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

St Stephens Aids Trust

Status and phase

Completed

Phase 4

Conditions

HIV

Treatments

Drug: Eviplera

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT02529059

SSAT058

Details and patient eligibility

About

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.

Full 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

Enrollment

40 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patient volunteers who meet all of the following criteria are eligible for this trial:

Is male or female aged 18 years or above
Has HIV-1 infection documented in their medical notes
Has signed the Informed Consent Form voluntarily
Is willing to comply with the protocol requirements
Has been on Atripla for at least 12 weeks before enrolment
Has an undetectable HIV-plasma viral load at screening by local assay (single re-test allowed)
Has a CD4 cell count at screening >50 cells/mm3
Has an estimated glomerular filtration rate (MDRD) >50 ml/min.
Has no significant CNS symptoms which may be attributable to EFV.
If female and of childbearing potential, is using effective birth control methods (for example, hormonal contraceptive, condom, abstinence, IUD, 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. 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 continue practising these birth control methods during the trial and until follow-up visit

Exclusion criteria

Patients meeting 1 or more of the following criteria cannot be selected:

Infected with HIV-2
Using any concomitant therapy disallowed as per SPC for the study drugs (e.g proton pump inhibitors )
Has acute viral hepatitis including, but not limited to, A, B, or C
Has chronic hepatitis B and/or C with AST and/or ALT >5 x ULN Note: Patients can enter trial with chronic HBV if HBV-DNA undetectable at screen (and no detectable result in last 6 months) and with chronic HCV if not expected to require treatment during the trial period.
Any investigational drug within 30 days prior to the trial drug administration
Has ever received rilpivirine in the past
Any clinical evidence of baseline resistance mutations, prior to commencing antiretroviral therapy.
Known allergy to lactose monohydrate, sunset yellow aluminium lake (E110), and patients with galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption
Severe hepatic impairment (defined as Child-Pugh-Turcotte (CPT) Score C).
If female, she is pregnant or breastfeeding
Screening blood result 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).
Any condition (including drug/alcohol abuse) or laboratory results which, in the investigator's opinion, interfere with assessments or completion of the trial.
If participating in the MR Imaging substudy, any contraindications to magnetic resonance scanning according to local radiology guidelines (to be assessed by MR Spectroscopy Imaging Department)