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

September 15, 2017 updated by: St Stephens Aids Trust

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®)

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed 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

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
40

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Brighton, United Kingdom
        • Brighton & Sussex University Hospitals NHS Trust
      • London, United Kingdom
        • St. Mary's Hospital
      • London, United Kingdom
        • St. Stephen's Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Switch from Atripla to Eviplera
Drug: Eviplera
A single-pill fixed dose combination of tenofovir 245mg, emtricitabine 200mg and rilpivirine 25mg once daily for 24 weeks.
Other Names:
  • Rilpivirine, tenofovir, emtricitabine

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in neuropsychiatric and central nervous system (CNS) parameters after switching from Atripla to TDF/FTC/RPV at 4 weeks compared to baseline, as measured by the proportion of patients experiencing grade 2-4 neuropsychiatric and CNS toxicity
Time Frame: 4 Weeks compared to baseline
As defined by the ACTG Adverse event scale and collected by CNS questionnaire.
4 Weeks compared to baseline
Change in neuropsychiatric and central nervous system (CNS) parameters after switching from Atripla to TDF/FTC/RPV at 4 weeks compared to baseline, as measured by the median number of grade 2-4 neuropsychiatric and CNS toxicity
Time Frame: 4 Weeks compared to baseline
As defined by the ACTG adverse event scale and collected by CNS questionnaire.
4 Weeks compared to baseline
Change in neuropsychiatric and central nervous system (CNS) parameters after switching from Atripla to TDF/FTC/RPV at 4 weeks compared to baseline, as measured by the median CNS score.
Time Frame: 4 Weeks compared to baseline
Derived from the sum of toxicity of all grades collected in the CNS questionnaire.
4 Weeks compared to baseline
Change in neuropsychiatric and central nervous system (CNS) parameters after switching from Atripla to TDF/FTC/RPV at 4 weeks compared to baseline, as measured by the change in sleep score using the Pittsburgh Sleep Questionnaire.
Time Frame: 4 Weeks compared to baseline
4 Weeks compared to baseline

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in neuropsychiatric and central nervous system (CNS) parameters after switching from Atripla to TDF/FTC/RPV at 12 & 24 weeks compared to baseline, as measured by proportion of patients experiencing grade 2-4 neuropsychiatric and CNS toxicity.
Time Frame: 12 and 24 weeks compared to baseline
As defined by the ACTG adverse event scale and collected by CNS questionnaire.
12 and 24 weeks compared to baseline
Change in neuropsychiatric and central nervous system (CNS) parameters after switching from Atripla to TDF/FTC/RPV at 12 and 24 weeks compared to baseline, as measured by the median number of grade 2-4 neuropsychiatric and CNS toxicity.
Time Frame: 12 and 24 weeks compared to baseline
As defined by the ACTG adverse event scale and collected by CNS questionnaire.
12 and 24 weeks compared to baseline
Change in neuropsychiatric and central nervous system (CNS) parameters after switching from Atripla to TDF/FTC/RPV at 12 and 24 weeks compared to baseline, as measured by the median CNS score
Time Frame: 12 and 24 weeks compared to baseline
Median CNS score is derived from the sum of toxicity of all grades collected in the CNS questionnaire.
12 and 24 weeks compared to baseline
Change in neuropsychiatric and central nervous system (CNS) parameters after switching from Atripla to TDF/FTC/RPV at 12 and 24 weeks compared to baseline, as measured by change in sleep score using the Pittsburgh Sleep Questionnaire.
Time Frame: 12 and 24 weeks compared to baseline
12 and 24 weeks compared to baseline
Change in neuropsychiatric and CNS parameters as measured by the change in the Hospital Anxiety and Depression Scale (HADS) at 4, 12 and 24 weeks as compared with baseline.
Time Frame: 4, 12 and 24 weeks compared to baseline
4, 12 and 24 weeks compared to baseline
Proportion of patients with undetectable viral load (by local assay) at weeks 4, 12 and 24.
Time Frame: 4, 12 and 24 weeks compared to baseline
4, 12 and 24 weeks compared to baseline
Proportion of patients with viral load below 400 copies/mL at weeks 4, 12 and 24.
Time Frame: 4, 12 and 24 weeks compared to baseline
4, 12 and 24 weeks compared to baseline
Change in CD4+ count at week 12 and 24 compared to baseline.
Time Frame: 12 and 24 weeks compared to baseline
12 and 24 weeks compared to baseline
Proportion of patients with grade 2-4 laboratory adverse events (excluding lipids) and proportion of patients with grade 2-4 non-CNS adverse events at 4, 12 and 24 weeks compared with baseline.
Time Frame: 4, 12 and 24 weeks compared to baseline
4, 12 and 24 weeks compared to baseline
Change in mean fasting cholesterol (total, HDL, LDL and total:HDL ratio) and triglycerides after 4, 12 and 24 weeks compared with baseline.
Time Frame: 4, 12 and 24 weeks compared to baseline
4, 12 and 24 weeks compared to baseline
Change in quality of life (as assessed by EQ-5D questionnaire) at 4, 12 and 24 weeks compared with baseline.
Time Frame: 4, 12 and 24 weeks compared to baseline
4, 12 and 24 weeks compared to baseline
Change in neurocognitive function as determined by computerised neurocognitive assessment (no computerised cognitive testing at week 12)
Time Frame: 4, 12 and 24 weeks compared to baseline
4, 12 and 24 weeks compared to baseline
Change in neurocognitive function as determined by Instrumental Activities of Daily Life (IADL) questionnaire
Time Frame: 4, 12 and 24 weeks compared to baseline
4, 12 and 24 weeks compared to baseline
Change in adherence as measured by the adherence questionnaire: Medication Adherence Self-Report Inventory (M-MASRI) at 12 and 24 weeks compared with baseline.
Time Frame: 12 and 24 weeks compared to baseline
12 and 24 weeks compared to baseline
Change in cerebral MR-measurable imaging modalities at 24 weeks compared with baseline.
Time Frame: 24 weeks compared to baseline
24 weeks compared to baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
St Stephens Aids Trust

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Gilead Sciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 27, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 18, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 19, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 18, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 15, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SSAT058

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