Elvitegravir/Cobicistat/Tenofovir DF/Emtricitabine With Darunavir Treatment Simplification Strategy

NCT ID: NCT02199613

Last Updated: 2017-11-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-10-31
• Study Completion Date: 2017-02-14

Brief Summary

The study aims to assess the safety and efficacy of darunavir 800mg plus the co-formulated elvitegravir/cobicistat/tenofovir disoproxil fumarate (DF)/emtricitabine (Stribild) tablet as a simplification strategy for the treatment of HIV infection in HIV-infected subjects who have had previous antiretroviral treatment experience with multiple-drug regimens.

We hypothesize that elvitegravir/cobicistat/tenofovir DF/emtricitabine with darunavir will offer a safe and efficacious treatment simplification strategy for HIV positive patients currently receiving multiple-drug regimens to control their HIV infection.

Detailed Description

Eligible, consenting subjects will be assessed at baseline and weeks 2, 12, 24, 36, and 48. Study medications will be dispensed at all visits except week 2, and all participants will commence taking open-label darunavir 800mg in conjunction with the co-formulated tenofovir DF/emtricitabine/cobicistat/elvitegravir (Stribild) tablet, both taken together once daily with food, following study procedures at baseline.

Assessments at the study visits will include:

1. Complete physical exam including height and weight at baseline; symptom-directed physical exam and weight at other visits

2. Adverse clinical events including serious adverse events (hospitalizations etc.) and medication changes at every visit.

3. HIV RNA every 4 weeks.

4. CD4 and CD8 absolute counts and % at all visits except week 2.

5. Platelet count, aspartate amino transferase (AST), creatinine, estimated glomerular filtration rate (eGFR), phosphorus, urinalysis, and urine albumin to creatinine ratio (UACR) at each visit.

6. Fasting lipids (total, HDL, and LDL cholesterol and triglycerides), apolipoprotein B, high-sensitivity C- reactive protein (hsCRP) at baseline, week 24, and week 48.

7. Pregnancy test for women of child-bearing potential (as defined above) at every visit except week 2. In addition, pregnancy tests will be performed monthly for women of child-bearing potential; between study visits these may be done at home.

8. A plasma sample (3 mL) will be collected and stored once at baseline for all subjects, and used for measurement of darunavir trough (pre-dose) concentration in subjects receiving darunavir in their pre-study regimen.

9. All subjects will take their study medication under observation in the clinic on Day 14, and plasma samples (3mL) for pharmacokinetic testing will be drawn immediately pre-dose and at 1, 2, 3, 4, 5, 6, and 8 hours post-dose. Subjects will return the following day before taking their Day 15 dose for a 24-hour post-dose sample.

10. Peripheral blood mononuclear cells (PBMCs) will be collected and stored at baseline for possible future study-related testing.

11. The following questionnaires will be completed by participants prior to other study procedures at baseline and at weeks 24 and 48: MOS-HIV quality of life questionnaire; HIVTSQ; ACTG treatment adherence questionnaire; and the medication adherence self-report inventory (MASRI).

Conditions

HIV Infection

Keywords

HIV; antiretroviral therapy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment simplification

Open-label darunavir 800mg in conjunction with the co-formulated tenofovir DF/FTC/cobicistat/elvitegravir (Stribild) tablet, both taken together once daily with food

Group Type: EXPERIMENTAL

Treatment simplification

Intervention Type: DRUG

Eligible, consenting subjects will start open-label darunavir 800mg plus the co-formulated tenofovir DF/FTC/cobicistat/elvitegravir (Stribild) tablet once daily with food, following the study procedures at the baseline visit. They will be assessed at weeks 2, 12, 24, 36, and 48 after starting the new regimen.

Interventions

Treatment simplification

Eligible, consenting subjects will start open-label darunavir 800mg plus the co-formulated tenofovir DF/FTC/cobicistat/elvitegravir (Stribild) tablet once daily with food, following the study procedures at the baseline visit. They will be assessed at weeks 2, 12, 24, 36, and 48 after starting the new regimen.

Intervention Type: DRUG

Other Intervention Names

Darunavir 800mg plus Stribild tablet once daily

Eligibility Criteria

Inclusion Criteria

• HIV positive adults > or = 19 years of age
• receiving stable therapy including one or two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), in conjunction with a once-daily protease inhibitor (PI) (atazanavir, lopinavir or darunavir) and twice daily raltegravir or once daily dolutegravir
• Virologic suppression for >6 months, defined as plasma viral load (VL) consistently < 200 copies/mL with no evidence of prior virologic rebound (VL > 1000 copies/mL) on the NRTI/PI/Raltegravir regimen, AND VL < 50 copies/mL at time of study screening
• Estimated glomerular filtration rate (eGFR) > o r= 70mL/min at screening

Exclusion Criteria

• Prior documented viral rebound > 1000 copies/mL on any raltegravir-containing regimen
• Evidence of resistance mutations compromising raltegravir or elvitegravir activity on prior genotypes.
• Evidence of clinically significant resistance to tenofovir on any previous genotype tests: K65R mutation, or 3 or more thymidine-analogue associated mutations (TAMS) compromising tenofovir activity
• Evidence of resistance mutations significantly compromising darunavir activity on any previous genotypic tests
• Current use of any nonnucleoside reverse transcriptase inhibitor (NNRTI)
• Pregnancy or breast-feeding
• Contraindications to tenofovir/FTC, elvitegravir, or cobicistat (e.g. previous significant toxicity, intolerance or drug interactions

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: collaborator

University of British Columbia

OTHER

Sponsor Role: lead

Responsible Party

Mark Hull

Clinical Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mark Hull, MD

Role: PRINCIPAL_INVESTIGATOR

University of British Columbia

Locations

St. Paul's Hospital Immunodeficiency Clinic

Vancouver, British Columbia, Canada

Countries

Canada

References

Harris M, Ganase B, Watson B, Harrigan PR, Montaner JSG, Hull MW. HIV treatment simplification to elvitegravir/cobicistat/emtricitabine/tenofovir disproxil fumarate (E/C/F/TDF) plus darunavir: a pharmacokinetic study. AIDS Res Ther. 2017 Nov 2;14(1):59. doi: 10.1186/s12981-017-0185-4.

Reference Type: DERIVED

PMID: 29096670 (View on PubMed)

Other Identifiers

H14-00490

Identifier Type: OTHER

Identifier Source: secondary_id

H14-00490

Identifier Type: -

Identifier Source: org_study_id