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

NCT02178800 | Completed Phase 2 Results DMC

• 2 other identifiers: HPTN 07711964
• Study Type: interventional
• Target: 199
• Locations: 4 countries
• Sites: 8

Brief Summary

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.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (3)

• Number 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)

  An adverse events (AE) or laboratory abnormality can be an unfavorable or unintended sign, symptom or disease temporally associated with the use of an investigational product, whether or not considered related to the product. AE severity was graded per the DAIDS Table for Grading Adult and Pediatric Adverse Events, Version 2.0, November 2014. The outcome in this table is stratified by arm.

  Measured through Week 41

• Number of Participants Who Discontinue Injectable Study Product for Reasons of Toxicity, Tolerability, or Acceptability That Occur From the Initial Injection to Week 41 Among Participants Who Receive at Least One Injection (Injectable Phase Only)

  Stratified by arm

  Measured through Week 41

• Plasma Drug Levels of GSK1265744 at Designated Time Points After Each Injection of 744LA (Injectable Formulation of GSK1265744)

  Geometric means and 90% prediction intervals by sex at birth and cohort are reported.

  Measured through Week 41

Secondary Outcomes (10)

• Number of Participants Experiencing Grade 2 or Higher Clinical Adverse Events (AEs) and Laboratory Abnormalities During Tail Phase

  Measured from 12 weeks after last injection through Week 105 for Cohort 1 and 8 weeks after last injection through Week 109 for Cohort 2

• Number of Participants Experiencing Grade 2 or Higher Clinical Adverse Events (AEs) and Laboratory Abnormalities Prior to Completion of the Oral Phase

  Measured through Week 5

• Number of Participants Willing to Use an Injectable Agent Such as the Study Product for HIV Prevention in the Future

  Measured from week 6 through Week 30 in cohort 1 and Week 34 in cohort 2

• Number of Participants With HIV Infections Through the Study Period, Stratified by Arm

  Measured through Week 105 for Cohort 1 and Week 109 for Cohort 2

• Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period

  Measured through Week 77

Study Arms (2)

Group 1: GSK1265744

EXPERIMENTAL

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; Drug: Injectable GSK1265744

Group 2: Placebo

PLACEBO COMPARATOR

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; Drug: Injectable Placebo for GSK1265744

Interventions

GSK1265744 Tablets DRUG

30-mg tablets, taken orally

Also known as: Oral 744

Group 1: GSK1265744

Injectable GSK1265744 DRUG

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

Also known as: GSK1265744 long acting, 744LA

Group 1: GSK1265744

Placebo for GSK1265744 Tablets DRUG

Taken orally

Group 2: Placebo

Injectable Placebo for GSK1265744 DRUG

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

Group 2: Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (8)

UCLA CARE Center CRS

Los Angeles, California, 90035, United States

Location

Bridge HIV CRS

San Francisco, California, 94143, United States

Location

George Washington Univ. CRS

Washington D.C., District of Columbia, 20006, United States

Location

Chapel Hill CRS

Chapel Hill, North Carolina, 27599, United States

Location

Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS

Rio de Janeiro, 21040-360, Brazil

Location

Malawi CRS

Lilongwe, Malawi

Location

Soweto HPTN CRS

Johannesburg, Gauteng, 1862, South Africa

Location

Vulindlela CRS

Durban, KwaZulu-Natal, 4013, South Africa

Location

Related Publications (2)

• Landovitz RJ, Li S, Eron JJ Jr, Grinsztejn B, Dawood H, Liu AY, Magnus M, Hosseinipour MC, Panchia R, Cottle L, Chau G, Richardson P, Marzinke MA, Eshleman SH, Kofron R, Adeyeye A, Burns D, Rinehart AR, Margolis D, Cohen MS, McCauley M, Hendrix CW. Tail-phase safety, tolerability, and pharmacokinetics of long-acting injectable cabotegravir in HIV-uninfected adults: a secondary analysis of the HPTN 077 trial. Lancet HIV. 2020 Jul;7(7):e472-e481. doi: 10.1016/S2352-3018(20)30106-5. Epub 2020 Jun 1.

  PMID: 32497491 DERIVED

• Landovitz RJ, Li S, Grinsztejn B, Dawood H, Liu AY, Magnus M, Hosseinipour MC, Panchia R, Cottle L, Chau G, Richardson P, Marzinke MA, Hendrix CW, Eshleman SH, Zhang Y, Tolley E, Sugarman J, Kofron R, Adeyeye A, Burns D, Rinehart AR, Margolis D, Spreen WR, Cohen MS, McCauley M, Eron JJ. Safety, tolerability, and pharmacokinetics of long-acting injectable cabotegravir in low-risk HIV-uninfected individuals: HPTN 077, a phase 2a randomized controlled trial. PLoS Med. 2018 Nov 8;15(11):e1002690. doi: 10.1371/journal.pmed.1002690. eCollection 2018 Nov.

  PMID: 30408115 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

cabotegravir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: Gordon Chau
• Organization: Fred Hutch Cancer Research Center

gchau@fredhutch.org

2066672118

Study Officials

• Raphael J. Landovitz, MD, MSc

  University of California, Los Angeles

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2014
• First Posted: July 1, 2014
• Study Start: February 1, 2015
• Primary Completion: April 5, 2017
• Study Completion: July 13, 2018
• Last Updated: October 18, 2021
• Results First Posted: July 5, 2018

Record last verified: 2021-10

Locations

MA (1); ZA (2); US (4); BR (1)