The primary objective of this study is:• To evaluate the non-inferiority of switching to a TAF Containing STR relative to maintaining TDF Containing Regimens in Virologically Suppressed HIV-1 positive subjects as determined by having HIV 1 RNA * 50…
ID
Source
Brief title
Condition
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Criteria for Evaluation:
Safety:
- Adverse events and clinical laboratory tests, including DXA and selected bone
and renal biomarkers to evaluate the safety and tolerability of the treatment
regimens.
- The efavirenz-related symptom assessment to evaluate the efavirenz-related
neuropsychiatric symptoms for subjects who took EFV/FTC/TDF as prior regimen.
Efficacy:
- The primary efficacy endpoint is the proportion of subjects that have HIV-1
RNA < 50 copies/mL at Week 48 as defined by the Food and Drug Administration
(FDA) snapshot analysis.
- The secondary efficacy endpoints are:
• The proportion of subjects achieving virologic response at Weeks 48 (HIV-1
RNA <20 copies/mL, snapshot analysis)
• The proportion of subjects achieving virologic response at Weeks 96 (HIV-1
RNA < 50 copies/mL and <20 copies/mL, snapshot analysis)
• The change in CD4 cell count at Weeks 48 and 96
PK:
- The pharmacokinetics of TAF and tenofovir will be assessed. The
pharmacokinetics of other study drugs and their metabolites may be explored.
Health-related Questionnaires:
- Health related questionnaires will be administered including the Medical
Outcome Study Short Form-36 (SF-36) and the EQ 5D-3L health questionnaire. The
SF-36 and EQ-5D-3L questionnaires will be administered at Baseline, Week 24 and
every 24 weeks thereafter, and at the ESDD visit.
Secondary outcome
See primary parameters/ outcome
Background summary
The treatment of HIV infection requires the combination of several medications
in order to decrease the amount of virus in the body, improve immune function
and delay the progression of the disease. This has generally required patients
to take a large number of pills each day, and many experience a loss of
effectiveness of their current medication regimen over time or unacceptable
side effects. Therefore, it is important to develop new drug regimens. In
addition, the combination of drugs into a single tablet reduces the number of
pills a patient has to take and makes it more convenient to stick to the
prescribed drug regimen.
The purpose of this study is to see if HIV-1 positive subjects currently taking
an antiretroviral (ARV) regimen consisting of EVG/COBI/FTC/TDF (E/C/F/TDF) STR,
EFV/FTC/TDF (Atripla®), cobicistat and atazanavir with FTC/TDF (Truvada®) or
ritonavir and atazanavir with FTC/TDF (Truvada®) can safely switch to E/C/F/TAF
STR without increasing the amount of HIV-1 in their blood. The safety and how
well these drug combinations are tolerated will be determined based on physical
exams, laboratory tests, bone scans and questions about any problems you might
experience during the study.
Study objective
The primary objective of this study is:
• To evaluate the non-inferiority of switching to a TAF Containing STR relative
to maintaining TDF Containing Regimens in Virologically Suppressed HIV-1
positive subjects as determined by having HIV 1 RNA * 50 copies/mL at Week 48
(FDA Snapshot Analysis).
The secondary objectives of this study are:
• To determine the safety of the two treatment arms as determined by the
percent change from baseline in hip and spine bone mineral density at Week 48
• To determine the safety of the two treatment arms as determined by the change
from baseline in serum creatinine at Week 48
• To evaluate the safety and tolerability of the two treatment arms through
Week 48
• To evaluate the durability of the efficacy, safety and tolerability of the
two treatment arms through Week 96
Study design
Een multi-centrum, gerandomiseerd, open label en actief gecontroleerd
onderzoek.. Proefpersonen zullen gerandomiseerd worden in een verhouding 2:1
naar een van de twee behandelingsgroepen.
A randomized, multicentre open label active controlled study. Subjects will be
randomized in a 2:1 ratio to one of the two treatment arms.
Intervention
Treatment group 1: Elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200
mg/tenofovir alafenamide 10 mg (E/C/F/TAF) STR administered orally QD
Treatment group 2: Current antiretroviral drug regimen consisting of E/C/F/TDF,
EFV/FTC/TDF, ATV/r + FTC/TDF, or ATV/co + FTC/TDF administered orally QD
Study burden and risks
For a complete overview of all study procedures Please refer to the protocol
and patientinformation leaflet. All risks are described in there.
Until November 2012, 112 HIV-positive subjects have been dosed with the
E/C/F/TAF combination pill as part of a Phase 2 study to evaluate the drug*s
safety and ability to suppress HIV viral load to undetectable levels
(efficacy). After 6 months of therapy, 87% of subjects had undetectable viral
loads (HIV-1 RNA < 50 copies/mL). Treatment was generally well tolerated as
most AEs were mild and not associated with treatment discontinuation. No new or
unexpected adverse events occurred. Subjects taking E/C/F/TAF had smaller
changes in markers of kidney function and bone mineral density than subjects on
a TDF-based regimen. The differences were statistically significant and may
have important clinical relevance for individual patients. The frequency and
type of adverse events and laboratory abnormalities was comparable to the
TDF-based regimen.
In addition, more than 100 HIV-negative subjects have been dosed with the
E/C/F/TAF combination pill as part of a Phase 1 study to evaluate the level of
each drug in the blood (pharmacokinetics). No deaths or serious side effects
occurred during the study. One subject discontinued from the study because of a
nonserious adverse event of increased creatinine phosphokinase (CPK) levels in
the blood that was assessed as related to study drug. The most frequently
reported side effect was constipation. Other side effects included nausea,
dizziness, headache, breast tenderness, and papular rash. No subject in any
treatment arm developed any clinically significant abnormalities on ECG
throughout the study.
Lakeside Drive 333
Foster City CA 94404
US
Lakeside Drive 333
Foster City CA 94404
US
Listed location countries
Age
Inclusion criteria
• Currently receiving antiretroviral therapy consisting of E/C/F/TDF, EFV/FTC/TDF, ATV/r + FTC/TDF, or ATV/co + FTC/TDF for >=6 consecutive months preceding the final visit in their earlier study
• Completion of the Week 144 visit in studies GS-US-236-0102, GS US 236 0103, GS US 216 0114, or completion of the Week 96 visit in study GS-US-264-0110 (only subjects on an efavirenz-based regimen), or completion of studies GS-US-236-0104, GS US 216 0105.
• Plasma HIV 1 RNA concentrations at undetectable levels for at least 6 consecutive months prior to the screening visit and have HIV RNA <50 copies/mL at the screening visit
• Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant)
• Estimated GFR >= 50 mL/min according to the Cockcroft Gault formula for creatinine clearance
• Hepatic transaminases (AST and ALT) <= 5 × upper limit of normal (ULN)
• Direct bilirubin <= 1.5 mg/dL x ULN
• Adequate hematologic function (absolute neutrophil count >= 1,000/mm3; platelets >=50,000/mm3; hemoglobin >= 8.5 g/dL)
• Serum amylase <= 5 × ULN (subjects with serum amylase > 5 × ULN will remain eligible if serum lipase is <= 5 × ULN)
• Females of childbearing potential must agree to utilize highly effective contraception methods or be non-heterosexually active or practice sexual abstinence from screening throughout the duration of study treatment and for 12 weeks following the last dose of study drug if receiving EFV/FTC/TDF regimen, and 30 days for those assigned to all other regimens.
* Female subjects 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.
* Female subjects who have stopped menstruating for >= 12 months but do not have documentation of ovarian hormonal failure must have a serum follicle stimulating hormone (FSH) level at screening within the post-menopausal range based on the Central Laboratory reference range.
• Male subjects must agree to utilize a highly effective method of contraception during heterosexual intercourse or be non-heterosexually active, or practice sexual abstinence from screening throughout the study period and for 12 weeks following discontinuation of investigational medicinal product if receiving EFV/FTC/TDF regimen, and 30 days for those assigned to all other regimens.
• Age >= 18 years
Exclusion criteria
• A new AIDS-defining condition diagnosed within the 30 days prior to screening
• Hepatitis B surface antigen (HBsAg) positive
• Hepatitis C antibody positive
• Subjects experiencing decompensated cirrhosis (e.g., 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 subject study compliance.
• A history of malignancy within the past 5 years (prior to screening) or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma. Subjects with cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Baseline and must not be anticipated to require systemic therapy during the study.
• Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Baseline.
• Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with the dosing requirements.
• Participation in any other clinical trial (including observational trials) without prior approval from the sponsor is prohibited while participating in this trial.
• Subjects receiving ongoing therapy with any of the medications mentioned in the table in the protocol, including drugs not to be used with EVG, COBI, FTC, TDF, ATV, RTV, EFV and TAF (refer to the individual agents Prescribing Information); or subjects with any known allergies to the excipients of E/C/F/TDF STR, E/C/F/TAF STR, EFV/FTC/TDF, ATV, COBI, RTV, or FTC/TDF.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2012-005114-20-NL |
| CCMO | NL43937.100.13 |