Efficacy and Safety of ACC017 Tablets Compared With Dolutegravir Sodium Tablets in Treatment-Naïve Adults With Human Immunodeficiency Virus Type 1 (HIV-1)

Official title

A Multicenter, Randomized, Double-Blind, Double-Dummy, Dolutegravir Sodium Tablets Controlled, Phase III Study to Evaluate the Efficacy and Safety of ACC017 Tablets in Treatment-Naïve Adults With Human Immunodeficiency Virus Type 1 (HIV-1)

Overview

This study employs a multicenter, randomized, double-blind, double-dummy, active-controlled, parallel-group, non-inferiority design. The trial will be conducted in treatment-naïve adult patients with HIV-1, using Dolutegravir Sodium Tablets as the control, to demonstrate the efficacy and safety of the core investigational drug ACC017 combined with FTC/TAF Tablets (II) compared to Dolutegravir Sodium combined with FTC/TAF Tablets (II) in treating treatment-naïve adult HIV-1 patients. After initial screening eligibility is confirmed, participants will return to the clinic on Day 1 (D1) for re-evaluation of eligibility and completion of required examinations. Eligible participants will be randomized in a 1:1 ratio to receive either ACC017 Tablets (40 mg, once daily \[QD\]) or Dolutegravir Sodium Tablets (50 mg, QD). Both treatment groups will also receive FTC/TAF Tablets (II) and will undergo 48 weeks of continuous double-blind treatment. Subsequently, all study participants will transition to open-label treatment with ACC017 combined with FTC/TAF Tablets (III) for an additional 48 weeks (during which the dummy medication will no longer be administered).

Interventions

• Drug ACC017+FTC/TAF
  ACC017+Emtricitabine/Tenofovir Alafenamide
• Drug DTG+FTC/TAF
  Dolutegravir+Emtricitabine/Tenofovir Alafenamide

Primary outcome measures

• At 48 weeks of treatment, the percentage of participants with HIV RNA load <50 copies/mL (analyzed using the US FDA Snapshot Approach) (primary analysis). [Time frame: week 48]

Secondary outcome measures (12)

• Percentage of participants with HIV RNA < LLOQ at Week 48; [Time frame: week 48]
• Percentage of participants with HIV RNA <200 copies/mL at Week 48; [Time frame: week 48]
• Percentage of participants with HIV RNA <50 copies/mL at Week 24; [Time frame: week 24]
• Percentage of participants with HIV RNA < LLOQ at Week 24; [Time frame: week 24]
• Absolute change from baseline in log10-transformed HIV RNA at Week 4; [Time frame: week 4]
• Absolute change from baseline in log10-transformed HIV RNA at Week 8; [Time frame: week 8]
• Absolute change from baseline in log10-transformed HIV RNA at Week 12; [Time frame: week 12]
• Percentage of participants with HIV RNA <50 copies/mL at Week 96 (final analysis); [Time frame: week 96]
• Percentage of participants with HIV RNA < LLOQ at Week 96. [Time frame: week 96]
• Absolute change from baseline in CD4+ cell count at Week 48 (cells/μL); [Time frame: week 48]
• Percentage of participants with an increase from baseline in CD4+ cell count of ≥100 cells/μL or ≥30% at Week 48; [Time frame: week 48]
• Absolute change from baseline in CD4+ cell count at Week 96 (cells/μL). [Time frame: week 96]

Eligibility criteria

Inclusion criteria

A participant will be excluded from the trial if they meet any one or more of the following criteria:

• Voluntarily sign the written informed consent form, demonstrate the ability to understand and comply with the requirements of the study protocol;
• Age ≥18 years (inclusive) at the time of providing informed consent, both male and female participants are eligible;
• Diagnosed with HIV infection prior to informed consent, and have an HIV RNA viral load ≥500 copies/mL (tested at the local center) at screening;
• Have not received any ART since initial HIV diagnosis, and agree not to initiate any ART from the time of informed consent until randomization.

Exclusion criteria

• Participants judged by the investigator as having poor treatment compliance or protocol adherence, or any other condition making them unsuitable for the study, or when participation may not best protect the participant's health interests;
• At screening, female participants who are pregnant, breastfeeding, or have a positive blood pregnancy test; or from 1 month before screening until 3 months after the last dose of the investigational product, participants of childbearing potential (WOCBP) or male participants with plans for procreation (including egg or sperm donation), or unwilling to use effective contraception (including one or more non-pharmacological methods, or absence of heterosexual activity in daily life) or safety measures;
• At screening, judged by the investigator to be in the acute phase of HIV-1 infection, or with opportunistic infections or other clinically significant AIDS-defining conditions within 3 months before screening;
• At screening, judged by the investigator to have poorly controlled clinically significant diseases (including cardiovascular, respiratory, digestive, endocrine-metabolic, neuropsychiatric, hematological, and immune systems, etc.), including but not limited to: poorly controlled hypertension despite active treatment (resting SBP ≥160 mmHg or DBP ≥100 mmHg upon retest), NYHA Class III or IV cardiac function, GOLD Grade 3-4 COPD, severe liver impairment (Child-Pugh Class C), etc.;
• At screening, judged by the investigator to have clinically significant laboratory abnormalities, including but not limited to: hemoglobin (Hb) <90 g/L, or ALT >5 × ULN, or ALT >3 × ULN with total bilirubin (TBIL) >1.5 × ULN, or creatinine clearance <30 mL/min (CKD-EPI equation);
• At screening, HBsAg-positive with HBV DNA ≥2000 IU/mL (local center testing), HCV antibody-positive with HCV RNA > LLOQ (local center testing), or judged by the investigator to require anti-syphilis treatment (participants who have completed standardized anti-syphilis treatment for ≥7 days may be considered);
• Use of pre-exposure prophylaxis (PrEP) and/or post-exposure prophylaxis (PEP) within 1 month before screening, or prior use of long-acting PrEP drugs (e.g., cabotegravir or lenacapavir, etc.);
• Within 30 days before screening, at screening, or planned use during the trial, systemic immunomodulators, cytotoxic drugs, etc. (see Appendix 7), and unwilling or unable to discontinue use from the time of informed consent;
• At screening, known history of allergy to the investigational product, structurally related drugs, or excipients; or history of allergic diseases requiring medication control before screening (e.g., asthma, urticaria, atopic dermatitis \[eczema\], etc.);
• Before screening, major gastrointestinal surgery (except uncomplicated appendectomy or cholecystectomy); or at screening, judged by the investigator as likely to require elective major surgery during the trial;
• Within 5 years before screening, history of malignancy (except carcinoma in situ of the cervix treated by conization, or surgically cured basal cell carcinoma, squamous cell carcinoma, and/or carcinoma in situ \[Bowen's disease\] of the skin);
• Within 5 years before screening, history of alcohol, drug, or other substance abuse (non-medical excessive, inappropriate, or addictive use of alcohol, drugs, or other substances leading to social, psychological, or physiological impairment);
• Before or at screening, intolerance to venipuncture, history of needle or blood phobia, or blood donation (including component blood) or significant blood loss (≥400 mL) or transfusion within 3 months before screening, or plans to donate blood during the trial;
• Participation in any interventional clinical trial (including drugs, vaccines, or devices) within 3 months before screening.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

China · 1 center

• Beijing Ditan Hospital Capital Medical University, Beijing, China — Beijing

Identifiers

NCT: NCT07711223 · ADYY-ACC017-301

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗