The primary objective of this study is:To evaluate the efficacy of a regimen containing elvitegravir/emtricitabine/tenofovir disoproxil fumarate/GS 9350 versus ritonavir-boosted atazanavir plus emtricitabine/tenofovir disoproxil fumarate in HIV 1…
ID
Source
Brief title
Condition
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Safety: Adverse events and clinical laboratory tests to evaluate the safety and
tolerability of the treatment regimens.
Efficacy: The primary efficacy endpoint is the proportion of subjects that
achieve HIV 1 RNA < 50 copies/mL at Week 48 as defined by the Food and Drug
Administration (FDA) snapshot analysis
Secondary outcome
The proportion of subjects with HIV 1 RNA * 50 copies/mL at Week 96, 144 and
192 as defined by the FDA snapshot analysis
The change from baseline in CD4+ cell count at Weeks 48, 96, 144 and 192.
Background summary
Approximately 33.2 million people are infected with HIV worldwide.
Standard-care for the treatment of HIV involves the use of a combination of
antiretroviral drugs to suppress viral replication and delay disease
progression. While combination ARV therapy has been largely successful in
reducing the morbidity and mortality associated with HIV disease, a significant
proportion of subjects eventually experience loss of virologic, immunologic or
clinical benefit from their current regimens.
Newer active ARV therapy regimens that offer reduced toxicity are needed for
treatment-naïve patients. In ongoing phase 2 and 3 clinical trials using
elvitegravir (EVG), an experimental inhibitor of HIV integrase, in combination
with other ARV drugs has been well tolerated and has not demonstrated an
increased incidence of the side effects with current combination ARV therapy.
The investigational pharmacoenhancer GS-9350 is devoid of anti-HIV activity,
may have less adverse biochemical effects relative to ritonavir, and can be
coformulated as a tablet with other ARV agents that require boosting. GS-9350
has been coformulated with EVG and the standard-of-care NRTI backbone FTC/TDF
into a FDC tablet. This FDC regimen may be an attractive option for
treatment-naïve patients with HIV-1 infection.
Study objective
The primary objective of this study is:
To evaluate the efficacy of a regimen containing
elvitegravir/emtricitabine/tenofovir disoproxil fumarate/GS 9350 versus
ritonavir-boosted atazanavir plus emtricitabine/tenofovir disoproxil fumarate
in HIV 1 infected, antiretroviral treatment-naïve adult subjects as determined
by the achievement of HIV 1 RNA < 50 copies/mL at Week 48
The secondary objectives of this study are:
To evaluate the efficacy, safety and tolerability of the two treatment regimens
through 96 weeks of treatment
To evaluate the durability of the efficacy, safety and tolerability results of
the two treatment regimens observed through 192 weeks of treatment
Study design
Randomized, double-blind, multicenter, active-controlled. Subjects will be
randomized in a 1:1 ratio to one of the two treatment arms. Randomization will
be stratified by HIV 1 RNA level (<= 100,000 copies/mL or >= 100,000 copies/mL)
at screening.
Intervention
Treatment arm 1: EVG/FTC/TDF/GS-9350 active + ritonavir 100 mg placebo +
atazanavir 300 mg placebo + Truvada® placebo.
Treatment arm 2: ritonavir 100 mg active + atazanavir 300 mg active +Truvada®
active + EVG/FTC/TDF/GS-9350 placebo.
Study burden and risks
In case of an average of 2 visites after week 96:
7 x comlete physical exam
12 x physical exam as needed
4 x ECG
1 x length
19 x weight
8 x fasten glucose- and lipid panel
EVG; ELVITEGRAVIR SIDE EFFECTS
Mild headache, mild diarrhea, mild vomiting, mild fatigue, mild nausea, mild
loss of appetite, dizziness, constipation, hypersensitivity, upper respiratory
tract infection, hypertension, and difficulty sleeping. No additional side
effects have been observed in clinical studies of EVG as an individual agent.
FTC; Emtriva® SIDE EFFECTS
(Emtricitabine)
Headache, diarrhea, nausea, rash, dizziness, changes in skin color, weakness,
difficulty sleeping, abnormal dreams, pain, vomiting, stomach pain, problems
with digestion, increased triglycerides (fatty acid), increased bilirubin in
the blood, increased glucose in the blood, allergic reaction, hives, adverse
effects on the function of the liver and pancreas, low white blood cell count,
increased creatine kinase in the blood, actic acidosis, and liver problems with
enlargement of the liver and fat in the liver, including fatal cases.
TDF; Viread® SIDE EFFECTS
(Tenofovir DF)
Diarrhea, nausea, vomiting, flatulence, dizziness, Immune Reconstitution
Syndrome with symptoms of infections and inflammation, allergic reactions,
weakness, abdominal pain, allergic reaction, pancreatitis, high levels of
amylase in the blood, shortness of breath, rash, abnormalities of tests that
measure hepatic function and hepatitis, lactic acidosis, liver problems with
enlargement of the liver and fat in the liver, including fatal cases, kidney
damage, and bone toxicity. Decreases in bone mineral density have been seen in
humans. The risk of bone fractures associated with these types of changes is
unknown.
GS-9350; SIDE EFFECTS
Upper extremity dyscoordination at the left side, difficulty concentrating,
somnolence, headache, abnormal dreams, acute hepatitis with increase in liver
enzyme levels, and mild decreases in estimated kidney function. No significant
changes in serum immunoglobulins (antibodies), ECG, thyroid hormone levels or
urine characteristics have been seen in clinical studies to date. In two
ongoing studies mild decreases in estimated kidney function were observed. A
follow-up study in healthy subjects showed that actual kidney function does not
change. No additional side effects have been observed in clinical studies of
GS-9350 as an individual agent.
Suicidal ideation and suicide attempt in patients with a pre-existing history
of depression or psychiatric illness has been identified as an uncommon adverse
reaction to EVG/COBI/FTC/TDF (occurred in more than or equal to 0.1% and less
than 1% of patients).
Lakeside Drive 333
Foster City CA 94404
US
Lakeside Drive 333
Foster City CA 94404
US
Listed location countries
Age
Inclusion criteria
Plasma HIV-1 RNA levels >= 5,000 copies/mL at screening
• No prior use of any approved or investigational antiretroviral drug for any length of time
• Screening genotype report provided by Gilead Sciences must show sensitivity to FTC,
TDF and ATV
• Adequate renal function: Estimated glomerular filtration rate >= 70 mL/min according to the Cockcroft-Gault formula.
• Hepatic transaminases (AST and ALT) <= 5 × upper limit of normal (ULN)
• Total bilirubin <= 1.5 mg/dL, or normal direct bilirubin
• 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)
• Age >= 18 years
• Life expectancy >= 1 year
Exclusion criteria
• A new AIDS-defining condition diagnosed within the 30 days prior to screening
• Subjects receiving drug treatment for Hepatitis C, or subjects who are anticipated to
receive treatment for Hepatitis C during the course of the study.
• Subjects experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, etc.)
• Have an implanted defibrillator or pacemaker
• Have an ECG PR interval >= 220 msec
• 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.
• Subjects receiving ongoing therapy with any of the medications as listed in the protocol v 15Mar2010 page 44.
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 | EUCTR2009--016758-4-NL |
| ClinicalTrials.gov | NCT01106586 |
| CCMO | NL31159.100.10 |