Clinical trial NCT02369965: Test Albuvirtide in Experienced Patients
Official title: Efficacy and Safety of Albuvirtide for Injection Combined With LPV/r for Treatment of HIV-1-Infected Patients Failed First-line Antiretroviral Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
AIDS
Keywords: HIV-1
AIDS
Albuvirtide
Treatment-experienced
Fusion inhibitor
Lead sponsor: Frontier Biotechnologies Inc.
Sponsor class: INDUSTRY
First posted: 2015-02-24
Enrollment: 418
Sex: ALL
Minimum age (years): 16
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of albuvirtide combined with lopinavir-ritonavir (LPV/r) in HIV-1-infected patients who failed first-line antiretroviral therapy (ART).

Detailed description: This was a 48-week, multi-center, open-label, randomized and controlled, non-inferiority phase 3 clinical trial to evaluate the safety and efficacy of albuvirtide combined with LPV/r in HIV-1 infected patients who failed their first-line ART and had HIV-1 RNA levels ≥ 1000 copies/mL at screening.

The trial was conducted in 12 sites in China. Subjects meeting inclusion criteria were randomized in a 1:1 ratio to ABT group and NRTI group, in which the ABT group received albuvirtide and LPV/r combination therapy, and NRTI group received the standard 3-drug regimen of LPV/r + Lamivudine (3TC) + Tenofovir (TDF). If TDF was used in the previous regimen or genotypic resistance histories showed primary mutation to TDF, zidovudine (AZT) or abacavir (ABC) would be used. Albuvirtide was given by weekly intravenous infusion and LPV/r was given twice daily orally. A total of 418 subjects were randomized, of whom 401 received at least one treatment.

Eligibility criteria: Inclusion Criteria:

1. 16-60 years old, male or female.
2. Those who meet the Diagnostic Criteria of AIDS and HIV Infection, the Health Industry Standard of the People's Republic of China (WS 293-2008).
3. Those who have been undergoing antiretroviral treatment with nucleosides and non-nucleoside reverse transcriptase inhibitors (NRTIs+NNRTIs) for at least 6 months.
4. HIV-RNA ≥ 1000 copies/mL.
5. Those who have no serious hepatic or renal functional impairment and other parameters are generally in the normal ranges according to the comprehensive physical examinations (including general physical examination, routine blood and urine tests, blood chemistry tests, ECG, etc.).
6. The subjects should have a full understanding of the objective, nature, methods of the trial and the possible reactions. He/She should participate in the trial voluntarily and should sign the informed consent form.

Exclusion Criteria:

1. Those who are in an acute stage of infection, or have suffered from AIDS-related diseases (e.g. opportunistic infections or malignant tumors, etc.) at enrollment; or have suffered from opportunistic infections within 3 months prior to enrollment and the conditions have not reached a stable state within 2 weeks prior to enrollment.
2. Those who have used protease inhibitors or HIV fusion inhibitors for antiretroviral treatment, and who have participated in HIV vaccine clinical trials or have participated in other drug trials within recent 3 months.
3. Those who have been co-administered antiviral treatment for hepatitis.
4. Those whose screening test results meet one of the following: hemoglobin \< 9 g/dL, WBC count \<2×109/L, neutrophil count \< 1×109/L, PLT count \< 75×109/L, transaminase \> 3×ULN, total bilirubin \> 2×ULN, creatinine \> 1×ULN, serum creatine phosphokinase \> 2×ULN.
5. Those with allergic constitution or known allergic to ingredients of the investigational drug or ART drugs prescribed in the protocol.
6. Currently suffering from serious chronic diseases, metabolic diseases (such as diabetes mellitus), neurological and psychiatric disorders.
7. Patients with hemophilia A or B.
8. Those with suspected or confirmed history of alcohol or drug abuse.
9. Pregnant or lactating women; or women of childbearing age who refuse to take contraceptive measures during the trial.
10. Those for whom the possibility of being enrolled is low according to the judgment of the investigator (e.g. weak physical condition, poor compliance, etc.).

Primary outcomes:
measure: Percentage of participants of virological suppression at Week 48
timeFrame: Through Week 48
Secondary outcomes:
measure: Changes of viral load
timeFrame: Baseline to Week 48
measure: Percentage of participants with HIV-1 RNA < 400 copies/mL at Week 48
timeFrame: Through Week 48
measure: Changes of CD4 cell count
timeFrame: Baseline to Week 48
Other outcomes:
Locations:
city: Beijing
country: China
facility: 302 Hospital People's Liberation Army Of China
state: Beijing
city: Beijing
country: China
facility: Beijing Ditan Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing Youan Hospital, Capital medical university
state: Beijing
city: Guangzhou
country: China
facility: Guangzhou Eighth People's Hospital
state: Guangdong
city: Shenzhen
country: China
facility: The Third People'S Hospital Of Shenzhen
state: Guangdong
city: Zhengzhou
country: China
facility: Henan Infectious Disease Hospital
state: Henan
city: Changsha
country: China
facility: The First Hospital of Changsha
state: Hunan
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: Shanghai
country: China
facility: Shanghai Public Health Clinical Center
state: Shanghai
city: Xi'an
country: China
facility: Tangdu Hospital, Fourth Military Medical University
state: Shanxi
city: Hangzhou
country: China
facility: Affiliated Hangzhou Xixi Hospital,Zhejiang University School Of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: The First Affiliated Hospital Zhejiang University School Of Medicine
state: Zhejiang
Study officials:
affiliation: Frontier Biotechnologies Inc.
name: Dong Xie
role: STUDY_DIRECTOR
References:
citation: Su B, Yao C, Zhao QX, Cai WP, Wang M, Lu HZ, Chen YY, Liu L, Wang H, He Y, Zheng YH, Li LH, Chen JF, Yu JH, Zhu B, Zhao M, Sun YT, Lun WH, Xia W, Sun LJ, Dai LL, Jiang TY, Wang MX, Zheng QS, Peng HY, Wang Y, Lu RJ, Hu JH, Xing H, Shao YM, Xie D, Zhang T, Zhang FJ, Wu H; TALENT Study Team. Efficacy and safety of the long-acting fusion inhibitor albuvirtide in antiretroviral-experienced adults with human immunodeficiency virus-1: interim analysis of the randomized, controlled, phase 3, non-inferiority TALENT study. Chin Med J (Engl). 2020 Nov 25;133(24):2919-2927. doi: 10.1097/CM9.0000000000001273.