Phase III Clinical Study of Azvudine in Hiv-infected Treatment Naive Patients

Study Overview
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Brief Summary
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Azvudine,(FNC)， new nuclear nucleoside reverse transcriptase inhibitors, FNC make itself a better candidate to be co-formulated in other anti-HIV therapies, thus to improve patient's compliance, approved by state drug administration (NMPA) for clinical research. FNC has completed its phase I、II clinical studies with desirable results.This is a multi-center, randomized, double-blind,double-placebo,active-control clinical trial. Subjects in experimental arm receives FNC+TDF+EFV+3TC placebo, while the subjected in active control arm receives 3TC+TDF+EFV+FNC placebo. The background drugs in both arms are conducted in open-label design while FNC and 3TC are conducted in double-blinded design.

Official Title
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A Randomized, Double-blind, Double-simulated, Active-controlled，Phase III Clinical Study Evaluating the Efficacy and Safety of Azvudine Combined With Tenofovir Fumarate and Efavirenz in Hiv-infected Treatment Naive Patients

Conditions
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HIV-infection/Aids

Intervention / Treatment
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* Drug: FNC
* Drug: 3TC
* Drug: TDF
* Drug: EFV
* Drug: FNC placebo
* Drug: 3TC placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-65 years old, regardless of gender; Participant must have an positive HIV test; Have not received anti-HIV treatment; HIV-1 RNA≥1000 copies/ml and the investigators determined that the subjects were eligible for HAART therapy. Who have no recent family planning and agree to take effective non-drug contraceptive measures during the trial period and within 3 months after the end of administration; The subjects could fully understand the purpose, nature, method and possible adverse reactions of the test, and voluntarily participate in and sign the informed consent. Exclusion Criteria: History of allergy to any ingredient or excipient of the research drug or have a high sensitivity constitution; Patients with severe opportunistic infection or tumor; Clinically Hepatitis b surface antigen/hepatitis c antibody positive; Clinically Alanine transaminase and/or alanine transaminase ≥5× normal upper limit (ULN); Clinically Alanine aminotransferase ≥3×ULN and total bilirubin ≥2×ULN (direct bilirubin/total bilirubin > 35%); Glomerular filtration rate < 70ml/min/1.73m2 (calculated by ckd-epi Creatinine 2009 Equation), or Creatinine ≥ULN; Clinically significant diseases serious chronic diseases , metabolic diseases (such as diabetes), neurological and psychiatric diseases; History of pancreatitis; Women in pregnancy and breastfeeding; History of drug abuse, alcohol abuse and drug abuse; Participating in clinical trials of other drugs within the first three months of screening; Other factors considered inappropriate by the investigator to be included in the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FNC Treatment Group<br>FNC 3mg, 1 tablet;TDF 300mg, 1 tablet;EFV 200mg, 2 tablets;3TC placebo 1 tablet;daily oral before bedtime | Drug: FNC<br>* 3mg, 1 tablet，QD<br>* Other names: Azvudine;Drug: TDF<br>* 300mg, 1 tablet，QD<br>* Other names: Tenofovir Fumarate;Drug: EFV<br>* 200mg, 1 tablet，QD<br>* Other names: Efavirenz;Drug: 3TC placebo<br>* 1 tablet，QD<br>* Other names: Lamivudine placebo;|
| Active Comparator: 3TC control group<br>3TC 300mg, 1 tablet;TDF 300mg, 1 tablet;EFV 200mg, 2 tablets;FNC placebo 1 tablet;daily oral before bedtime | Drug: 3TC<br>* 300mg, 1 tablet，QD<br>* Other names: Lamivudine;Drug: TDF<br>* 300mg, 1 tablet，QD<br>* Other names: Tenofovir Fumarate;Drug: EFV<br>* 200mg, 1 tablet，QD<br>* Other names: Efavirenz;Drug: FNC placebo<br>* 1 tablet，QD<br>* Other names: Azvudine placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of subjects with plasma HIV-1 Ribonucleic acid (RNA) <50 copies/milliliter (c/mL) at Week 48 | Rate of participants with a HIV-1 RNA < 50 copies per mL .If HIV RNA level is < 50 copies per mL at Week 48, it is considered as virologic success as per the snapshot approach. | 48 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of subjects with plasma HIV-1 Ribonucleic acid (RNA) <50 copies/milliliter (c/mL) at Week 24 and Week 96 | Rate of participants with a HIV-1 RNA < 50 copies per mL at Week 24 and Week 96 | Week 24 and Week 96 | 
| Rate of subjects with plasma HIV-1 Ribonucleic acid (RNA) <400 copies/milliliter (c/mL) at Week 24 ，Week 48 and Week 96； | Rate of participants with a HIV-1 RNA < 50 copies per mL at Week 24，Week 48 and Week 96 | Week 24 and Week 48 and Week 96, | 
| Change of CD4+ cell count from baseline at Week 48 and Week 96 | The immunologic change was determined by changes in Cluster of CD4+ cell count. Change from baseline in CD4+ cell count at Weeks 48 and 96 were assessed | Week 48 and Week 96 | 
| Time to achieve virologic failure（HIV-1 RNA<50 copies/ml） | Time to HIV-1 RNA<50 copies/ml from baseline | Baseline and Week 96 | 
| Diachronic change of logarithm (log) HIV-RNA reduction from baseline | The Diachronic change of logarithm (log) HIV-RNA change was determined by changes in Cluster of logarithm (log) HIV-RNA count. Change from baseline in logarithm (log) HIV-RNA at Weeks 96 were assessed | Baseline and Week 96 | 
| Diachronic change of CD4+T、 CD8+T cell count from baseline | The immunologic change was determined by changes in Cluster of CD4+ cell count. Change from baseline in CD4+ cell count to Weeks 96 were assessed | Baseline and Week 96 | 
| Safety outcome of subjects at Week 48 and Week 96。 | Rate of participants discontinuing therapy due to AEs were reported. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. | Week 48 and Week 96 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FNC, HIV-infection, Aids