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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01818596




Registration number
NCT01818596
Ethics application status
Date submitted
22/03/2013
Date registered
26/03/2013

Titles & IDs
Public title
Open-label Safety Study of E/C/F/TAF (Genvoya®) in HIV-1 Positive Patients With Mild to Moderate Renal Impairment
Scientific title
A Phase 3 Open-label Safety Study of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Single-Tablet Regimen in HIV-1 Positive Patients With Mild to Moderate Renal Impairment
Secondary ID [1] 0 0
2013-000516-25
Secondary ID [2] 0 0
GS-US-292-0112
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV 0 0
HIV Infections 0 0
Condition category
Condition code
Infection 0 0 0 0
Acquired immune deficiency syndrome (AIDS / HIV)
Renal and Urogenital 0 0 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - E/C/F/TAF

Experimental: E/C/F/TAF - Participants will receive E/C/F/TAF for 144 weeks. Following Week 144, in countries where E/C/F/TAF is not available (except for the United Kingdom), participants will be given the option to continue in the study and receive E/C/F/TAF for another 48 weeks, or until the product becomes available through an access program, or until Gilead Sciences elects to discontinue the study in that country, whichever comes first.


Treatment: Drugs: E/C/F/TAF
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in the Estimated Glomerular Filtration Rate Calculated by the Cockcroft-Gault Formula (eGFR_CG) at Week 24
Timepoint [1] 0 0
Baseline; Week 24
Primary outcome [2] 0 0
Change From Baseline in eGFR Calculated by the Chronic Kidney Disease Epidemiology Collaboration Method Based on Cystatin C (eGFR_CKD-EPI,cysC) at Week 24
Timepoint [2] 0 0
Baseline; Week 24
Primary outcome [3] 0 0
Change From Baseline in eGFR Calculated by the CKD-EPI Method Based on Serum Creatinine (eGFR_CKD-EPI,Creatinine) at Week 24
Timepoint [3] 0 0
Baseline; Week 24
Secondary outcome [1] 0 0
Change From Baseline in Actual GFR (aGFR) of E/C/F/TAF for Participants Enrolled in the PK/PD Substudy
Timepoint [1] 0 0
Baseline; Week 2, 4, or 8; Week 24
Secondary outcome [2] 0 0
Percent Change From Baseline in C-type Collagen Sequence (CTX) at Weeks 24 and 48
Timepoint [2] 0 0
Baseline; Weeks 24 and 48
Secondary outcome [3] 0 0
Percent Change From Baseline in Procollagen Type 1 N-terminal Propeptide (P1NP) at Weeks 24 and 48
Timepoint [3] 0 0
Baseline; Weeks 24 and 48
Secondary outcome [4] 0 0
Percent Change From Baseline in Retinol Binding Protein (RBP) to Creatinine Ratio (µg/g) at Weeks 24, 48, 96, and 144
Timepoint [4] 0 0
Baseline; Weeks 24, 48, 96, and 144
Secondary outcome [5] 0 0
Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio (µg/g) at Weeks 24, 48, 96, and 144
Timepoint [5] 0 0
Baseline; Weeks 24, 48, 96, and 144
Secondary outcome [6] 0 0
Percentage of Participants Experiencing Adverse Events or Graded Laboratory Abnormalities
Timepoint [6] 0 0
Baseline up to Week 240 plus 30 days
Secondary outcome [7] 0 0
Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Weeks 24, 48, 96, and 144
Timepoint [7] 0 0
Weeks 24, 48, 96, and 144
Secondary outcome [8] 0 0
Pharmacokinetic (PK) Parameter: Cmax of TAF
Timepoint [8] 0 0
Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
Secondary outcome [9] 0 0
PK Parameter: Tmax of TAF
Timepoint [9] 0 0
Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
Secondary outcome [10] 0 0
PK Parameter: Clast of TAF
Timepoint [10] 0 0
Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
Secondary outcome [11] 0 0
PK Parameter: Tlast of TAF
Timepoint [11] 0 0
Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
Secondary outcome [12] 0 0
PK Parameter: ?z of TAF
Timepoint [12] 0 0
Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
Secondary outcome [13] 0 0
PK Parameter: AUCtau of TAF
Timepoint [13] 0 0
Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
Secondary outcome [14] 0 0
PK Parameter: t1/2 of TAF
Timepoint [14] 0 0
Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
Secondary outcome [15] 0 0
PK Parameter: AUCtau of Tenofovir Diphosphate (TFV-DP) in Peripheral Blood Mononuclear Cell (PBMC) for Participants Enrolled in PK/PD Sub-study
Timepoint [15] 0 0
Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
Secondary outcome [16] 0 0
Change From Baseline in the eGFR_CG at Weeks 48, 96, and 144
Timepoint [16] 0 0
Baseline; Weeks 48, 96, and 144
Secondary outcome [17] 0 0
Change From Baseline in eGFR_CKD-EPI,cysC at Weeks 48, 96, and 144
Timepoint [17] 0 0
Baseline; Weeks 48, 96, and 144
Secondary outcome [18] 0 0
Change From Baseline in eGFR_CKD-EPI,Creatinine at Weeks 48, 96, and 144
Timepoint [18] 0 0
Baseline; Weeks 48, 96, and 144

Eligibility
Key inclusion criteria
Key

Cohort 1 (treatment-experienced switch)

* Must not have a history of known resistance to elvitegravir (EVG), tenofovir disoproxil fumarate (TDF), or emtricitabine (FTC)
* Plasma HIV-1 RNA concentrations (at least two measurements) at undetectable levels (according to the local assay being used) in the 6 months preceding the screening visit and have HIV-1 RNA < 50 copies/mL at screening
* Estimated glomerular filtration rate (GFR) 30-69 mL/min according to the Cockcroft-Gault formula for creatinine clearance, using actual weight
* May be currently enrolled in Gilead studies GS-US-236-0102, GS-US-236-0103, and GS-US-216-0114, but will be eligible to enroll only after the Week 144 visit for that study is complete; or currently receiving Stribild® (STB) or atazanavir (ATV)/cobicistat (COBI) + Truvada (TVD) in Gilead studies GS-US-236-0104 or GS-US-216-0105, but will be eligible to enroll only after the Week 48 visit for that study is complete.

Cohort 2 (treatment-naive)

* Plasma HIV-1 RNA levels = 1,000 copies/mL at screening
* Screening genotype report provided by Gilead Sciences must show sensitivity to EVG, FTC, and TDF
* No prior use of any approved or investigational antiretroviral drug for any length of time, except the use for pre-exposure prophylaxis (PrEP), or post-exposure prophylaxis (PEP), up to 6 months prior to screening
* Estimated GFR 30-69 mL/min according to the Cockcroft Gault formula for creatinine clearance, using actual weight

All Cohorts:

All individuals must meet all of the following inclusion criteria to be eligible for participation in this study:

* The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
* CD4+ count of = 50 cells/µL
* Stable renal function: serum creatinine measurements to be taken at least once (within three months of screening)
* Cause of underlying chronic kidney disease (eg hypertension, diabetes) stable, without change in medical management, for 3 months prior to baseline
* Normal electrocardiogram (ECG)
* Hepatic transaminases (AST and ALT) = 5 x upper limit of normal (ULN)
* Total bilirubin = 1.5 mg/dL, or normal direct bilirubin
* Adequate hematologic function
* Serum amylase = 5 x ULN
* Females of childbearing potential must agree to utilize highly effective contraception methods (two separate forms of contraception, one of which must be an effective barrier method, or be non-heterosexually active, practice sexual abstinence) from screening throughout the duration of study treatment and for 30 days following the last dose of study drug
* Females who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing
* Males must agree to utilize a highly effective method of contraception during heterosexual intercourse throughout the study period and for 30 days following discontinuation of investigational medicinal product. A highly effective method of contraception is defined as two separate forms of contraception, one of which must be an effective barrier method, or males must be non-heterosexually active, or practice sexual abstinence

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* A new AIDS-defining condition (excluding CD4 cell count and percentage criteria) diagnosed within the 30 days prior to screening,with the exception of the first two bullet points
* Hepatitis C virus (HCV) antibody positive. Individuals who are HCV positive, but have a documented negative HCV RNA, are eligible
* Hepatitis B surface antigen (HBVsAg) positive
* Individuals receiving drug treatment for Hepatitis C, or individuals who are anticipated to receive treatment for Hepatitis C during the course of the study
* Individuals experiencing decompensated cirrhosis (eg, ascites, encephalopathy, etc.)
* Females who are breastfeeding
* Positive serum pregnancy test
* Have an implanted defibrillator or pacemaker
* Current alcohol or substance use judged by the Investigator to potentially interfere with study compliance
* A history of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma
* Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline
* Individuals on hemodialysis, other forms of renal replacement therapy, or on treatment for underlying kidney diseases (including prednisolone and dexamethasone)
* Individuals receiving ongoing therapy with any medications not to be used with EVG, COBI, FTC, or TAF or individuals with any known allergies to the excipients of E/C/F/TAF

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/03/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
18/07/2018
Sample size
Target
Accrual to date
Final
252
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Holdsworth House Medical Practice - Darlinghurst
Recruitment hospital [2] 0 0
Clinical Research Infectious Diseases Department- Alfred Hospital - Melbourne
Recruitment hospital [3] 0 0
Prahran Market Clinic - Prahran
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment postcode(s) [3] 0 0
3181 - Prahran
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
District of Columbia
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Massachusetts
Country [10] 0 0
United States of America
State/province [10] 0 0
Michigan
Country [11] 0 0
United States of America
State/province [11] 0 0
Minnesota
Country [12] 0 0
United States of America
State/province [12] 0 0
Missouri
Country [13] 0 0
United States of America
State/province [13] 0 0
New Jersey
Country [14] 0 0
United States of America
State/province [14] 0 0
New Mexico
Country [15] 0 0
United States of America
State/province [15] 0 0
New York
Country [16] 0 0
United States of America
State/province [16] 0 0
Ohio
Country [17] 0 0
United States of America
State/province [17] 0 0
Pennsylvania
Country [18] 0 0
United States of America
State/province [18] 0 0
Texas
Country [19] 0 0
United States of America
State/province [19] 0 0
Washington
Country [20] 0 0
Dominican Republic
State/province [20] 0 0
Santo Domingo
Country [21] 0 0
France
State/province [21] 0 0
Lyon
Country [22] 0 0
France
State/province [22] 0 0
Paris
Country [23] 0 0
Mexico
State/province [23] 0 0
Jalisco
Country [24] 0 0
Netherlands
State/province [24] 0 0
Utrecht
Country [25] 0 0
Spain
State/province [25] 0 0
Barcelona
Country [26] 0 0
Spain
State/province [26] 0 0
Madrid
Country [27] 0 0
Thailand
State/province [27] 0 0
Bangkok
Country [28] 0 0
Thailand
State/province [28] 0 0
Khon Kaen
Country [29] 0 0
United Kingdom
State/province [29] 0 0
Brighton
Country [30] 0 0
United Kingdom
State/province [30] 0 0
London
Country [31] 0 0
United Kingdom
State/province [31] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Gilead Study Director
Address 0 0
Gilead Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
18 months after study completion
Available to whom?
A secured external environment with username, password, and RSA code.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents



Results are available at https://clinicaltrials.gov/study/NCT01818596