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Evaluating the Safety, Tolerability, and Pharmacokinetics of an Investigational, Injectable HIV Medicine (GSK1265744) in HIV-Uninfected Adults

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT02178800
First received: June 27, 2014
Last updated: December 5, 2016
Last verified: December 2016
  Purpose
This study will evaluate the safety, tolerability, and pharmacokinetics (which is how the body interacts with drugs) of an investigational, injectable HIV medicine (GSK1265744) in healthy, HIV-uninfected adults. Researchers will evaluate the use of this medicine for both the prevention and treatment of HIV infection.

Condition Intervention Phase
HIV Infections
Drug: GSK1265744 Tablets
Drug: Injectable GSK1265744
Drug: Placebo for GSK1265744 Tablets
Drug: Injectable Placebo for GSK1265744
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Phase IIa Study to Evaluate the Safety, Tolerability and Pharmacokinetics of the Investigational Injectable HIV Integrase Inhibitor, GSK1265744, in HIV-uninfected Men and Women

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Proportion of participants experiencing any Grade 2 or higher clinical adverse events (AEs) and laboratory abnormalities that occur from the initial injection to Week 41 among participants who receive at least one injection (injectable phase only) [ Time Frame: Measured through Week 41 ] [ Designated as safety issue: Yes ]
  • Proportion of participants who receive at least 1 injection and who discontinue receiving injections prior to the full course of injections [ Time Frame: Measured through Week 85 ] [ Designated as safety issue: No ]
    Due to intolerability of injection (including but not limited to injection site reaction [ISR]), frequency of injections, burden of study procedures, or any AE


Secondary Outcome Measures:
  • Proportion of participants who discontinue either oral or injectable study product for reasons of toxicity, tolerability, or acceptability prior to completion of the full oral and injectable phases [ Time Frame: Measured through Week 81 for Cohort 1 and Week 85 for Cohort 2 ] [ Designated as safety issue: Yes ]
  • Proportion of participants experiencing Grade 2 or higher clinical AEs and laboratory abnormalities during 52 weeks following final injection (safety) and any AE that leads to discontinuation (tolerability) during the aggregate oral and injectable phases [ Time Frame: Measured through Week 81 for Cohort 1 and Week 85 for Cohort 2 ] [ Designated as safety issue: Yes ]
  • Proportion of participants experiencing Grade 2 or higher clinical AEs and laboratory abnormalities (safety) and any AE that leads to discontinuation (tolerability) in the oral phase and washout period [ Time Frame: Measured through Week 5 ] [ Designated as safety issue: Yes ]
  • Plasma drug levels of GSK1265744 at designated time points after each injection of 744LA (injectable formulation of GSK1265744) [ Time Frame: Measured through Week 81 for Cohort 1 and Week 85 for Cohort 2 ] [ Designated as safety issue: No ]
    Stratified by age, gender, race, ethnicity, weight, body mass index (BMI), and smoking status (by cohort only)

  • Proportion of participants willing to use an injectable agent such as the study product for HIV prevention in the future [ Time Frame: Measured through Week 81 for Cohort 1 and Week 85 for Cohort 2 ] [ Designated as safety issue: No ]
  • Change from enrollment of self-reported sexual behavior (number of sexual partners, episodes of unprotected anal and/or vaginal intercourse) during the study period using a standardized assessment tool (in aggregate only) [ Time Frame: Measured through Week 81 for Cohort 1 and Week 85 for Cohort 2 ] [ Designated as safety issue: No ]
  • Number of incident HIV infections through the study period, including number with treatment emergent resistance [ Time Frame: Measured through Week 81 for Cohort 1 and Week 85 for Cohort 2 ] [ Designated as safety issue: No ]
  • Proportion of injectable hormonal-contraception-using female participants who reach a safety or tolerability endpoint as defined above [ Time Frame: Measured through Week 81 for Cohort 1 and Week 85 for Cohort 2 ] [ Designated as safety issue: No ]

Estimated Enrollment: 194
Study Start Date: February 2015
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1: GSK1265744
Participants in Cohorts 1 and 2 will receive one GSK1265744 tablet orally every day from study entry through Week 4. They will then receive an injection of GSK1265744—at Weeks 5, 17, and 29 for participants in Cohort 1 and at Weeks 5, 9, 17, 25, and 33 for participants in Cohort 2.
Drug: GSK1265744 Tablets
30-mg tablets, taken orally
Other Name: Oral 744
Drug: Injectable GSK1265744

Cohort 1: 800-mg injection, administered as two 400-mg intramuscular (IM) gluteal injections

Cohort 2: 600-mg injection, administered as one IM gluteal injection

Other Names:
  • GSK1265744 long acting
  • 744LA
Placebo Comparator: Group 2: Placebo
Participants in Cohorts 1 and 2 will receive one placebo tablet orally every day from study entry through Week 4. They will then receive an injection of placebo—at Weeks 5, 17, and 29 for participants in Cohort 1 and at Weeks 5, 9, 17, 25, and 33 for participants in Cohort 2.
Drug: Placebo for GSK1265744 Tablets
Taken orally
Drug: Injectable Placebo for GSK1265744

Cohort 1: Sodium Chloride for Injection USP, 0.9%; administered as two 400-mg IM gluteal injections

Cohort 2: Sodium Chloride for Injection USP, 0.9%; administered as one 600-mg IM gluteal injection


Detailed Description:

This study will evaluate GSK1265744, which is an investigational, injectable HIV medicine. The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of GSK1265744 in healthy, HIV-uninfected adults. Study researchers will evaluate the use of GSK1265744 for both the prevention of HIV infection (known as pre-exposure prophylaxis [PrEP]) and for the treatment for HIV infection.

This study will enroll two cohorts of participants (Cohort 1 and Cohort 2). Within each cohort, participants will be randomly assigned to one of two groups: Group 1 will receive GSK1265744 tablets (also called oral 744) and injections (also called GSK1265744 long acting or 744LA), and Group 2 will receive placebo tablets and injections. Participants in Cohort 1 will attend several study visits through Week 81 or Week 105. Participants in Cohort 2 will attend several study visits through Week 85 or Week 109. From study entry through Week 4, participants in both cohorts will take a GSK1265744 tablet (Group 1) or a placebo tablet (Group 2) once a day. For 1 week after participants stop taking their assigned tablets, study researchers will assess safety and tolerability. If no safety or tolerability concerns are identified, participants will enter the injection phase of the study. Participants in Cohort 1 will receive two injections of GSK1265744 (Group 1) or placebo (Group 2) at Weeks 5, 17, and 29. Participants in Cohort 2 will receive one injection of GSK1265744 (Group 1) or placebo (Group 2) at Weeks 5, 9, 17, 25, and 33.

All study visits will include HIV counseling, a physical examination, a medical history review, and a blood collection. Select study visits will include adherence counseling, central nervous system (CNS) symptom assessment, behavioral and acceptability assessments, a urine collection, an electrocardiogram (ECG), and rectal and/or vaginal swabs.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Men and women, 18 to 65 years old at the time of screening
  • Willing to provide informed consent for the study
  • In the last 12 months (at the time of screening):

    • No self-reported unprotected anal or vaginal intercourse with someone known to be HIV-infected or of unknown HIV infection status
    • No self-reported stimulant use (cocaine [including crack], methamphetamine, or non-physician-prescribed pharmaceutical-grade stimulants) or inhaled nitrate
    • No self-reported illicit injection drug use of any kind
    • No self-reported diagnosis of gonorrhea (GC), chlamydia (CT), incident syphilis, bacterial vaginosis, or trichomoniasis
    • Not reporting five or more different sexual partners, regardless of use of protection or knowledge of HIV status. More information on this criterion is available in the protocol.
  • In general good health, as evidenced by the following laboratory values, which must be from specimens obtained within 45 days prior to study enrollment:

    • Non-reactive/negative HIV test results. More information on this criterion is available in the protocol.
    • Hemoglobin greater than 11 g/dL
    • Absolute neutrophil count greater than 750 cells/mm^3
    • Platelet count greater than or equal to 100,000/mm^3
    • Calculated creatinine clearance greater than or equal to 70 mL/minute using the Cockcroft-Gault equation
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to the upper limit of normal (ULN)
    • Total bilirubin less than or equal to Grade 1 and direct bilirubin less than or equal to ULN
    • Hepatitis B surface antigen (HBsAg) negative
    • Hepatitis C Ab negative
    • Note: Chemistry and hematology parameters which do not meet the inclusion criteria above may be repeated once during screening.
  • No alcohol or substance use that, in the opinion of the study investigator, would interfere with the conduct of the study (e.g., provided by self-report, or found upon medical history and examination or in available medical records). More information on this criterion is available in the protocol.
  • No medical condition that, in the opinion of the study investigator, would interfere with the conduct of the study (e.g., provided by self-report, or found upon medical history and examination or in available medical records)
  • Willing to undergo all required study procedures

Additional requirements for all women:

  • If of reproductive potential (defined as pre-menopausal women who have not had a sterilization procedure per self-report, such as hysterectomy, bilateral oophorectomy, tubal ligation, or salpingectomy), must have a negative urine pregnancy test performed (and results known) within 48 hours before initiating the protocol-specified medication(s) at enrollment. Women are considered menopausal if they have not had a menses for at least 12 months and have a follicle stimulating hormone (FSH) level of greater than 40 IU/L; if FSH testing is not available, they must have had amenorrhea for 24 or more consecutive months. (FSH testing is not a protocol requirement.)
  • If of reproductive potential and participating in sexual activity that could lead to pregnancy, women must agree to use a form of contraception during the trial and for 30 days after stopping the oral study medication or for 52 weeks after stopping the long acting injectable from the list below:

    • Intrauterine device (IUD) or intrauterine system (IUS) that meets less than 1% failure rate as stated in the product label
    • Hormone-based contraceptive

Exclusion Criteria:

  • One or more reactive or positive HIV test result at Screening or Enrollment, even if HIV infection is not confirmed
  • Any active sexually transmitted infection detected by laboratory testing at Screening
  • Co-enrollment in any other HIV interventional research study or other concurrent studies which may interfere with this study (as provided by self-report or other available documentation; exceptions may be made if appropriate after consultation with the Clinical Management Committee [CMC].)
  • Past or current participation in HIV vaccine trial. An exception will be made for participants that can provide documentation of receipt of placebo (not active arm).
  • Use of antiretroviral therapy (ART) (e.g., for non-occupational post-exposure prophylaxis [PEP] or PrEP) in the 90 days prior to study entry
  • Clinically significant cardiovascular disease, including:
  • ECG (one repeat ECG is allowed during screening; may be performed on the same day) with:

    • heart rate less than 45 or greater than 100 beats per minute for men, and less than 50 or greater than 100 beats per minute for women
    • interval from the beginning of the Q wave to the end of the S wave (QRS) duration greater than 120 msec
    • corrected QT (QTc) interval (B or F) greater than 450 msec
    • evidence of previous myocardial infarction (pathologic Q waves, S-T segment changes) (except early repolarization)
    • any clinically significant conduction abnormality (including but not specific to left or right complete bundle branch block, atrioventricular [AV] block [2nd degree (type II) or higher], Wolf Parkinson White [WPW] syndrome) (any question of clinical significance should be referred to the CMC for adjudication)
    • sinus pauses greater than 3 seconds
    • any clinically significant arrhythmia that, in the opinion of the Investigator of Record (IoR) or designee, will interfere with the safety for the individual participant (any question of clinical significance should be referred to the CMC for adjudication)
    • or history of non-sustained (greater than or equal to 3 consecutive ventricular ectopic beats on ECG at screening or entry) or sustained ventricular tachycardia
  • History/evidence of symptomatic arrhythmia, angina/ischemia, coronary artery bypass grafting (CABG) surgery or percutaneous transluminal coronary angioplasty (PTCA) or any clinically significant cardiac disease
  • Systolic blood pressure at screening outside the range of 90 to 140 mm Hg or diastolic blood pressure outside the range of 45 to 90 mm Hg (confirmed on repeat measurement)
  • Underlying skin disease or currently active skin disorder (e.g., infection, inflammation, dermatitis, eczema, psoriasis, urticaria). Mild cases of localized acne or folliculitis or other mild skin condition may not be exclusionary at the discretion of the IoR or designee in consultation with the CMC.
  • Has a tattoo or other dermatological condition overlying the buttock region that in the opinion of the IoR or designee, in consultation with the CMC, may interfere with interpretation of injection site reactions
  • Current or chronic history of liver disease (e.g., non-alcoholic or alcoholic steatohepatitis) or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome, asymptomatic gallstones, or cholecystectomy)
  • Coagulopathy (primary or iatrogenic) that would contraindicate IM injection (concomitant anticoagulant or anti-platelet therapy use should be discussed with the CMC)
  • Active or planned use of prohibited medications as described in the Investigator's Brochure or listed in the Study Specific Procedures (SSP) Manual (provided by self-report, or obtained from medical history or medical records)
  • A score of greater than or equal to 8 on the WHO Alcohol Use Disorders Identification Test (AUDIT) at screening. Note: A score of greater than or equal to 8 indicates a medium to high level of problem alcohol use.
  • For women: pregnant or currently breastfeeding, or intends to become pregnant and/or breastfeed during the study
  • A history of seizure disorder, by self-report
  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: NCT02178800

Locations
United States, California
UCLA CARE Center CRS
Los Angeles, California, United States, 90035
Bridge HIV CRS
San Francisco, California, United States, 94143
United States, District of Columbia
George Washington Univ. CRS
Washington, District of Columbia, United States, 20006
United States, North Carolina
Chapel Hill CRS
Chapel Hill, North Carolina, United States, 27599
Brazil
Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS
Rio de Janeiro, Brazil, 21040-360
Malawi
Malawi CRS
Lilongwe, Malawi
South Africa
Soweto HPTN CRS
Johannesburg, Gauteng, South Africa, 1862
Vulindlela CRS
Durban, KwaZulu-Natal, South Africa, 4013
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Study Chair: Raphael J. Landovitz, MD, MSc University of California, Los Angeles
  More Information

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT02178800     History of Changes
Other Study ID Numbers: HPTN 077  11964 
Study First Received: June 27, 2014
Last Updated: December 5, 2016
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on December 09, 2016