Status:

TERMINATED

Dose-finding Study of GSK2248761 in Antiretroviral Therapy-Naive Subjects (SIGNET)

Lead Sponsor:

ViiV Healthcare

Collaborating Sponsors:

GlaxoSmithKline

Conditions:

Infection, Human Immunodeficiency Virus

Eligibility:

All Genders

18+ years

Phase:

PHASE2

Brief Summary

This 96 week, Phase 2b study in 150 HIV-1 infected antiretroviral (ART) naive adult subjects consists of a dose-ranging evaluation of GSK2248761 at blinded doses of 100 mg and 200 mg once daily with a...

Detailed Description

Study SGN113404 is a phase 2b randomized, partially blinded, multicenter, parallel group, dose-ranging study. The study will be conducted in approximately 150 HIV-1 infected ART naïve subjects. The ba...

Eligibility Criteria

Inclusion

  • HIV-1 infected adults greater than or equal to 18 years of age. A female is eligible to enter and participate in the study if she is (1) Non-childbearing potential, (2) Child-bearing potential, with a negative pregnancy test at screen and Day 1 and agrees to use protocol-specified methods of birth control while on study
  • HIV-1 infection with a screening plasma HIV-1 RNA greater than or equal to 1000 copies/mL
  • CD4+ cell count greater than or equal to 200 cells/mm3
  • Antiretroviral-naive

Exclusion

  • 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
  • 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 take oral medication
  • Women who are currently breastfeeding
  • Any evidence of an active Centers for Disease and Prevention Control (CDC) Category C disease \[CDC,1993\], except cutaneous Kaposi's sarcoma not requiring systemic therapy
  • 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
  • History or presence of allergy or intolerance to the study drugs or their components, or a history of drug or other allergy that, in the opinion of the Principal Investigator, contraindicates their participation. In addition, if heparin is used during PK sampling, subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia should not be enrolled
  • Evidence of viral resistance to any antiviral drug indicative of primary transmitted resistance in a screening or historical resistance test result
  • 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. Any verified Grade 4 laboratory abnormality at screening would exclude a subject from study participation unless the Investigator can provide a compelling explanation for the laboratory result(s) and has the assent of the Medical Monitor
  • Any of the following laboratory values at screening: (1) Creatinine clearance \<50 mL/min via Cockroft-Gault method, (2) Alanine aminotransferase (ALT) greater than or equal to 5 times upper limits of normal (ULN). Subjects with ALT \> 2x ULN but \<5xULN may participate in the study, if in the opinion of the Investigator and GSK Medical Monitor the lab abnormality will not interfere with the study procedures or compromise subject safety, (3) Alanine aminotransferase (ALT) greater than or equal to 3xULN and bilirubin greater than or equal to 1.5xULN (with \>35% direct bilirubin)
  • Any clinically significant finding on screening ECG, specifically (a single repeat is allowed to determine eligibility): (1) Heart rate \<45 and \>100 beats per minute (bpm) (males); \<50 and \>100 bpm (females). Note: A heart rate from 100 to 110 bpm can be rechecked within 30 minutes to verify eligibility, (2) QRS duration \> 120 msec, (3) QTc interval \> 450 msec (4) Non-sustained (greater than or equal to 3 consecutive beats) or sustained ventricular tachycardia, (5) Sinus pauses \> 2.5 seconds, (6) 2nd degree (Type II) or higher AV (Atrioventricular) block, (7) Evidence of WPW (Wolff- Parkinson-White) syndrome (ventricular preexcitation), (8) Pathologic Q waves (defined as Q wave \> 40 msec OR depth \>0.4 mV (9) Any other abnormality which in the opinion of the Investigator would interfere with the safety of the subject
  • Treatment with any of the following agents within 28 days prior to screening, or has an anticipated need for these agents during the study (1) Radiation therapy or cytotoxic chemotherapeutic agents, (2) Immunomodulators (such as systemic corticosteroids, interleukins, or interferons) Note: Subjects using short-term (\<7 day) steroid tapers and inhaled corticosteroids are eligible for enrollment (3) Any non-protocol-specified agent with documented activity against HIV 1 in vitro
  • Treatment with an HIV-1 immunotherapeutic vaccine within 90 days prior to screening
  • Receipt of an experimental drug and/or vaccine within 28 days or 5 half-lives, or twice the duration of the biological effect of the experimental drug or vaccine, whichever is longer, prior to screening
  • Immunization within 28 days prior to first dose of IP

Key Trial Info

Start Date :

November 18 2010

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

July 4 2011

Estimated Enrollment :

23 Patients enrolled

Trial Details

Trial ID

NCT01231555

Start Date

November 18 2010

End Date

July 4 2011

Last Update

November 17 2017

Active Locations (12)

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Page 1 of 3 (12 locations)

1

GSK Investigational Site

Levallois-Perret, France, 92300

2

GSK Investigational Site

Montpellier, France, 34295

3

GSK Investigational Site

Nice, France, 06202

4

GSK Investigational Site

Paris, France, 75018