Primary: Antiviral efficacy of dolutagravir in combination with Kivexa (abacavir en lamivudine) after 48 weeks of treatment in comparison with Atripla (tenofovir, emtricitabine and efavirenz). Secondary: Antiviral efficacy after 96 and 144 weeks,…
ID
Source
Brief title
Condition
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
HIV1-RNA (<50 copies/ml) week 48.
Secondary outcome
E.g. the time to viral suppression (<50 copies/mL), the proportion of subjects
with plasma HIV-1 RNA <50 copies/mL at Week 96 and 144, the change from
baseline in CD4 at week 48, the proportion of subjects with HIV-1 RNA >=1,000
copies/mL at or after 16 and before 24 weeks, or >= 200 copies/mL at 24 weeks,
adverse events, quality of life.
Background summary
Integrase inhibitors (INIs) are a new class of antiretroviral drugs designed to
block the action of the integrase viral enzyme, which catalyzes several key
steps in the HIV life cycle and is responsible for insertion of the viral
genome into the DNA of the host cell. The first INI for the treatment of HIV-1
infected subjects was raltegravir.
In the STARTMRK study, raltegravir demonstrated excellent antiviral activity as
first line treatment and was shown to be non-inferior to an
efavirenz-containing (Sustiva) standard of care regimen in the STARTMRK trial.
The time to achieve viral suppression was shorter for subjects on raltegravir
than on efavirenz. There were fewer drug-related adverse events reported in the
raltegravir group and fewer subjects randomized to raltegravir discontinued
from the study due to adverse events, highlighting the promise for better
long-term tolerability with INI-based therapy. However, RAL requires twice
daily dosing, which is a disadvantage when compared to multiple once daily
options, and is currently not available in a fixed dose combination (FDC)
regimen. In addition, RAL has a low genetic barrier to resistance, given that
RAL-associated mutations readily develop in the setting of virologic failure.
Therefore, the development of new INIs with different resistance profiles, the
potential for higher barrier to resistance, and improved dosing administration
is desirable.
GSK1349572 (dolutagravir) is a next-generation INI that may deliver these
attributes. Its 14-hour plasma half-life supports once daily dosing. It
possesses potent antiviral activity. The compound has no significant CYP P450
enzyme inhibition, and thus has low drug-drug interaction liabilities.
This present study is designed to establish the safety and efficacy of
GSK1349572 50 mg once daily in adults infected with HIV-1 who are ART-naïve.
Protocol amendement 04-05: treatment arms from Week 96 to Week 144 in order to
collect long term efficacy and safety data for the use of GSK1349572.
Study objective
Primary: Antiviral efficacy of dolutagravir in combination with Kivexa
(abacavir en lamivudine) after 48 weeks of treatment in comparison with Atripla
(tenofovir, emtricitabine and efavirenz). Secondary: Antiviral efficacy after
96 and 144 weeks, safety and tolerability, resistance development, incidence of
HIV-associated conditions, gender-, race-, and/or HIV-1 subtype on response to
GSK1349572, quality of life.
Study design
Multicenter randomized double blind phase III non-inferiority parallel group
study and open-label extension week 96-144.
Randomization (1:1) to treatment with:
2. Dolutagravir 50 mg plus Kivexa once daily.
2. Atripla once daily.
Treatment duration 144 weeks.
Subjects randomized to receive GSK1349572 plus ABC/3TC therapy and who
successfully complete 96 weeks of treatment will be given the opportunity to
continue to receive this treatment as part of the study until either GSK1349572
is locally approved and commercially available, they no longer derive clinical
benefit, they meet a protocol-defined reason for discontinuation, or the
development of the compound is terminated.
Patients from arm 2 will be treated with Atripla until week 144 (1st 96 weeks
in a double blind fashion).
Interim-analysis planned after last subject completed 48 weeks of treatment.
IDMC.
Approx 800 patients.
Intervention
Treatment with GSK1349572 plus Kivexa or Atripla.
Study burden and risks
Risk: Adverse effects of study medication.
Burden: 15 visits in 96 weeks. Thereafter every12 week until week 144 (all
patients) or until one of the the stopcriteria defined in the section study
design is met (dolutagravir group).Visit duration 1-4 uur.
Blood tests 15x approx. 20-35 ml/visit (total 400 ml in the 1st 96 weeks),
pregnancy test (if relevant) nearly every visit, ECG 2x. Questionnaire (EQ 5D,
GHO Symptom Distress Module) 4-5x.
Huis ter Heideweg 62
Zeist 3705 LZ
NL
Huis ter Heideweg 62
Zeist 3705 LZ
NL
Listed location countries
Age
Inclusion criteria
• HIV-1 infected subjects >=18 years of age.
• HIV-1 infection as documented by HIV-1 RNA >400 c/mL.
• No prior antiretroviral therapy.
• HLA-B*5701 negative.
• Safe contraception for women of childbearing potential.
Exclusion criteria
• Breastfeeding, pregnancy.
• Any evidence of an active CDC Category C disease [CDC, 1993], except cutaneous Kaposi*s sarcoma not requiring systemic therapy or historic or current CD4+ cell count <200 cells/mm3 are not exclusionary.
• History of malignancy within the past 5 years or ongoing malignancy other than the usual exceptions.
• Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening.
• Treatment with any of the following agents within 28 days of Screening: radiation, cytotoxic chemotherapeutic agents, immunomodulators.
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 |
|---|---|
| Other | clinicaltrials.gov, regsitratienummer n.n.b. |
| EudraCT | EUCTR2010-020983-39-NL |
| CCMO | NL34518.101.10 |