The primary objective of this study is:• To evaluate the efficacy of a single-tablet regimen (STR) containingelvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) versus a STRcontaining elvitegravir/cobicistat/emtricitabine/…
ID
Source
Brief title
Condition
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy endpoint is the proportion of subjects with HIV-1 RNA < 50
copies/mL
at Week 48 as defined by the FDA snapshot analysis.
Secondary outcome
The secondary endpoints include:
• The percent change from baseline in hip bone mineral density (BMD) at Week 48
• The change from baseline in serum creatinine at Week 48
Background summary
There is more necessity for long-term therapy for patients with HIV-1 infection
as more patients are diagnosed on a younger age. Renal and bone health, in both
of these contexts, are increasingly important.
E/C/F/TDF is approved for use in the America for the treatment of HIV-1
infection. The new IP E/C/F/TAF might possibly improve the efficacy and
long-term safety profile of E/C/F/TDF. Moreover, it might have less adverse
events (amongst others less nephrotoxicity and less decreased bone
mineral density).
Study objective
The primary objective of this study is:
• To evaluate the efficacy of a single-tablet regimen (STR) containing
elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) versus
a STR
containing elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate
(E/C/F/TDF) in HIV-1 positive, 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 determine the safety of the two treatment regimens as determined by the
percent
change from baseline in hip bone mineral density at Week 48
• To determine the safety of the two treatment regimens as determined by the
change from
baseline in serum creatinine at Week 48
• To evaluate the safety and tolerability of the two treatment regimens through
Week 48
• To evaluate the efficacy, durability, safety and tolerability of the two
treatment regimens
through Week 96
Study design
Randomized, double-blind, multicenter, active-controlled study to
evaluate the safety and efficacy of a regimen containing
elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide
(E/C/F/TAF administered as a STR) versus
elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate
(E/C/F/TDF administered as a STR) in HIV-1 positive,
antiretroviral treatment-naïve adult subjects.
Intervention
Treatment Arm 1: STR of elvitegravir 150 mg/cobicistat
150 mg/emtricitabine 200 mg/ tenofovir alafenamide 10 mg
(E/C/F/TAF) QD + Placebo to match STR of elvitegravir
150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir
disoproxil fumarate 300 mg (E/C/F/TDF) QD (n = 420)
Treatment Arm 2: STR of elvitegravir 150 mg/cobicistat
150 mg/emtricitabine 200 mg/ tenofovir disoproxil fumarate
300 mg (E/C/F/TDF) QD + Placebo to match STR of elvitegravir
150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir
alafenamide 10 mg (E/C/F/TAF) QD (n = 420).
Study burden and risks
Please refer for a complete overview to the 'study procedures table' in the
protocol.
Patients will have to come more often to the hospital for this research. All
research medications will have to be taken once a day, every day at the same
time, during dinner.
A questionnaire will be completed (EQ-5D)
The research contains a farmacokinetic part also. As part of this research at
different time points during the research the concentration HIV-1 in the blood
(the viral loading) and the concentrations of the research medications will be
measured.
Adverse events of E/C/F/TAF:
As of 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 Adverse Events (AEs) were mild and not associated with stopping the study
treatment. 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 treatment 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 creatine 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
(electrocardiogram) 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
• Plasma HIV-1 RNA levels >= 1,000 copies/mL at screening
• No prior use of any approved or investigational antiretroviral drug for any length of time,
except the use for PREP (pre-exposure prophylaxis) or PEP (post-exposure prophylaxis) up to 6 months prior to screening.
• Screening genotype report must show sensitivity to EVG, FTC and TDF
• 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
Exclusion criteria
• A new AIDS-defining condition diagnosed within the 30 days prior to screening (refer to
Appendix 5)
• Hepatitis B surface antigen (HBsAGg) 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 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 following medications in the table
below, including drugs not to be used with EVG, COBI, FTC, TDF, and TAF (refer to
the individual agents Prescribing Information); or subjects with any known allergies to
the excipients of E/C/F/TDF or E/C/F/TAF single-tablet regimen tablets.
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 | EUCTR2012-004458-27-NL |
| ClinicalTrials.gov | NCT01780506 |
| CCMO | NL42921.100.13 |