Renal Integrase Study

NCT02351908 | Completed Phase 4

• 1 other identifier: SSAT 066
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to observe the safety of Truvada® (TDF/FTC) in relation to its impact on kidney function combined with different Integrase Inhibitors (Dolutegravir, or Elvitegravir/Cobicistat or Raltegravir), when given to patients who are commencing treatment for HIV infection for the first time. All three combinations (Raltegravir + Truvada®, Dolutegravir + Truvada® and Stribild®, a single pill which contains Elvitegravir/Cobicistat/Truvada®) are currently recommended by the national guide-lines and used in standard clinical practice.

Conditions

HIV

Outcome Measures

Primary Outcomes (1)

• Change in retinol-binding protein/creatinine ratio (PCR) with each regimen over 24 weeks.

  The change in retinol-binding protein/creatinine ratio (PCR) with each regimen over 24 weeks (measured via nephelometric assay run on Siemens BNII nephelometer).

  24 weeks

Secondary Outcomes (8)

• Change in retinol-binding protein/creatinine ratio with each regimen over 12 and 48 weeks.

  48 weeks

• eGFR

  48 weeks

• Virologic response

  48 weeks

• Immunologic markers

  48 weeks

• Inflammatory markers

  48 weeks

Study Arms (3)

Arm 1

EXPERIMENTAL

Stribild® (Tenofovir Disoproxil Fumarate, Elvitegravir, Cobicistat150mg/150mg/200mg/245mg) tablet 1 once daily for 48 weeks

Drug: Stribild® (Tenofovir Disoproxil Fumarate, Elvitegravir, Cobicistat)

Arm 2

EXPERIMENTAL

Isentress® (Raltegravir 400 mg) 1 tablet twice a day + Truvada® (FTC \& Tenofovir) 1 tablet once a day for 48 weeks

Drug: Isentress® (Raltegravir 400 mg)1 tablet twice a day + Truvada® (FTC & Tenofovir) 1 tablet

Arm 3

EXPERIMENTAL

Tivicay® (Dolutegravir 50 mg) 1 tablet once a day + Truvada® (FTC \& Tenofovir) 1 tablet once a day for 48 weeks

Drug: Tivicay® (Dolutegravir 50 mg) 1 tablet once a day + Truvada® (FTC & Tenofovir)

Interventions

Stribild® (Tenofovir Disoproxil Fumarate, Elvitegravir, Cobicistat) DRUG

Arm 1

Isentress® (Raltegravir 400 mg)1 tablet twice a day + Truvada® (FTC & Tenofovir) 1 tablet DRUG

Arm 2

Tivicay® (Dolutegravir 50 mg) 1 tablet once a day + Truvada® (FTC & Tenofovir) DRUG

Arm 3

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Is male or female aged 18 years or above
• Has documented HIV-1 infection
• Has signed the Informed Consent Form voluntarily
• Is willing to comply with the protocol requirements, including dosing schedules of each regimen
• Has a HIV-plasma viral load at screening \>1000 copies/mL
• Has any CD4 cell count
• Has never been exposed to ART (other than via PEP or PREP, not associated with acquisition of HIV)
• Has an estimated glomerular filtration rate (MDRD method) \>60 ml/min
• Has no known resistance to TDF and FTC or to Integrase Inhibitors. HIV resistance test has to be dated no more than 1 year prior screening date. Only a RT/Pr gene resistance test is re-quired.
• If female and of childbearing potential, she is using effective birth control methods (as agreed by the investigator) and is willing to continue practising these birth control methods during the trial and for at least 30 days after the end of the trial (or after last intake of investigational ARVs); Dosing of the OCP may need to be adjusted if randomized to the Stribild® arm.
• Note: Women who are postmenopausal for least 2 years, women with total hysterectomy, and women who have a tubal ligation are considered of non-childbearing potential
• If a heterosexually active male, he is using effective birth control methods and is willing to con-tinue practising these birth control methods during the trial and until follow-up visit

You may not qualify if:

• Is infected with HIV-2
• Is using any concomitant therapy disallowed as per SPC for the study drugs
• Has a currently active AIDS defining illness (Category C conditions according to the CDC Classification System for HIV Infection-1993) with the following exceptions (must be discussed with the sponsor prior to enrolment):
• Stable cutaneous Kaposi's Sarcoma (no pulmonary or gastrointestinal involvement other than oral lesions) unlikely to require systemic therapy during the trial period
• CD4 count less than 200 cells/mm3 Note: Primary and secondary prophylaxis for an AIDS defining illness is allowed
• Has diabetes or any known or established renal disease or abnormality regardless of if stable
• Has presence at screening of proteinurea and or a urinary protein/creatinine ratio \>30
• Has untreated / not well controlled hypertension
• Has acute viral hepatitis including, but not limited to, A, B, or C
• Has chronic hepatitis B or chronic hepatitis C with AST and/or ALT \>5 x ULN Note: Subjects co-infected with chronic HCV (but not B) can enter the trial if clinically stable and not expected to require treatment during the trial period.
• Has received any investigational drug within 30 days prior to the trial drug administration
• No baseline resistance test to reverse transcriptase inhibitors available
• Clinically significant allergy or hypersensitivity or other contraindication to any trial medication or excipients
• If female, she is pregnant or breastfeeding
• Screening blood results with any grade 3 / 4 toxicity according to Division of AIDS (DAIDS) grading scale, except: asymptomatic grade 3 glucose, amylase or lipid elevation or asymptomatic grade 4 triglyceride elevation (re-test allowed).

Sponsors & Collaborators

• St Stephens Aids Trust: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

SSAT Clinical Research Facility

London, SW10 9NH, United Kingdom

Location

MeSH Terms

Interventions

Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Tenofovir; elvitegravir; Cobicistat; Raltegravir Potassium; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Racivir; dolutegravir

Intervention Hierarchy (Ancestors)

Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Organophosphonates; Organophosphorus Compounds; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations; Pyrrolidinones; Pyrrolidines

Study Officials

• Graeme Moyle, MD, MBBS, Dip GUN

  Chelsea and Westminster NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2015
• First Posted: January 30, 2015
• Study Start: March 1, 2015
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2017
• Last Updated: June 27, 2017

Record last verified: 2017-04

Locations

GB (1)