY_DIRECTOR
References: