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

NCT ID: NCT02529059

Last Updated: 2017-09-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-11-30

Study Completion Date

2017-05-31

Brief Summary

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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.

Detailed Description

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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

Conditions

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HIV

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Switch from Atripla to Eviplera

Group Type EXPERIMENTAL

Eviplera

Intervention Type DRUG

A single-pill fixed dose combination of tenofovir 245mg, emtricitabine 200mg and rilpivirine 25mg once daily for 24 weeks.

Interventions

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Eviplera

A single-pill fixed dose combination of tenofovir 245mg, emtricitabine 200mg and rilpivirine 25mg once daily for 24 weeks.

Intervention Type DRUG

Other Intervention Names

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Rilpivirine, tenofovir, emtricitabine

Eligibility Criteria

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Inclusion Criteria

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

1. Is male or female aged 18 years or above
2. Has HIV-1 infection documented in their medical notes
3. Has signed the Informed Consent Form voluntarily
4. Is willing to comply with the protocol requirements
5. Has been on Atripla for at least 12 weeks before enrolment
6. Has an undetectable HIV-plasma viral load at screening by local assay (single re-test allowed)
7. Has a CD4 cell count at screening \>50 cells/mm3
8. Has an estimated glomerular filtration rate (MDRD) \>50 ml/min.
9. Has no significant CNS symptoms which may be attributable to EFV.
10. 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
11. 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:

1. Infected with HIV-2
2. Using any concomitant therapy disallowed as per SPC for the study drugs (e.g proton pump inhibitors )
3. Has acute viral hepatitis including, but not limited to, A, B, or C
4. 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.
5. Any investigational drug within 30 days prior to the trial drug administration
6. Has ever received rilpivirine in the past
7. Any clinical evidence of baseline resistance mutations, prior to commencing antiretroviral therapy.
8. Known allergy to lactose monohydrate, sunset yellow aluminium lake (E110), and patients with galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption
9. Severe hepatic impairment (defined as Child-Pugh-Turcotte (CPT) Score C).
10. If female, she is pregnant or breastfeeding
11. 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).
12. Any condition (including drug/alcohol abuse) or laboratory results which, in the investigator's opinion, interfere with assessments or completion of the trial.
13. 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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role collaborator

St Stephens Aids Trust

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mark Nelson

Role: PRINCIPAL_INVESTIGATOR

St Stephen's AIDs Trust

Locations

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Brighton & Sussex University Hospitals Nhs Trust

Brighton, , United Kingdom

Site Status

St. Mary's Hospital

London, , United Kingdom

Site Status

St. Stephen's Centre

London, , United Kingdom

Site Status

Countries

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United Kingdom

Other Identifiers

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SSAT058

Identifier Type: -

Identifier Source: org_study_id