Safety of tenofovir alafenamide (TAF) in patients who developed kidney toxicity while receiving tenofovir disoproxil fumarate (TDF)

Phase 1

Conditions: MedDRA version: 20.1Level: PTClassification code 10020161Term: HIV infectionSystem Organ Class: 10021881 - Infections and infestations
HIV infection
Therapeutic area: Diseases [C] - Virus Diseases [C02]

Registration Number: EUCTR2016-003345-29-GB

Lead Sponsor: Kings College Hospital NHS Foundation Trust

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 40

Inclusion Criteria

Subjects must meet all the following inclusion criteria to be eligible for participation in this study
•Age = 16 years
•Documented HIV-1 antibody test
•Able to give informed consent
•Documented history of TDF-induced acute tubular injury on renal biopsy which was not explained by other factors, or TDF-induced treatment-limiting tubulopathy, defined by at least 2 of the following:
oProteinuria of =1+ on urinary dipstick (or protein/creatinine ratio >30 mg/mmol)
oGlycosuria of =1+ on urinary dipstick
oSerum phosphate <0.64 mmol/L
oRapid eGFR decline (>5 mL/min/1.73m2/year with >25% reduction from baseline)
•On stable antiretroviral therapy for preceding 6 months
•HIV RNA <200 copies/ml at the most recent visit
•Female patients of child-bearing potential (non-child-bearing potential is defined as 12 months of spontaneous amenorrhea in women = 45 years of age, documented tubal ligation, hysterectomy or bilateral oophorectomy) must agree to use contraception to avoid pregnancy.

Are the trial subjects under 18? yes
Number of subjects for this age range: 40
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion Criteria

Subjects who meet any of the exclusion criteria must not be enrolled in the study
Diabetes mellitus
Dipstick glucose =1+ at screening or baseline
Dipstick proteinuria >2+ or urine protein-creatinine ratio =100 mg/mmol at screening or baseline
Estimated glomerular filtration rate (eGFR) <30 mL/min, according to the Cockcroft Gault formula for creatinine clearance (CLcr) mL/min
Male=((140-age in years)×(weight in kg)×1.23)/(Serum creatinine (in µmol/L)
Female=((140-age in years)×(weight in kg)×1.04)/(Serum creatinine (in µmol/L)
Current use of tenofovir (TDF or TAF)
Screening laboratory parameters > grade 3 (ACTG criteria)
Current alcohol use (>3 units daily for the past month) or drug dependence which would make the participant unable to comply with the protocol (investigator opinion)
Significant co-morbidities (investigator opinion)
Current use of rifamycins (rifampicin or rifabutin)
Individuals unable or unwilling to comply with the requirements of the study (investigator opinion)

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the renal and bone safety of TAF in patients with a history of tubulopathy/Fanconi syndrome while receiving TDF<br><br>Primary endpoint<br>•Between study arm difference in change from baseline to week 12 in retinol-binding protein/creatinine ratio (RBPCR) <br><br>Secondary endpoints<br><br>•Incidence of tubulopathy in the TAF/FTC exposed population (through week 96) <br>•Between study arm difference in change from baseline in: <br>oRenal function and bone turnover markers (week 4, 12)<br>•Change from baseline in the TAF/FTC exposed population:<br>oRenal function and bone turnover markers (week 24, 48, 72, 96)<br>oBone mineral density (week 48, 96)<br>;Secondary Objective: N/A;Primary end point(s): Between study arm difference in the change from baseline to week 12 in retinol-binding protein/creatinine ratio (RBPCR). ;Timepoint(s) of evaluation of this end point: Between baseline and week 12

Secondary Outcome Measures