Study to Evaluate the Safety Tolerability and Acceptability of Long Acting Injections of the Human Immunodeficiency Virus (HIV) Integrase Inhibitor, GSK1265744, in HIV Uninfected Men (ECLAIR)
Condition: Infection, Human Immunodeficiency Virus
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections; Immunologic Deficiency Syndromes
Intervention: 744 Tablet; 744 LA Injection; Placebo Tablet; Placebo Injection
Intervention description: White to almost white oval shaped film coated 30 mg tablets for oral administration; Sterile white to slightly coloured suspension containing 200 mg/mL of 744 as free acid for administration by intramuscular (IM) injection; Microcrystalline cellulose, Opadry film-coating, white OY-S-28876; Sterile saline 0.9% Sodium Chloride Injection
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 127.0
Sex: Male
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Pre-Exposure Prophylaxis; HIV integrase; Intramuscular Injection; GSK1265744

Summary:

      This study is a Phase IIa, randomized, multi-site, two-arm, double-blinded study to evaluate
      the safety, tolerability, and acceptability of GSK1265744 long acting injectable formulation
      (744 LA) in adult male subjects. To evaluate the safety and tolerability of the injectable
      agent, 744 LA (800 milligrams (mg) dose administered at three time points at 12 week
      intervals) through Week 41 in HIV-uninfected men. Eligible participants will be randomized in
      a 5:1 ratio to receive 744 LA or matching placebo. Participants will receive daily oral 744
      (30 mg tablets) or matching placebo for 4 weeks during the Oral Phase of the study, followed
      by a one week washout period. Following safety lab assessments from the Oral Phase,
      participants will enter the Injection Phase and receive Intramuscular (IM) injections of 744
      LA or placebo at three time points at 12 week intervals. IM injections will consist of 800 mg
      of 744 or a matching control
    

Eligibility criteria:

        Inclusion Criteria:

          -  Non-reactive HIV test at screening or enrollment.

          -  Males 18 to 65 years old at the time of signing the informed consent.

          -  At risk of acquiring HIV, defined as having at least one casual sex partner in the
             past 24 months.

          -  Healthy as determined by a responsible and experienced physician, based on a medical
             evaluation including medical history, physical examination, laboratory tests and
             cardiac monitoring at the time of screening.

          -  If participating in sexual activity with a female of child-bearing potential, men must
             agree to use condoms. Subjects who are sexual partners of females with child bearing
             potential must also agree to practice an acceptable method of contraception for the
             duration of the study, such as double barrier (male condom/spermicide, male
             condom/diaphragm) or female partner use of hormonal contraception, intrauterine device
             (IUD) or other method with published data showing that the lowest expected failure
             rate for that is less than 1% per year. All subjects participating in the study must
             be counseled on safer sexual practices including the use of effective barrier methods
             to minimize risk of HIV transmission.

          -  Capable of giving written informed consent, which includes compliance with the
             requirements and restrictions listed in the consent form.

          -  Willing to undergo all required study procedures

        Exclusion Criteria:

          -  One or more reactive HIV test results at screening or enrollment, even if HIV
             infection is not confirmed. Negative HIV Ribonucleic acid (RNA) must also be
             documented at screening.

          -  Assessed by the Investigator of Record or designee as being at "high risk" for HIV
             infection. This may include one or more of the following:

        The negative partner in an HIV serodiscordant couple Men who exchange sex for goods or
        money Men who have engaged in unprotected receptive anal intercourse within the past 6
        months Men who have had greater than 3 sexual partners within the past 3 months Men who
        have had a sexually transmitted disease within the past 6 months Any other behavior
        assessed by the investigator as "high risk"

          -  Co-enrollment in any other HIV interventional research study (provided by self-report
             or other available documentation) or prior enrollment and receipt of the active arm
             (i.e., NOT a placebo) of a HIV vaccine trial (provided by available documentation).

          -  Use of antiretroviral (ARV) therapy (e.g., for Post exposure prophylaxis (PEP) or Pre
             exposure prophylaxis (PrEP) in the past 30 days, five half-lives, or twice the
             duration of the biological effect of the applied treatment (whichever is longer) prior
             to study enrollment.

          -  Current or chronic history of liver disease, or known hepatic or biliary abnormalities
             (with the exception of Gilbert's syndrome or asymptomatic gallstones).

          -  History of drug or alcohol consumption that in the opinion of the Principal
             Investigator will interfere with study participation.

          -  History of sensitivity to any of the study medications, or components thereof or a
             history of drug or other allergy that, in the opinion of the investigator or Medical
             Monitor, contraindicates their participation.

          -  Any of the following laboratory values during the screening period. Positive Hepatitis
             C antibody result Positive Hepatitis B surface antigen (HBsAg) Hemoglobin less than 11
             gram (g)/deci liter (dL) Absolute neutrophil count less than 750 cells/mm^3 Platelet
             count less than or equal to 100,000/mm^3 Presence of a coagulopathy as defined by an
             INR greater than 1.5 or a PTT greater than 45sec Calculated creatinine clearance less
             than 70 mL/minute using the Cockcroft-Gault equation A single repeat test is allowed
             during the Screening period to verify a result, with the exception of HIV tests.

          -  Subjects with an alanine aminotransferase (ALT), alkaline phosphatase (ALP) or
             bilirubin greater than or equal to1.5xULN (isolated bilirubin greater than 1.5xULN is
             acceptable if bilirubin is fractionated and direct bilirubin less than 35%).

          -  History of the following cardiac diseases: myocardial infarction, congestive heart
             failure, documented hypertrophic cardiomyopathy, sustained ventricular tachycardia.

          -  The subject's systolic blood pressure is outside the range of 90-160mmHg, or diastolic
             blood pressure is outside the range of 45-90mmHg or heart rate is outside the range of
             45-100 beats per minute (bpm).

          -  Exclusion criteria for screening (ECG (a single repeat is allowed for eligibility
             determination) for Male Subjects:

        Heart rate (A heart rate from 100 to 110 bpm can be rechecked within 30 minutes to verify
        eligibility)-less than 45 and greater than 100 bpm.

        QRS duration-greater than 120 msec. QTc interval (B or F)-greater than 450 msec. Evidence
        of previous myocardial infarction (does not include ST segment changes associated with
        repolarization).

        Any conduction abnormality (including but not specific to left or right complete bundle
        branch block, AV block [2nd degree or higher], Wolf Parkinson White [WPW] syndrome).

        Sinus Pauses greater than 3 seconds. Any significant arrhythmia which, in the opinion of
        the principal investigator and medical monitor, will interfere with the safety for the
        individual subject.

        Non-sustained or sustained ventricular tachycardia (greater than or equal to 3 consecutive
        ventricular ectopic beats).

          -  Ongoing intravenous drug use - episodic use or any use in the past 90 days is
             exclusionary (as assessed by the study investigator).

          -  The subject has a tattoo or other dermatological condition overlying the gluteus
             region which may interfere with interpretation of ISRs.

          -  Use of high dose aspirin or any other anticoagulant or antiplatelet medication that
             would interfere with the ability to receive intramuscular injections.

          -  Active skin disease or disorder (i.e., infection, inflammation, dermatitis, eczema,
             drug rash, psoriasis, urticaria). Mild cases of localized acne or folliculitis or
             other mild skin condition may not be exclusionary at the discretion of the
             Investigator of Record or Medical Monitor).