SSAT058: Atripla to Eviplera Switch in Patients Without Central Nervous System Symptoms

HIV Clinical Trial

Official title: A Phase IV, Open-label, Multi Centre Pilot Study to Assess Changes in Cerebral Function Parameters in Patients Without Perceived Central Nervous System (CNS) Symptoms When Switched From a Fixed Dose Combination of Tenofovir/Emtricitabine/Efavirenz (Atripla®) to a Fixed Dose Combination of Tenofovir/Emtricitabine/Rilpivirine (Eviplera®)

Status Completed

Clinical Trial Summary

This study aims to investigate whether substitution of Efavirenz (EFV) as the Tenofovir/Emtricitabine/Efavirenz (TDF/FTC/EFV) fixed-dose combination (FDC) Atripla, with Rilpivirine as the tenofovir/emtricitabine/rilpivirine (TDF/FTC/RPV) fixed-dose combination (FDC) Eviplera, leads to resolution of covert Central Nervous System (CNS) toxicity associated with EFV, continued virological suppression and immunological reconstitution and whether this is associated with an improvement in quality of life, sleep, anxiety/depression and neurocognitive function; the impact of switch on adherence will also be investigated.

Clinical Trial Description

Protocol Summary

Study Title: SSAT 058 - A phase IV, open-label, multi centre pilot study to assess the prevalence of objective neurocognitive abnormality in patients without perceived Central Nervous System (CNS) symptoms on tenofovir/emtricitabine/efavirenz Atripla® and the effect of switching to a fixed dose combination of tenofovir/emtricitabine/rilpivirine (Eviplera®).

Proposed Sponsor: St Stephen's AIDS Trust

Chief Investigator: Dr Mark Nelson

Name of Investigational Product: Eviplera®

Name of Active Ingredients: Rilpivirine, tenofovir, emtricitabine

Name of Non Investigational Medicinal Product : NA

Name of Active Ingredients: NA

Phase of Study: Phase IV

Objectives: The objectives of this study are:

Primary objectives

• To describe prevalence pattern, in patients without self-perceived CNS symptoms related to tenofovir/emtricitabine/efavirenz, of the following parameters assessed at baseline:

• Objective neurocognitive function testing.

• Self-reported central nervous system symptoms by questionnaire

• Reported Sleep quality Secondary objectives

• change in measured neurocognitive parameters from baseline to week 4 and 24

• change in sleep scores from baseline to week 4 and 24

• change in symptoms related to CNS toxicity from baseline over 24 weeks

• change in magnetic resonance imaging (MRI) and spectroscopy of brain between baseline and week 24.

• the rate of maintained virological suppression at <50 copies/ml at each visit over 24 weeks

• changes in fasting lipids from baseline over 24 weeks

• change in reported adherence from baseline and to week 24 in:

• adherence

• Quality of life

• Reported anxiety and depression

Study Design: Multi-centre, open-label, single pilot study of 24 weeks. Study visits will take place at screening, baseline (within 36 days of screening visit), weeks 4, 12 and 24.

Substudy of 10 volunteers - MRI scan at baseline and week 24

Indication: HIV-1-infection

Methodology:

• Neurocognitive function testing measured by computerised tasks.

• CNS symptoms and sleep quality determined by questionnaire.

• Changes in CNS metabolites by 1H-MR spectroscopy imaging.

Planned Sample Size: 40 (across 4 centres)

Summary of Eligibility Criteria: HIV-infected individuals on Atripla with a viral load < 50 copies/mL and a CD4 count > 50 cells/mm3.

Number of Study Centres: 4

Duration of Treatment: 24 weeks

Dose and Route of Administration: A single-pill fixed dose combination of tenofovir 245mg, emtricitabine 200mg and rilpivirine 25mg once daily.

Primary Endpoint: Summary of overall prevalence and categorised descriptions of the following measures will be determined at baseline:

• Neurocognitive function scores calculated as composite scores and individual domains.

• Reported CNS symptoms assessed using questionnaire based on Summary of Product Characteristics (SPC) will be scored for severity and reported as both individual and composite scores.

• Sleep Quality assessed by questionnaire at baseline.

Secondary Endpoint:

• change in measured neurocognitive parameters from baseline to week 4 and 24

• change in sleep scores from baseline to week 4 and 24

• change in symptoms related to CNS toxicity from baseline over 24 weeks

• Change in magnetic resonance imaging and spectroscopy of brain between baseline and week 24.

• the rate of maintained virological suppression at <50 copies/ml at each visit over 24 weeks

• changes in fasting lipids from baseline over 24 weeks

• change in reported adherence from baseline and to week 24 in:

• adherence

• Quality of life

• Reported anxiety and depression ;

Related Conditions & MeSH terms

• HIV

• NCT number: NCT02529059
• Study type: Interventional
• Source: St Stephens Aids Trust
• Status: Completed
• Phase: Phase 4
• Start date: November 2015
• Completion date: May 2017