Clinical trial NCT02076178: 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)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Infection, Human Immunodeficiency Virus
Keywords: Pre-Exposure Prophylaxis
HIV integrase
Intramuscular Injection
GSK1265744
Lead sponsor: ViiV Healthcare
Sponsor class: INDUSTRY
Collaborators: name: GlaxoSmithKline
First posted: 2014-03-03
Enrollment: 127
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Primary outcomes:
measure: Number of Participants With Any Grade 2 or Higher Event in the Injection Phase
timeFrame: Up to Week 41
measure: Number of Participants Who Recieved Injection Site Reaction (ISR) Related Concomitant Medication in the Injection Phase
timeFrame: Up to Week 41
measure: Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase
timeFrame: Up to Week 41
measure: Number of Participants Who Had Abnormal Electrocardiogram (ECG) Findings in the Injection Phase
timeFrame: Up to Week 41
measure: Change From Baseline in Vital Sign Assessment for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in the Injection Phase
timeFrame: Baseline (Week 5) to Week 41
measure: Change From Baseline in Vital Sign Assessment for Heart Rate (HR) in the Injection Phase
timeFrame: Baseline (Week 5) to Week 41
measure: Number of Participant With ISR for the Injection Phase Defined by Maximum Grades
timeFrame: Up to Week 41
Secondary outcomes:
measure: Plasma Pharmacokinetic Assessment for Area Under the Plasma Concentration-time Curve Over the Dosing Interval [AUC(0-tau)] in the Injection Phase
timeFrame: Up to Week 41
measure: Plasma Pharmacokinetic Assessment for Concentration at the End of the Dosing Interval (Ctau) and Maximum Observed Concentration (Cmax) in the Injection Phase
timeFrame: Up to Week 41
measure: Plasma Pharmacokinetic Assessment for Time to Maximum Observed Concentration (Tmax), Apparent Terminal Phase Half-life for (t½) in the Injection Phase
timeFrame: Up to Week 41
measure: Plasma Pharmacokinetic Assessment for AUC(0-tau) by Demographic Factor Body Mass Index (BMI) and Needle Length in the Injection Phase
timeFrame: Up to Week 41
measure: Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase
timeFrame: Up to Week 41
measure: Plasma Pharmacokinetic Assessment for Tmax and t½ by Demographic Factor BMI and Needle Length in the Injection Phase
timeFrame: Up to Week 41
measure: Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length
timeFrame: Up to Week 41
measure: Number of Participants With AE, Grade 2-4 AE and Serious Adverse Events (SAE) in the Oral Phase
timeFrame: Up to Week 4
measure: Number of Participants Who Received Concurrent Medication in Overall Study Duration
timeFrame: Up to Week 41
measure: Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades
timeFrame: Up to Week 4
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: GSK Investigational Site
state: California
city: Washington
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Santa Fe
country: United States
facility: GSK Investigational Site
state: New Mexico
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Newport News
country: United States
facility: GSK Investigational Site
state: Virginia
Study officials:
affiliation: ViiV Healthcare
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Murray MI, Markowitz M, Frank I, Grant RM, Mayer KH, Hudson KJ, Stancil BS, Ford SL, Patel P, Rinehart AR, Spreen WR, Margolis DA. Satisfaction and acceptability of cabotegravir long-acting injectable suspension for prevention of HIV: Patient perspectives from the ECLAIR trial. HIV Clin Trials. 2018 Aug;19(4):129-138. doi: 10.1080/15284336.2018.1511346. Epub 2018 Nov 16.
citation: Markowitz M, Frank I, Grant RM, Mayer KH, Elion R, Goldstein D, Fisher C, Sobieszczyk ME, Gallant JE, Van Tieu H, Weinberg W, Margolis DA, Hudson KJ, Stancil BS, Ford SL, Patel P, Gould E, Rinehart AR, Smith KY, Spreen WR. Safety and tolerability of long-acting cabotegravir injections in HIV-uninfected men (ECLAIR): a multicentre, double-blind, randomised, placebo-controlled, phase 2a trial. Lancet HIV. 2017 Aug;4(8):e331-e340. doi: 10.1016/S2352-3018(17)30068-1. Epub 2017 May 22.