| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Human Immunodeficiency Virus Type-1 (HIV-1) |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10068341 |
| E.1.2 | Term | HIV-1 infection |
| E.1.2 | System Organ Class | 100000004862 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate antiviral efficacy of GSK3640254 relative to DTG, each given in combination with 2 NRTIs, enabling the selection of an optimal dose for GSK3640254 |
|
| E.2.2 | Secondary objectives of the trial |
-To evaluate antiviral efficacy in the Randomised Phase of GSK3640254 relative to DTG, each given in combination with 2 NRTIs at Week 48
-To evaluate antiviral efficacy in the Non-Randomised Phase of GSK3640254 optimal dose given in combination with DTG relative to the reference arm (DTG given in combination with 2 NRTIs) at Week 96
-To evaluate safety and tolerability in the Randomised Phase of GSK3640254 relative to DTG, each given in combination with 2 NRTIs at Weeks 24 and 48
-To evaluate safety and tolerability in the Non- Randomised Phase of GSK3640254 optimal dose given in combination with DTG relative to the reference arm (DTG given in combination with 2 NRTIs) at Week 96
-To assess the development of viral resistance in the Randomised Phase to GSK3640254 and 2 NRTI backbone in participants experiencing virologic failure at Weeks 24 and 48.
A complete list of Secondary Objectives can be found on p10 of the protocol |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Optional Stomach Substudy
To explore the monitoring of potential gastric toxicity in the stomach of HIV-1 infected
participants, a substudy will explore the potential relationship (if any) between Serum
Biomarkers and the occurrence of any findings on EGD on biopsy
Specifically, this will be accomplished by participants voluntarily electing to take part in
a Stomach substudy (e.g., signing a separate additional informed consent form [ICF]
agreeing to undergo the procedure at the GI facility). The Stomach substudy will seek to
recruit 7 participants from each of the 4 treatment arms, 28 participants in total. |
|
| E.3 | Principal inclusion criteria |
-Participants must be 18 years of age inclusive, at the time of signing the informed consent.
-Treatment-naïve, defined as no ARVs (in combination or monotherapy) received after the diagnosis of HIV-1 infection (e.g., use of PreP meets inclusion);
-Documented HIV infection and Screening plasma HIV-1 RNA ≥1000 copies/mL;
-Screening CD4+ T-cell count ≥350 cells/mm3;
-Body weight ≥50.0 kg (110 lbs.) for men and ≥45.0 kg (99 lbs) for women and body mass index (BMI) > 18.5 kg/m2.
-Male and female
*NOTE: There are no contraceptive requirements for male participants.
a. Female Participants
Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical
studies.
-A female is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
-Is a woman of non-childbearing potential (WONCBP) as defined in Section 10.4 of the protocol, Contraceptive and Barrier Guidance;
OR
-Is a WOCBP (as defined in Section 10.4 of the protocol) and using an acceptable contraceptive method as described in Section 10.4.2 during the study intervention period (at a minimum until after the last dose of study intervention). The investigator should evaluate the potential for
contraceptive method failure (e.g., noncompliance, recently initiated in relationship to the first dose of study intervention.
-If a hormonal method is selected, the female participant is required to be clinically stable on it for at least one month prior to starting
treatment in the study.
-A WOCBP must have a negative highly sensitive serum pregnancy test 42 days before the first dose of study intervention. See Section 8.2.5
Pregnancy Testing.
-Additional requirements for pregnancy testing during and after study intervention are located in Section 8.2.5.
-The Investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a
woman with an early undetected pregnancy.
-Capable of giving signed informed consent as described in Section 10.1.3 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
-For participants enrolled in France: a participant will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category. |
|
| E.4 | Principal exclusion criteria |
-Any evidence of an active Centers for Disease Control and Prevention (CDC) Stage
3 disease [CDC, 2014], except cutaneous Kaposi’s sarcoma not requiring systemic
therapy;
-Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma,
or resected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal or
penile intraepithelial neoplasia;
Note: Other localized malignancies require agreement between the investigator
and the ViiV Medical Monitor for inclusion.
-Presence of primary HIV-1 infection, evidenced by acute retroviral syndrome (e.g.,
fever, malaise, fatigue, etc.) and/or evidence of recent (within 3 months) documented
viremia without antibody production and/or evidence of recent (within 3 months)
documented seroconversion;
-Known history of liver cirrhosis with or without viral hepatitis co-infection;
-Unstable liver disease (as defined by any of the following: presence of ascites,
encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or
persistent jaundice or cirrhosis), known biliary abnormalities (with the exception of
Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver
disease per investigator assessment)
-History of ongoing or clinically relevant hepatitis within the previous 6 months;
-History of sensitivity to any of the study medications or their components or drugs of
their class, or a history of drug or other allergy that, in the opinion of the Investigator
or Medical Monitor, contraindicates their participation;
-Any history of significant underlying psychiatric disorder, in the opinion of the
Investigator or ViiV Medical Monitor, including but not limited to schizophrenia,
bipolar disorder with or without psychotic symptoms, other psychotic disorders, or
schizotypal (personality) disorder;
-Any history of major depressive disorder with or without suicidal features, or
anxiety disorders, that required medical intervention (pharmacologic or not) such as
hospitalization or other inpatient treatment and/or chronic (>6 months) outpatient
treatment;
Note: Participants with other conditions such as adjustment disorder or dysthymia
that have required shorter term medical therapy (<6 months) without inpatient
treatment and are currently well-controlled clinically or resolved may be
considered for entry after discussion and agreement with the ViiV Medical
Monitor.
-Any pre-existing physical or other psychiatric condition (including alcohol or drug
abuse), which, in the opinion of the Investigator or ViiV Medical Monitor (with or
without psychiatric evaluation), could interfere with the participant’s ability to
comply with the dosing schedule and protocol evaluations or which might
compromise the safety of the participant;
-A pre-existing condition, in the opinion of the Investigator or ViiV Medical Monitor,
that could interfere with normal gastrointestinal anatomy or motility (e.g.,
gastroesophageal reflux disease [GERD], gastric ulcers, gastritis, inflammatory
bowel disease), hepatic and/or renal function, or with the absorption, metabolism,
and/or excretion of the study drugs or render the participant unable to take oral study
treatment;
-Myocardial infarction in the past 3 months;
-Familial or personal history of long QT syndrome;
-Medical history, current or historical, of significant cardiac arrhythmias or ECG
findings which, in the opinion of the Investigator or ViiV Medical Monitor, will
interfere with the safety of the participant;
Note: Examples of ECG findings include symptomatic bradycardia, non-sustained
or sustained atrial arrhythmias, non-sustained ventricular tachycardia (VT) or
sustained VT, second degree atrioventricular block (AVB) Mobitz Type II, or
third degree AVB.
-Active Treatment for a viral infection other than HIV-1, such as Hepatitis B, with an
agent that is active against HIV-1 (were known to be infected with HIV-1 after
treatment for Hepatitis B was completed);
-Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening;
-Treatment with any of the following agents within 28 days of Screening: radiation
therapy, cytotoxic chemotherapeutic agents, any systemic immune suppressant;
-Participants receiving any protocol-prohibited medication and who are unwilling or
unable to switch to an alternate medication;
-Participants who are unwilling to stop any medications as required by the local lab
test for H. pylori.
-Participants who require concomitant medications known to be associated with a
prolonged QTc (see list from https://www.crediblemeds.org).
-Exposure to an experimental drug or experimental vaccine within either 28 days
prior to the first dose of study treatment;
Note: Consult with the Medical Monitor if clarification is needed.
For a full list of exclusion criteria refer to the study protocol Section 5.2 |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Proportion of participants with plasma HIV-1 RNA <50 copies/mL at Week 24 using the
FDA snapshot algorithm |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
-Proportion of participants with plasma HIV-1 RNA <50 copies/mL at Weeks 48 and 96
using the FDA snapshot algorithm
-Absolute values and changes from baseline in HIV-1 RNA through Weeks 24, 48, and 96
-Absolute values and changes from baseline in CD4+ cell counts through Weeks 24, 48,
and 96
-Frequency of SAEs, Deaths and AEs leading to Discontinuation through Weeks 24, 48, and 96
-Incidence and severity of AEs through Weeks 24, 48 and 96
-AEs in GI, Psych/CNS through Weeks 24, 48 and 96
-Changes in genotypic and/or phenotypic profiles of virus compared to baseline
through Weeks 24, 48, and 96
-The steady-state plasma PK parameters of GSK3640254 will be assessed based on
Intensive and/or Sparse PK sampling through Weeks 24 and 48 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| Partially blind, dose-range |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 32 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Canada |
| Russian Federation |
| South Africa |
| United States |
| France |
| Germany |
| Italy |
| Portugal |
| Spain |
| Switzerland |
| Argentina |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
For study status purposes, a participant is considered to be complete if they attend the last
on treatment visit at the end of study for participants in the GSK2640254 arm, and at
Week 144 (for participants in the DTG reference arm). The Follow-Up visit is not
required for successful completion of the study.
The study will be completed when either the development of GSK3640254 is
discontinued or until GSK3640254 is locally approved and commercially available
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 7 |
| E.8.9.1 | In the Member State concerned months | 3 |
| E.8.9.1 | In the Member State concerned days | 14 |
| E.8.9.2 | In all countries concerned by the trial years | 7 |
| E.8.9.2 | In all countries concerned by the trial months | 3 |
| E.8.9.2 | In all countries concerned by the trial days | 14 |
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