Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00007284

Trial Description

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Title

A Phase IIb Study Evaluating a Long-Acting Intramuscular Regimen of GSK1265744 Plus TMC278 For The Maintenance of Virologic Suppression Following an Induction of Virologic Suppression on an Oral Regimen of GSK1265744 Plus Abacavir/Lamivudine in HIV-1 Infected, Antiretroviral Therapy-Naive Adult Subjects

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

This study is a Phase IIb, randomized, multicentre, parallel group, open-label, study having
an overall objective to evaluate the antiviral activity, tolerability, and safety of two
intramuscular (IM) dosing regimens of GSK744 LA plus TMC278 LA, relative to GSK744 30
milligram (mg) plus Abacavir/Lamivudine (ABC/3TC) given orally once daily (QD), in HIV-1
infected antiretroviral-naïve subjects. GSK744 is the oral formulation of GSK1265744, GSK744
LA is the long acting injectable formulation of GSK1265744 and TMC278 LA is the long acting
injectable formulation of TMC278.

The study will consist of three parts: an Induction Period, Maintenance Period and Extension
Period. There is also a Long-Term Follow Up Period for subjects who withdraw from the study
and have received at least one dose of GSK744 LA and / or TMC278 LA. In the Induction
Period, eligible subjects will receive a combination of an oral regimen of 30 mg of GSK744
and 600/300 mg of ABC/3TC, once daily for 20 weeks. In the Maintenance Period, eligible
subjects will be randomized 2:2:1 at Day 1 to receive an IM regimen of GSK744 LA 400 mg +
TMC278 LA 600 mg every 4 weeks for 96 weeks (Q4W), an IM regimen of GSK744 LA 600 mg +
TMC278 LA 900 mg every 8 weeks for 96 weeks (Q8W), or to continue on the oral Induction
Period regimen of GSK744 30 mg + ABC/3TC once daily for 96 weeks (or 104 weeks if continuing
on to the Extension Period). The Extension Period will allow for a collection of longer term
efficacy and safety and tolerability data from subjects receiving GSK744 LA and TMC278 LA.

The study will involve sufficient subjects at screening in order to ensure a total of
approximately 265 subjects at the beginning of the Induction Period and approximately 225
subjects randomized into the Maintenance Period.

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Brief Summary in Scientific Language

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Organizational Data

  •   DRKS00007284
  •   2015/08/06
  •   2014/04/17
  •   no
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Secondary IDs

  •   NCT02120352  (ClinicalTrials.gov)
  •   200056  (ViiV Healthcare)
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Health Condition or Problem studied

  •   Infection, Human Immunodeficiency Virus
  •   Z21 -  Asymptomatic human immunodeficiency virus [HIV] infection status
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Interventions/Observational Groups

  •   Drug: GSK744
  •   Drug: GSK744 LA
  •   Drug: TMC278 LA
  •   Drug: ABC/3TC
  •   Drug: RPV
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Open (masking not used)
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  •   Active control
  •   Treatment
  •   Parallel
  •   II
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Primary Outcome

- The proportion of subjects with HIV-1 Ribonucleic acid (RNA) <50 copies/millilitre (c/mL) at Maintenance Week 32; time frame: Week 32; The endpoint at Week 32 is based on the ITT-Maintenance Exposed population using the MSDF (Missing, Switch or Discontinuation = Failure) (Snapshot) algorithm.
- The proportion of subjects with protocol defined virologic failures over time; time frame: Up to Week 96/Withdrawal; Virologic failure is defined as any of the following: Non-response as indicated by a less than a 1.0 log10 copies/mL decrease in plasma HIV-1 RNA after 4 weeks of starting the Induction Period (subsequently confirmed, unless the plasma HIV-1 RNA is <400 c/mL). Rebound as indicated by two consecutive plasma HIV-1 RNA levels >=200 c/mL after prior suppression to < 200 c/mL. Rebound as indicated by two consecutive plasma HIV-1 RNA that are > 0.5 log10 c/mL increase in plasma HIV-1 RNA from the nadir value on study, where the lowest HIV-1 RNA value is >=200 c/mL.
- Incidence and severity of adverse events (AEs) over time; time frame: Up to Week 96/Withdrawal; An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product
- Incidence and severity of laboratory abnormalities over time; time frame: Up to Week 96/Withdrawal; Laboratory tests will include haematology, clinical chemistry, and urinalysis parameters.

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Secondary Outcome

- Proportion of subjects with plasma HIV-1 RNA <200 c/mL and <50 c/mL, for oral dose of GSK744 30 mg plus ABC/3TC; time frame: Up to Week 96/Withdrawal; The antiviral activity of GSK744 30 mg plus ABC/3TC orally once daily will be evaluated, through the Induction and Maintenance Periods.
- Absolute values and change from Baseline in plasma HIV-1 RNA, for oral dose of GSK744 30 mg plus ABC/3TC; time frame: Baseline to Week 96; The antiviral activity of GSK744 30 mg plus ABC/3TC oral once daily, by measuring the absolute values and change from Baseline in plasma HIV-1 RNA will be evaluated, through the Induction and Maintenance Periods.
- Absolute values and changes from Baseline in CD4+ cell counts, for oral dose of GSK744 30 mg plus ABC/3TC; time frame: Baseline to Week 96; The antiviral activity of GSK744 30 mg plus ABC/3TC orally once daily will be evaluated, by measuring the absolute values and change from Baseline in CD4+ cell counts, through the Induction and Maintenance Periods.CD4+ lymphocyte count will be obtained by flow cytometry
- Incidence of disease progression for oral dose of GSK744 30 mg plus ABC/3TC; time frame: Up to Week 96/Withdrawal; The incidence will be evaluated using indicators of clinical disease progression including HIV-associated conditions, acquired immunodeficiency syndrome [AIDS] and death after administration of oral dose of GSK744 30 mg plus ABC/3TC
- Incidence and severity of AEs over time, for oral dose of GSK744 30 mg plus ABC/3TC; time frame: Up to Week 96/Withdrawal; An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
- The incidence and severity of laboratory abnormalities over time, for oral dose of GSK744 30 mg plus ABC/3TC; time frame: Up to Week 96/Withdrawal; Laboratory tests will include haematology, clinical chemistry, and urinalysis parameters.
- Absolute values and changes in laboratory parameters over time, for oral dose of GSK744 30 mg plus ABC/3TC; time frame: Up to Week 96/Withdrawal; Laboratory tests will include haematology, clinical chemistry, and urinalysis parameters.
- Proportion of subjects with plasma HIV-1 RNA <200 c/mL and <50 c/mL over time, for GSK744 LA 400 mg IM plus TMC278 LA 600 mg IM every 4 weeks and GSK744 LA 600 mg IM plus TMC278 LA 900 mg every 8 weeks, relative to GSK744 plus ABC/3TC orally once daily; time frame: Up to Week 96/Withdrawal; The efficacy, tolerability, and safety will be evaluated through Week 96 of the Maintenance Period. Plasma HIV-1 RNA will be measured by ABBOTT REALTIME™ HIV-1 Assay with LLOD of 40 c/mL. Additional exploratory methods may be used in some cases. ABBOTT REALTIME is a trademark owned by Abbott Laboratories.
- Proportion of subjects with protocol defined virologic failures over time, for GSK744 LA 400 mg IM plus TMC278 LA 600 mg IM every 4 weeks and GSK744 LA 600 mg IM plus TMC278 LA 900 mg every 8 weeks, relative to GSK744 30 mg plus ABC/3TC orally once daily; time frame: Up to Week 96/Withdrawal; Virologic failure is defined as any of the following: Non-response indicated by a less than a 1.0 log10 copies/mL decrease in plasma HIV-1 RNA after 4 weeks of starting the Induction Period (subsequently confirmed, unless the plasma HIV-1 RNA is <400 c/mL). Rebound as indicated by two consecutive plasma HIV-1 RNA levels >=200 c/mL after prior suppression to < 200 c/mL. Rebound as indicated by two consecutive plasma HIV-1 RNA that are > 0.5 log10 c/mL increase in plasma HIV-1 RNA from the nadir value on study, where the lowest HIV-1 RNA value is >=200 c/mL.
- The absolute values and change from Baseline in plasma HIV-1 RNA, for GSK744 LA 400 mg IM plus TMC278 LA 600 mg IM every 4 weeks and GSK744 LA 600 mg IM plus TMC278 LA 900 mg every 8 weeks, relative to GSK744 30 mg plus ABC/3TC orally once daily; time frame: Up to Week 96/Withdrawal; Plasma HIV-1 RNA will be measured by Abbott Real time HIV-1 Assay with LLOD of 40 c/mL. Additional exploratory methods may be used in some cases.
- Absolute values and changes from Baseline in CD4+ cell counts, for GSK744 LA 400 mg IM plus TMC278 LA 600 mg IM every 4 weeks and GSK744 LA 600 mg IM plus TMC278 LA 900 mg every 8 weeks, relative to GSK744 30 mg plus ABC/3TC orally once daily; time frame: Up to Week 96/Withdrawal; CD4+ lymphocyte count will be obtained by flow cytometry
- The incidence of disease progression for GSK744 LA 400 mg IM plus TMC278 LA 600 mg IM every 4 weeks and GSK744 LA 600 mg IM plus TMC278 LA 900 mg every 8 weeks, relative to GSK744 30 mg plus ABC/3TC orally once daily; time frame: Up to Week 96/Withdrawal; The incidence will be evaluated using indicators of clinical disease progression including HIV-associated conditions, AIDS and death.
- Incidence of disease progression through Week 96 of the Maintenance Period.; time frame: Up to Week 96/Withdrawal; The incidence will be evaluated using indicators of clinical disease progression including HIV-associated conditions, AIDS and death
- Incidence and severity of AEs, for GSK744 LA 400 mg IM plus TMC278 LA 600 mg IM every 4 weeks and GSK744 LA 600 mg IM plus TMC278 LA 900 mg every 8 weeks, relative to GSK744 30 mg plus ABC/3TC orally once daily; time frame: Up to Week 96/Withdrawal; An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product
- Incidence and severity of laboratory abnormalities, for GSK744 LA 400 mg IM plus TMC278 LA 600 mg IM every 4 weeks and GSK744 LA 600 mg IM plus TMC278 LA 900 mg every 8 weeks, relative to GSK744 30 mg plus ABC/3TC orally once daily; time frame: Up to Week 96/Withdrawal; Laboratory tests will include haematology, clinical chemistry, ECGs, and urinalysis parameters
- Absolute values and changes in laboratory parameters, for GSK744 LA 400 mg IM plus TMC278 LA 600 mg IM every 4 weeks and GSK744 LA 600 mg IM plus TMC278 LA 900 mg every 8 weeks, relative to GSK744 30 mg plus ABC/3TC orally once daily; time frame: Up to Week 96/Withdrawal; Laboratory tests will include haematology, clinical chemistry, ECGs, and urinalysis parameters
- Plasma pharmacokinetic (PK) parameters for GSK744 LA and TMC278 LA during the Maintenance Period; time frame: Up to Week 96/Withdrawal; PK parameters included (C trough and concentrations post dose [~Cmax])
- Plasma GSK744 and RPV trough concentrations; time frame: Up to Week 96/Withdrawal; To determine when steady state is achieved for each GSK744 LA and TMC278 LA regimen Concentrations of GSK1265744 and TMC278 will be determined in plasma samples.
- PK-pharmacodynamic (PD) assessment for GSK744 LA and TMC278 LA; time frame: Up to Week 48; The PK-PD relationship will be explored between plasma PK parameters and plasma HIV-1 RNA, CD4+ cell counts and/or occurrence of AEs through Week 48 of the Maintenance Period.
- Incidence of treatment emergent genotypic and phenotypic resistance to GSK1265744, TMC278, and other on-study Antiretroviral Therapy (ART).; time frame: Up to Week 96/Withdrawal; The development of viral resistance will be assessed in subjects experiencing protocol defined virologic failure.
- The proportion of subjects with plasma HIV-1 RNA <50 c/mL over time.; time frame: Up to Week 96/Withdrawal; The effect of various demographic Baseline characteristics and adherence on virologic response of GSK1265744 and TMC278 will be explored. Plasma HIV-1 RNA will be measured by Abbott Real time HIV-1 Assay with LLOD of 40 c/mL. Additional exploratory methods may be used in some cases.
- To evaluate the treatment satisfaction for subjects on the long-acting injectable regimens with those on the oral regimen using the HIV Treatment Satisfaction Questionnaire Status (HIVTSQ(s)), through Week 96 of the Maintenance Period.; time frame: Up to Week 96/Withdrawal; The HIV Treatment Satisfaction Questionnaire (HIVTSQ) will assess change in treatment satisfaction over time (in the same subjects) and compare current satisfaction with previous treatment satisfaction, from an earlier time point. HIVTSQ(s) is the status version of the questionnaire.
- To evaluate the change in treatment satisfaction for subjects using the HIV Treatment Satisfaction Questionnaire Change (HIVTSQ[c]) through Week 32 of the Maintenance Period.; time frame: Up to Week 32; HIVTSQ will assess change in treatment satisfaction over time (in the same subjects) and compare current satisfaction with previous treatment satisfaction, from an earlier time point. HIVTSQ(c) is the revised changed version.
- To evaluate medication adherence over time using the HIV Medication Questionnaire (HIVMQ).; time frame: Up to Week 96/Withdrawal; HIVMQ is used to assess medication adherence as reported by the subjects.

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Countries of Recruitment

  •   United States
  •   Canada
  •   France
  •   Germany
  •   Spain
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Locations of Recruitment

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Recruitment

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  •   2014/04/30
  •   265
  •   Multicenter trial
  •   International
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

- Subjects screened for this study must be HIV-1 infected and >=18 years of age.

- A female subject is eligible to enter and participate in the study if she: is of
non-child-bearing potential defined as either post-menopausal (12 months of
spontaneous amenorrhea and >=45 years of age) or physically incapable of becoming
pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy or;
is of child-bearing potential with a negative pregnancy test at both Screening and
first day of the Induction Period and agrees to use one of the following methods of
contraception to avoid pregnancy 2 weeks prior to administration of IP, throughout
the study, and for at least 2 weeks after discontinuation of all oral study
medications and for at least 52 weeks after discontinuation of GSK744 LA and TMC278
LA: Complete abstinence from intercourse (where this is the subject's preferred and
usual lifestyle); double barrier method (male condom/spermicide, male
condom/diaphragm, diaphragm/spermicide); approved hormonal contraception; any
intrauterine device (IUD) with published data showing that the expected failure rate
is <1% per year; male partner sterilization prior to the female subject's entry into
the study, and this male is the sole partner for that subject; any other method with
published data showing that the lowest expected failure rate is <1% per year; any
contraception method must be used consistently and in accordance with the approved
product label. All subjects participating in the study must follow safer sexual
practices including the use of effective barrier methods (e.g. male
condom/spermicide) to minimize risk of HIV transmission.

- HIV-1 infection as documented by Screening plasma HIV-1 RNA>=1000 c/mL.

- CD4+ cell count >=200 cells/mm^3 (or higher as local guidelines dictate).

- ART-naive defined as having no more than 10 days of prior therapy with any
antiretroviral agent following a diagnosis of HIV-1 infection. Any previous exposure
to an HIV integrase inhibitor or non-nucleoside reverse transcriptase inhibitor will
be exclusionary.

- French subjects: In France, a subject will be eligible for inclusion in this study
only if either affiliated to or a beneficiary of a social security category.

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Exclusion Criteria

- Women who are breastfeeding.

- Any evidence at screening of an active Center for Disease and Prevention Control
(CDC) Category C disease, except cutaneous Kaposi's sarcoma not requiring systemic
therapy.

- Subjects with known moderate to severe hepatic impairment.

- Any pre-existing physical or mental condition (including substance abuse disorder)
which, in the opinion of the Investigator, may interfere with the subject's ability
to comply with the dosing schedule and/or protocol evaluations or which may
compromise the safety of the subject.

- Subject who, in the investigator's judgment, poses a significant suicide risk.
Recent history of suicidal behavior and/or suicidal ideation may be considered as
evidence of serious suicide risk.

- The subject has a tattoo or other dermatological condition overlying the gluteus
region which may interfere with interpretation of injection site reactions.

- History of ongoing or clinically relevant hepatitis within the previous 6 months,
including chronic Hepatitis B virus (HBV) infection (HBsAg positive). Asymptomatic
individuals with chronic hepatitis C virus (HCV) infection will not be excluded,
however Investigators must carefully assess if therapy specific for HCV infection is
required; subjects who are anticipated to require such therapy during the randomized
portion of the study must be excluded.

- History of liver cirrhosis with or without hepatitis viral co-infection.

- Ongoing or clinically relevant pancreatitis.

- History of the following cardiac diseases: myocardial infarction, congestive heart
failure, documented hypertrophic cardiomyopathy, sustained ventricular tachycardia.

- Personal or known family history of prolonged QT syndrome.

- Any condition which, in the opinion of the Investigator, may interfere with the
absorption, distribution, metabolism or excretion of the drug or render the subject
unable to receive study medication.

- History or presence of allergy or intolerance to the study drugs or their components
or drugs of their class. In addition, if heparin is used during PK sampling,
subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia
must not be enrolled.

- Current or anticipated need for chronic anti-coagulation.

- Any evidence of primary resistance based on the presence of any major
resistance-associated mutation in the Screening result or, if known, any historical
resistance test result.

- Any verified Grade 4 laboratory abnormality.

- Any acute laboratory abnormality at Screening, which, in the opinion of the
Investigator, would preclude the subject's participation in the study of an
investigational compound.

- Subject has estimated creatinine clearance <50 mL/min via Cockcroft-Gault method.

- Alanine aminotransferase (ALT) >=5 times Upper limit of normal (ULN). Subjects with
ALT >2xULN but <5xULN may participate in the study, if in the opinion of the
Investigator and GlaxoSmithKline (GSK) medical monitor the lab abnormality will not
interfere with the study procedures or compromise subject safety.

- Alanine aminotransferase (ALT) >=3xULN and bilirubin >=1.5xULN (with >35% direct
bilirubin).

- Any clinically significant finding on screening or Baseline electrocardiograph (ECG),
specifically: Heart rate <45 and >100 beats per minute (bpm) (Males) and <50 and >100
bpm (Females) (100 to 110 bpm can be rechecked within 30 minutes to verify
eligibility), QRS duration >120 milliseconds (msec), QTc interval (B or F) >450 msec;
non-sustained (>=3 consecutive beats) or sustained ventricular tachycardia; sinus
pauses >2.5 seconds; 2nd degree (Type II) or higher atrio-ventricular (AV) block;
evidence of WPW (Wolff- Parkinson-White) syndrome (ventricular pre-excitation);
pathologic Q waves defined as Q wave >40msec OR depth >0.4 mV; any significant
arrhythmia (either on ECG or by history) which, in the opinion of the Investigator
and GSK medical monitor, will interfere with the safety for the individual subject.

- Subjects who are human leukocyte antigen (HLA)-B*5701 positive and unable to use an
alternative nucleoside reverse transcriptase inhibitor (NRTI) backbone (subjects who
are HLA-B*5701 positive may be enrolled if they use an alternative NRTI backbone that
does not contain abacavir).

- Exposure to an experimental drug and/or experimental vaccine within 28 days or 5
half-lives of the test agent, or twice the duration of the biological effect of the
test agent, whichever is longer, prior to the first dose of IP.

- Treatment with any of the following agents within 28 days of Screening; radiation
therapy, cytotoxic chemotherapeutic agents, tuberculosis therapy and Immunomodulators
that alter immune responses (such as systemic corticosteroids, interleukins, or
interferons)

- Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening.

- Treatment with any agent, except recognized ART as allowed above, with documented
activity against HIV-1 within 28 days of the first dose of IP.

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Addresses

  • start of 1:1-Block address primary-sponsor
    • ViiV Healthcare
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    • Janssen Pharmaceuticals
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    • GlaxoSmithKline
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  • start of 1:1-Block address scientific-contact
    • ViiV Healthcare
    • GSK Clinical Trials 
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  • start of 1:1-Block address public-contact
    • ViiV Healthcare
    • GSK Clinical Trials 
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Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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Status

  •   Recruiting complete, follow-up continuing
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Trial Publications, Results and other Documents

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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   1
  •   2014/11/05
* This entry means the parameter is not applicable or has not been set.