- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05493969
Efficacy and Tolerability of DTG Plus 3TC in HIV Infected Adults With Virologically Suppression and TDF Toxicity
A Study Evaluating the Efficacy and Tolerability of Dolutegravir Plus Lamivudine in HIV Infected Adults Who Are Virologically Suppressed and With Evidence of TDF Toxicity
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Anticipated)
Phase
- Phase 4
Contacts and Locations
Study Contact
- Name: Renfang Zhang
- Phone Number: +86-18916051096
- Email: zhangrenfang@shaphc.org
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Female subjects were required to meet one of the following criteria: 1) Incapacitated, defined as postmenopausal (spontaneous amenorrhea at 12 months, age ≥45 years) or physically unable to conceive after tubal ligation, hysterectomy, or bilateral oophorectomy; 2) Have potential to have children, but are negative at screening and on day 1 pregnancy test, and agree to use appropriate contraceptive methods, including oral contraceptives, condoms and intrauterine devices;
- At least once plasma HIV-1 RNA<40 c/mL in the 6 months prior to screening and plasma HIV-1 RNA <40 c/mL at screening;
- Must be on uninterrupted TDF + 3TC/FTC-based regimen for ≥6 months prior to screening;
Participants with pre-existing clinical manifestations of TDF related adverse reactions at the time of screening.
TDF-related renal damage was defined as: meeting 1 of the 5 following conditions in the investigator's judgement, based upon the medical history and relevant examinations, likely to represent TDF toxicity:
i. eGFR decrease by 5 mL/min per year for at least 3 consecutive years or confirmed 25% eGFR decline from baseline ii. Urine β2-microglobulin/Cr ≥300 μg/g iii. Urine microalbumin/creatinine >30 μg/mg iv. Non-diabetic glycosuria (urine glucose 1+ or above) v. Serum phosphate <0.8 mmol/L TDF - associated bone toxicity is defined as a T-value less than -1.0 or Z- value less than -2.0 or fragility fracture after TDF/XTC use and other factors is excluded according to the medical history and relevant examination.
- Sign the informed consent and be able to visit regularly according to the test requirements.
Exclusion Criteria:
- Women who are pregnant or breastfeeding or plan to become pregnant or breastfeed during the study;
- Participants with AIDS-related opportunistic infections or AIDS-related or unrelated neoplastic diseases;
- Patients with ALT >= 5 x ULN, or ALT >=3 x ULN and bilirubin >= 1.5xULN (with >35% direct bilirubin. Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- Evidence of Hepatitis B virus (HBV) infection: Participants positive for HBsAg, negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and positive for HBV DNA are excluded.
- Hepatitis C virus (HCV) infection;
- Participants who are allergic or intolerant to lamivudine or dolutegravir;
- Participants with known previous episodes of virologic failure and known resistance mutations of 3TC or INSTI if resistance mutations had previously been identified;
- Taking medications that contraindicated with lamivudine or dolutegravir; Other conditions that the investigator considers unsuitable to participate in the study, including the risk of suicide, poor adherence, and interference with the evaluation of clinical study endpoints.
- Participants with creatinine clearance <30ml/min.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: DTG/3TC
Subjects will switch to dolutegravir (DTG) plus lamivudine (3TC) or fixed dose combination DTG/3TC for 48 weeks.
|
Subjects will discontinue their TDF + 3TC/FTC-based regimen and will switch to DTG+3TC or fixed dose combination DTG/3TC.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Virologic outcomes
Time Frame: Week 48
|
Percentage of participants with virologic failure after 48 weeks of treatment by FDA Snapshot algorithm.
|
Week 48
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
HIV-RNA
Time Frame: Week 24 and Week 48
|
Percentage of participants with HIV-RNA <40 copies/mL at weeks 24 and 48
|
Week 24 and Week 48
|
CD4 counts
Time Frame: Week 24 and Week 48
|
Changes from Baseline in CD4+ Cell Counts at Week 24 and 48
|
Week 24 and Week 48
|
bone markers
Time Frame: Week 48
|
Median percentage improvement (±SD) of circulating bone markers (alkaline phosphatase, osteocalcin, 25-OH-vitamin D level) at 24 weeks and 48 weeks after switch vs baseline)
|
Week 48
|
DEXA
Time Frame: Week 48
|
Percentage change of T-score classification (normal, osteopenia and osteoporosis) or Z-score classification (normal, abnormal) of bone mineral density using DEXA at 48 weeks after switch vs baseline
|
Week 48
|
renal markers
Time Frame: Week 24 and Week 48
|
Median percentage improvement (±SD) of urine microalbumin , serum CysC, urine β2-microglobulin/creatinine, urine N-Acetyl-Beta-D-Glucosaminidase (NAG), serum retinol binding protein (RBP) at 24 weeks and 48 weeks after switch vs baseline
|
Week 24 and Week 48
|
eGFR
Time Frame: Week 24 and Week 48
|
Median percentage improvement (±SD) of eGFR and Percentage change of renal function (normal, mild, moderate and severe) at 24 weeks and 48 weeks after switch vs baseline
|
Week 24 and Week 48
|
Collaborators and Investigators
Investigators
- Study Chair: Renfang Zhang, Shanghai Public Health Clinical Center
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Lentivirus Infections
- Retroviridae Infections
- Immune System Diseases
- Slow Virus Diseases
- HIV Infections
- Acquired Immunodeficiency Syndrome
- Immunologic Deficiency Syndromes
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Reverse Transcriptase Inhibitors
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Anti-HIV Agents
- Anti-Retroviral Agents
- HIV Integrase Inhibitors
- Integrase Inhibitors
- Lamivudine
- Dolutegravir
Other Study ID Numbers
- 2432
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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