ACC017 is an integrase inhibitor that will be evaluated for the treatment of HIV infection. This phase Ib/IIa, randomized, double-blind, parallel, dose ranging, placebo-controlled 'proof of concept' study is designed to evaluate the safety, tolerability, pharmacokinetics and antiviral effect of ACC017 monotherapy and combined with FTC/TAF by sequency versus placebo in treatment-naïve HIV-1 infected adults. This study includes two stages, stage one is a single dose escalation, and all subjects will be co-administrated with FTC/TAF at 200 mg/25 mg on stage two. The study consists of a screening visit, baseline period, monotherapy period, and combination therapy period. Total 36 subjects will be randomized in a 5:1 ratio to receive one of three doses of ACC017 or placebo lasting for 10 days for monotherapy followed by 18 days for combination therapy.
This phase Ib/IIa study in HIV-infected antiretroviral naive adult subjects is conducted to evaluate the safety, tolerability, pharmacokinetics and antiviral effect of ACC017 tablet as monotherapy/combination with NRTIs and to explore the recommended dose for the future pivotal clinical trial of ACC017. The study will be conducted as two stages. Stage one will includes a dose-ranging evaluation of ACC017 5mg, 40mg and 80mg once daily compared to placebo on the basis of safety, tolerability, pharmacokinetics and antiviral activity. Subjects will be randomized in a 5:1 ratio to receive one of three doses of ACC017 or placebo. Each subject will receive ACC017 tablet as monotherapy for 10 days and then followed by a combination with NRTIs for 18 days. In monotherapy, the enrolment into the next higher dose group will commence only when investigator and sponsor both agree that ACC017 is safe and well tolerated at a given dose. Stage two is open and subjects will continue to take ACC017 at the dose given on stage one in combination with FTC/TAF tablet at 200 mg/25 mg once daily for 18 days. Subjects randomized to receive placebo in stage one will receive the equivalent dose of ACC017 combined with FTC/TAF.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
36
ACC017+FTC/TAF
Placebo
Beijing Ditan Hospital, Capital Medical University
Beijing, China
Report the incidence, severity and seriousness of adverse events, and the relationship between drug and AE
Report the incidence, severity and seriousness of adverse events, and the relationship between drug and AE
Time frame: Day 1- Day 11
HIV-1 RNA viral load change from baseline
HIV-1 RNA viral load change from baseline
Time frame: Day 11
Proportion of patients with HIV-1 RNA viral load <50 copies/mL
Proportion of patients with HIV-1 RNA viral load \<50 copies/mL
Time frame: Day 29
Pharmacokinetics parameter: Cτ,ss
Cτ,ss is defined as the steady-state plasma drug concentration at the end of the dosing interval after the last administration of a given dose on the monotherapy and combination therapy periods.
Time frame: Day 10, Day 29
Pharmacokinetics parameter: Cmin,ss
Cmin,ss is defined as the minimum steady-state plasma drug concentration after the last dose of monotherapy.
Time frame: Day 10
Pharmacokinetics parameter: Cmax,ss
Cmax,ss is defined as the maximum steady-state plasma drug concentration after the last dose of monotherapy.
Time frame: Day 10
Pharmacokinetics parameter: AUC0-τ,ss
AUC0-τ,ss is defined as the steady-state area under the plasma concentration-time curve from time zero to the any dosing interval of monotherapy.
Time frame: Day 1- Day 10
Pharmacokinetics parameter: Tmax,ss
Tmax,ss is defined as the time to reach steady-state maximum plasma concentration during monotherapy period.
Time frame: Day 1-Day 10
Pharmacokinetics parameter: MRT0-τ,ss
MRT0-τ,ss is defined as the steady-state mean residence time from time zero to any dosing interval of monotherapy.
Time frame: Day 1-Day 10
Changes over time in temperature of vital signs
Temperature in degree Celsius.
Time frame: Day 1-Day 29
Changes over time in pulse of vital signs
Pulse in beat per minute.
Time frame: Day 1-Day 29
Changes over time in systolic and diastolic blood pressure of vital signs
Systolic and diastolic blood pressure in millimeters (mm) of mercury (Hg).
Time frame: Day 1-Day 29
Changes over time in respiratory rate of vital signs
Respiratory rate in breaths per minute.
Time frame: Day 1-Day 29
Changes over time in heart rate as measured by electrocardiogram(ECG)
Heart rate in beat per minute.
Time frame: Day 1-Day 29
Changes over time in PR interval as measured by ECG
PR interval is measured by ECG.
Time frame: Day 1-Day 29
Changes over time in QRS duration
QRS duration is measured by ECG.
Time frame: Day 1-Day 29
Changes over time in QTc interval
QTc interval is measured by ECG.
Time frame: Day 1-Day 29
Changes over time in weight
Weight is in kilograms.
Time frame: Day 1-Day 29
Pharmacokinetics parameters: Cmax
The maximum drug concentration following the first dose of monotherapy.
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Time frame: Day 1-Day 2
Pharmacokinetics parameters: Cτ
The drug concentration on the end of the first dosing interval of monotherapy.
Time frame: Day 2
Pharmacokinetics parameters: AUC0-τ
AUC0-τ is defined as the area under the plasma concentration-time curve from time zero to the first dosing interval of monotherapy.
Time frame: Day 2
Pharmacokinetics parameters: Tmax
Time to reach the maximum drug concentration after the first dose of monotherapy.
Time frame: Day 1- Day 2
Pharmacokinetics parameters: MRT0-τ
MRT0-τ is defined as the steady-state mean residence time from time zero to the first dosing interval of monotherapy.
Time frame: Day 1- Day 2
Report the incidence, severity and seriousness of adverse events, and the relationship between drug and AE
Report the incidence, severity and seriousness of adverse events, and the relationship between drug and AE
Time frame: Day 11-Day 29
HIV-1 RNA viral load changes from baseline over time
HIV-1 RNA viral load changes from baseline over time
Time frame: Day 2-Day 4, Day 8-Day 11, Day 21, Day 29
Proportion of patients with HIV-1 RNA viral load <50 copies/mL
Proportion of patients with HIV-1 RNA viral load \<50 copies/mL
Time frame: Day 11
Proportion of patients with HIV-1 RNA viral load <200 copies/mL
Proportion of patients with HIV-1 RNA viral load \<200 copies/mL
Time frame: Day 11, Day 29
The proportion of patients with HIV-1 RNA viral load <400 copies/mL
The proportion of patients with HIV-1 RNA viral load \<400 copies/mL
Time frame: Day 11, Day 29
Changes in viral load from baseline to HIV-1 RNA viral load at nadir
Changes in viral load from baseline to HIV-1 RNA viral load at nadir
Time frame: Day 11
The proportion of nadir HIV-1 RNA <50 copies/mL
The proportion of nadir HIV-1 RNA \<50 copies/mL
Time frame: Day 11