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)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT02076178
First received: February 27, 2014
Last updated: August 7, 2014
Last verified: August 2014
  Purpose

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


Condition Intervention Phase
Infection, Human Immunodeficiency Virus
Drug: 744 Tablet
Drug: 744 LA Injection
Drug: Placebo Tablet
Drug: Placebo Injection
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase IIa Study to Evaluate the Safety, Tolerability and Acceptability of Long Acting Injections of the HIV Integrase Inhibitor, GSK1265744, in HIV Uninfected Men (ECLAIR)

Resource links provided by NLM:


Further study details as provided by ViiV Healthcare:

Primary Outcome Measures:
  • Safety and Tolerability as assessed by adverse events [ Time Frame: Up to Week 41 (Final visit) ] [ Designated as safety issue: No ]
    To evaluate the safety and tolerability of the injectable agent, 744 LA (800 mg dose administered at three time points at 12 week intervals) through Week 41 in HIV-uninfected men as assessed by adverse events

  • Safety and Tolerability as assessed by concurrent medication required [ Time Frame: Up to Week 41 (Final visit) ] [ Designated as safety issue: No ]
    To evaluate the safety and tolerability of the injectable agent, 744 LA (800 mg dose administered at three time points at 12 week intervals) through Week 41 in HIV-uninfected men as assessed by concurrent medication required

  • Safety and Tolerability as assessed by clinical laboratory tests [ Time Frame: Up to Week 41 ] [ Designated as safety issue: No ]
    To evaluate the safety and tolerability of the injectable agent, 744 LA (800 mg dose administered at three time points at 12 week intervals) through Week 41 in HIV-uninfected men as assessed by clinical laboratory tests (Hematology/Chemistry testing and Urinalysis)

  • Safety and Tolerability as assessed by Electrocardiogram (ECG) [ Time Frame: Up to Week 41 ] [ Designated as safety issue: No ]
    To evaluate the safety and tolerability of the injectable agent, 744 LA (800 mg dose administered at three time points at 12 week intervals) through Week 41 in HIV-uninfected men as assessed by ECG

  • Safety and Tolerability as assessed by vital signs assessments [ Time Frame: Up to Week 41 ] [ Designated as safety issue: No ]
    To evaluate the safety and tolerability of the injectable agent, 744 LA (800 mg dose administered at three time points at 12 week intervals) through Week 41 in HIV-uninfected men as assessed by vital signs assessments

  • Safety and Tolerability as assessed by injection site reactions (ISRs) [ Time Frame: Up to Week 41 (Final visit) ] [ Designated as safety issue: No ]
    To evaluate the safety and tolerability of the injectable agent, 744 LA (800 mg dose administered at three time points at 12 week intervals) through Week 41 in HIV-uninfected men as assessed by and injection site reactions (ISRs)


Secondary Outcome Measures:
  • Plasma pharmacokinetic profile for 744 [ Time Frame: Up to Week 41 ] [ Designated as safety issue: No ]
    The following pharmacokinetic parameters were evaluated following each IM injection of 744 LA through 41 weeks. For each 12-week dosing interval, parameters include: Individual plasma PK parameters for each injection interval will be determined, including: area under the plasma concentration time curve over the dosing interval (AUC(0-tau)), maximum observed concentration (Cmax), time to maximum observed concentration (tmax), concentration at the end of the dosing interval (Ctau), and apparent terminal phase half-life for LA administration (t½) and lambda z as a measure of absorption rate constant (lambda z) if data allow

  • 744 PK parameters as assessed by patient demographics (age, race, weight, BMI, and ethnicity) [ Time Frame: Up to Week 41 ] [ Designated as safety issue: No ]
    The following pharmacokinetic parameters following each IM injection of 744 LA through 41 weeks. AUC(0-tau), Ctau, Cmax, t1/2, and lambda z) by age, race, weight, BMI and ethnicity

  • Safety and tolerability of oral 744 [ Time Frame: Up to Week 4 ] [ Designated as safety issue: No ]
    To evaluate the safety and tolerability of oral 744 in HIV-uninfected men as assessed by adverse events, clinical laboratory tests (Hematology/Chemistry testing and Urinalysis) and concurrent medication required

  • Acceptability of 744 LA injections [ Time Frame: Week 5 to Week 41 ] [ Designated as safety issue: No ]
    Acceptability of 744 LA injections was assessed by incidence and severity of ISRs and ISR symptom score

  • Statistical evaluation for concentration-effect relationships for various safety parameters [ Time Frame: Up to Week 81 ] [ Designated as safety issue: No ]
    Pearson's correlations between PK parameters and safety parameters (occurrence of AEs, maximum intensity of AE per subject, and clinical laboratory parameters of special interest) may be presented. Logistic regression may be used to examine correlation between PK parameters and presence or absence of AEs of special interest from selected system organ class


Estimated Enrollment: 120
Study Start Date: March 2014
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
Participants will receive daily oral 744 (30 mg tablets) for 4 weeks, followed by a one week washout period followed by intra-muscular (IM) injections of 800 mg of 744 LA at three time points at 12 week intervals as: Week 5, Week 17, and Week 29
Drug: 744 Tablet
White to almost white oval shaped film coated 30 mg tablets for oral administration
Drug: 744 LA Injection
Sterile white to slightly coloured suspension containing 200 mg/mL of 744 as free acid for administration by intramuscular (IM) injection
Experimental: Arm 2
Participants will receive daily oral matching placebo for 4 weeks, followed by a one week washout period followed by intra-muscular (IM) injections of saline at three time points at 12 week intervals as: Week 5, Week 17, and Week 29
Drug: Placebo Tablet
Microcrystalline cellulose, Opadry film-coating, white OY-S-28876
Drug: Placebo Injection
Sterile saline 0.9% Sodium Chloride Injection

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02076178

Locations
United States, California
GSK Investigational Site
San Francisco, California, United States, 94158
United States, District of Columbia
GSK Investigational Site
Washington, District of Columbia, United States, 20009
United States, Georgia
GSK Investigational Site
Atlanta, Georgia, United States, 30339
United States, Massachusetts
GSK Investigational Site
Boston, Massachusetts, United States, 02215
United States, New Mexico
GSK Investigational Site
Santa Fe, New Mexico, United States, 87505
United States, New York
GSK Investigational Site
New York, New York, United States, 10032
GSK Investigational Site
New York, New York, United States, 10016
GSK Investigational Site
New York, New York, United States, 10065
United States, Pennsylvania
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19104
United States, Virginia
GSK Investigational Site
Newport News, Virginia, United States, 23606
Sponsors and Collaborators
ViiV Healthcare
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials ViiV Healthcare
  More Information

No publications provided

Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT02076178     History of Changes
Other Study ID Numbers: 201120
Study First Received: February 27, 2014
Last Updated: August 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by ViiV Healthcare:
Pre-Exposure Prophylaxis
HIV integrase
Intramuscular Injection
GSK1265744

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Integrase Inhibitors
HIV Integrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 16, 2014