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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)

Completed Phase 2 Results posted Last updated 15 December 2017
What this trial tests

Phase 2 trial testing 744 Tablet in Infection, Human Immunodeficiency Virus in 127 participants. Completed in 23 February 2016.

Timeline
27 March 2014
Primary endpoint
15 May 2015
23 February 2016

Quick facts

Lead sponsorViiV Healthcare
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment127
Start date27 March 2014
Primary completion15 May 2015
Estimated completion23 February 2016
Sites10 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

ViiV Healthcare — full company profile →

Who can join

Adults 18 to 65, male only, with Infection, Human Immunodeficiency Virus. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Any Grade 2 or Higher Event in the Injection Phase Primary · Up to Week 41

Clinical adverse event (AE) were graded using the Division of Acquired Immunodeficiency Syndrome (DAIDS) table for grading the severity of adult and pediatric AE Version 1.0, December 2004; Clarification August 2009. The grades were: 1 (mild)=Symptoms causing no or minimal interference with usual social and functional activities; 2 (moderate)= Symptoms causing greater than minimal interference with usual social and functional activities; 3 (severe)= Symptoms causing inability to perform usual social and functional activities; 4 (potentially life threatening): Symptoms causing inability to perf

GroupValue95% CI
Placebo10
Cabotegravir75
Number of Participants Who Recieved Injection Site Reaction (ISR) Related Concomitant Medication in the Injection Phase Primary · Up to Week 41

The concurrent medications that were consumed by participants during the injection phase were of the class nervous system, musculo-skeletal system, genito urinary systems and sex hormones, various, respiratory system, dermatologicals, alimentary tract and metabolism, sensory organs, systemic hormonal preparations, excluding sex hormones, blood and blood forming organs, cardiovascular system. The participants who took medication from any of the above class of during the injection phase (Week 5-Week 41) have been presented.

GroupValue95% CI
Placebo5
Cabotegravir55
Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase Primary · Up to Week 41

The severity of laboratory results was graded according to the DAIDS table for grading the severity of adult and pediatric AE Version 1.0, December 2004; Clarification August 2009. The DAIDS displays events as Grades 1-5 based on this general guideline: Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, potentially life threatening. Data for Number of participants who experienced grade 2 or higher laboratory results in the injection phase (Week 5-Week 14) have been presented.

Activated prothrombin time/standard
GroupValue95% CI
Placebo1
Cabotegravir0
Activated partial thromboplastin time
GroupValue95% CI
Placebo1
Cabotegravir0
Alanine aminotransferase
GroupValue95% CI
Placebo0
Cabotegravir2
Aspartate aminotransferase
GroupValue95% CI
Placebo0
Cabotegravir2
Bilirubin
GroupValue95% CI
Placebo0
Cabotegravir4
Carbon dioxide
GroupValue95% CI
Placebo0
Cabotegravir1
Cholesterol
GroupValue95% CI
Placebo1
Cabotegravir4
Creatine kinase
GroupValue95% CI
Placebo3
Cabotegravir6
Number of Participants Who Had Abnormal Electrocardiogram (ECG) Findings in the Injection Phase Primary · Up to Week 41

Full 12-lead ECGs included heart rate, PR, QRS, QT and QTc intervals. Measurements were taken from the participant following 5 minutes of rest in a semi-supine position. ECGs were performed at Week 5, Week 17, Week 29 and Week 41 in the injection phase (Week 5-Week 41). ECG abnormalities characterized as abnormal-not clinically significant (A-NCS) and abnormal-clinically significant (A-CS) upto Week 41 have been presented. There were no A-CS findings for ECG in the injection phase.

Week 5, A-NCS
GroupValue95% CI
Placebo6
Cabotegravir30
Week 17, A-NCS
GroupValue95% CI
Placebo9
Cabotegravir34
Week 29, A-NCS
GroupValue95% CI
Placebo7
Cabotegravir27
Week 41, A-NCS
GroupValue95% CI
Placebo5
Cabotegravir23
Change From Baseline in Vital Sign Assessment for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in the Injection Phase Primary · Baseline (Week 5) to Week 41

Vital signs measurements were performed for SBP and DBP following 5 minutes of rest. Baseline was defined as the first injection at Week 5 for the injection phase. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value at Week 17, Week 29 and Week 41.

Week 17, DBP
GroupValue95% CI
Placebo-3.10± 11.541
Cabotegravir-0.74± 7.214
Week 29, DBP
GroupValue95% CI
Placebo-3.75± 12.781
Cabotegravir0.32± 8.283
Week 41, DBP
GroupValue95% CI
Placebo-1.19± 13.692
Cabotegravir0.01± 9.286
Week 17, SBP
GroupValue95% CI
Placebo-1.52± 14.041
Cabotegravir-0.66± 9.237
Week 29, SBP
GroupValue95% CI
Placebo2.80± 10.904
Cabotegravir2.62± 10.868
Week 41, SBP,
GroupValue95% CI
Placebo-1.38± 14.044
Cabotegravir1.64± 12.012
Change From Baseline in Vital Sign Assessment for Heart Rate (HR) in the Injection Phase Primary · Baseline (Week 5) to Week 41

Vital signs measurements were performed for HR following 5 minutes of rest. Baseline was defined as the first injection at Week 5 for the injection phase. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value at Week 17, Week 29 and Week 41.

Week 17, HR
GroupValue95% CI
Placebo1.19± 11.021
Cabotegravir3.26± 11.684
Week 29, HR
GroupValue95% CI
Placebo1.55± 10.149
Cabotegravir4.06± 10.740
Week 41, HR
GroupValue95% CI
Placebo1.43± 10.181
Cabotegravir2.73± 11.752
Number of Participant With ISR for the Injection Phase Defined by Maximum Grades Primary · Up to Week 41

Common ISR included pain, erythema, nodules and any other ISR with greater or equal to 5 participants. The number of participants who experienced pain events by needle length, swelling events by needle length, bump events by needle length for injection phase by maximum grades have been presented for the injection phase (Week 5-Week 41).

ISR pain, Grade 1
GroupValue95% CI
Placebo11
Cabotegravir31
ISR pain, Grade 2
GroupValue95% CI
Placebo1
Cabotegravir37
ISR pain, Grade 3
GroupValue95% CI
Placebo0
Cabotegravir18
ISR pain, Grade 4
GroupValue95% CI
Placebo0
Cabotegravir0
ISR swelling, Grade 1
GroupValue95% CI
Placebo0
Cabotegravir11
ISR swelling, Grade 2
GroupValue95% CI
Placebo0
Cabotegravir4
ISR swelling, Grade 3
GroupValue95% CI
Placebo0
Cabotegravir0
ISR swelling, Grade 4
GroupValue95% CI
Placebo0
Cabotegravir0
Plasma Pharmacokinetic Assessment for Area Under the Plasma Concentration-time Curve Over the Dosing Interval [AUC(0-tau)] in the Injection Phase Secondary · Up to Week 41

Blood samples for pharmacokinetic analysis were collected starting on the first day of the First Injection Phase prior to the injection. At each injection visit a blood sample was collected prior to the injection at Week 5, Week 17 and Week 29, 1 Week post-injection at Week 6, Week 18, and Week 30, and 12 Week post-injection at Week 17, Week 29, and Week 41. The sample collected 12 Week following each injection served as the pre-dose sample for the subsequent dosing interval. Two additional samples were collected 4 and 8 Week after the first injection (Week 9 and Week 13), and 1 additional sam

Injection 1
GroupValue95% CI
Cabotegravir3414.71± 42.5
Injection 2
GroupValue95% CI
Cabotegravir3873.25± 44.3
Injection 3
GroupValue95% CI
Cabotegravir4020.89± 36.2
Plasma Pharmacokinetic Assessment for Concentration at the End of the Dosing Interval (Ctau) and Maximum Observed Concentration (Cmax) in the Injection Phase Secondary · Up to Week 41

Blood samples for pharmacokinetic analysis were collected starting on the first day of the First Injection Phase prior to the injection. At each injection visit a blood sample was collected prior to the injection at Week 5, Week 17 and Week 29, 1 Week post-injection at Week 6, Week 18, and Week 30, and 12 Week post-injection at Week 17, Week 29, and Week 41. The sample collected 12 Week following each injection served as the pre-dose sample for the subsequent dosing interval. Two additional samples were collected 4 and 8 Week after the first injection (Week 9 and Week 13), and 1 additional sam

Cmax, Injection 1
GroupValue95% CI
Cabotegravir4.26± 88.6
Cmax, Injection 2
GroupValue95% CI
Cabotegravir5.22± 78.0
Cmax, Injection 3
GroupValue95% CI
Cabotegravir4.91± 66.6
Ctau, Injection 1
GroupValue95% CI
Cabotegravir0.302± 157.1
Ctau, Injection 2
GroupValue95% CI
Cabotegravir0.331± 164.5
Ctau, Injection 3
GroupValue95% CI
Cabotegravir0.387± 149.6
Plasma Pharmacokinetic Assessment for Time to Maximum Observed Concentration (Tmax), Apparent Terminal Phase Half-life for (t½) in the Injection Phase Secondary · Up to Week 41

Blood samples for pharmacokinetic analysis were collected starting on the first day of the First Injection Phase prior to the injection. At each injection visit a blood sample was collected prior to the injection at Week 5, Week 17 and Week 29, 1 Week post-injection at Week 6, Week 18, and Week 30, and 12 Week post-injection at Week 17, Week 29, and Week 41. The sample collected 12 Week following each injection served as the pre-dose sample for the subsequent dosing interval. Two additional samples were collected 4 and 8 Week after the first injection (Week 9 and Week 13), and 1 additional sam

tmax, Injection 1
GroupValue95% CI
Cabotegravir13.14± 11.503
tmax, Injection 2
GroupValue95% CI
Cabotegravir8.91± 9.311
tmax, Injection 3
GroupValue95% CI
Cabotegravir9.25± 7.579
t½ , Injection 1
GroupValue95% CI
Cabotegravir20.54± 10.690
Plasma Pharmacokinetic Assessment for AUC(0-tau) by Demographic Factor Body Mass Index (BMI) and Needle Length in the Injection Phase Secondary · Up to Week 41

The median BMI was 26 kilogram per meter square. Plasma pharmacokinetic assessments were performed for AUC (0-tau) by BMI, either above or below the median BMI (50 percent upper and lower, where upper summary included all participants with BMI greater than or equal to the median BMI of the population and lower summary included all participants with BMI below the median BMI). Assessments was also performed for AUC (0-tau) by needle length (1.5 inch and 2 inch). Needle length and BMI were correlated in that the longer needle was recommended for participants with BMI greater than 30 kilogram per

50 percent BMI lower, Injection 1
GroupValue95% CI
Cabotegravir4103.71± 28.4
50 percent BMI lower, Injection 2
GroupValue95% CI
Cabotegravir4250.82± 49.6
50 percent BMI lower, Injection 3
GroupValue95% CI
Cabotegravir4847.07± 26.1
50 percent BMI upper, Injection 1
GroupValue95% CI
Cabotegravir2830.06± 45.6
50 percent BMI upper, Injection 2
GroupValue95% CI
Cabotegravir3536.52± 36.7
50 percent BMI upper, Injection 3
GroupValue95% CI
Cabotegravir3405.52± 35.2
1.5 inch Injection 1
GroupValue95% CI
Cabotegravir3666.95± 40.0
1.5 inch Injection 2
GroupValue95% CI
Cabotegravir4177.42± 44.0
Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase Secondary · Up to Week 41

The median BMI was 26 kilogram per meter square. Plasma pharmacokinetic assessments were performed for Ctau and Cmax by BMI, either above or below the median BMI (50 percent upper and lower, where upper summary included all participants with BMI greater than or equal to the median BMI of the population and lower summary included all participants with BMI below the median BMI. ). Assessments was also performed for Ctau and Cmax by needle length (1.5 inch and 2 inch). Needle length and BMI were correlated in that the longer needle was recommended for participants with BMI greater than 30 kilogr

50 percent BMI lower for Cmax, Injection 1
GroupValue95% CI
Cabotegravir6.02± 51.3
50 percent BMI lower for Cmax, Injection 2
GroupValue95% CI
Cabotegravir6.65± 54.8
50 percent BMI lower for Cmax, Injection 3
GroupValue95% CI
Cabotegravir6.99± 35.9
50 percent BMI lower for Ctau, Injection 1
GroupValue95% CI
Cabotegravir0.226± 159.9
50 percent BMI lower for Ctau, Injection 2
GroupValue95% CI
Cabotegravir0.312± 138.3
50 percent BMI lower for Ctau, Injection 3
GroupValue95% CI
Cabotegravir0.334± 102.2
50 percent BMI upper for Cmax, Injection 1
GroupValue95% CI
Cabotegravir2.99± 100.0
50 percent BMI upper for Cmax, Injection 2
GroupValue95% CI
Cabotegravir4.12± 88.4

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to Week 41. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 1/21 (5%)
Deaths: 0/21
Cabotegravir
Serious: 1/105 (1%)
Deaths: 0/105

Serious adverse events (2 terms)

ReactionSystemPlaceboCabotegravir
AppendicitisInfections and infestations
Deep vein thrombosisVascular disorders
Other adverse events (26 terms — click to expand)

ReactionSystemPlaceboCabotegravir
Injection site painGeneral disorders
HeadacheNervous system disorders
Injection site swellingGeneral disorders
Upper respiratory tract infectionInfections and infestations
Injection site pruritusGeneral disorders
PyrexiaGeneral disorders
FatigueGeneral disorders
DiarrhoeaGastrointestinal disorders
NasopharyngitisInfections and infestations
Injection site warmthGeneral disorders
Injection site bruisingGeneral disorders
Viral upper respiratory tract infectionInfections and infestations
Injection site indurationGeneral disorders
MyalgiaMusculoskeletal and connective tissue disorders
Blood creatine phosphokinase increasedInvestigations
NeutropeniaBlood and lymphatic system disorders
NauseaGastrointestinal disorders
Seasonal allergyImmune system disorders
ChillsGeneral disorders
Injection site erythemaGeneral disorders
GastroenteritisInfections and infestations
DizzinessNervous system disorders
Rhinitis allergicRespiratory, thoracic and mediastinal disorders
Nasal congestionRespiratory, thoracic and mediastinal disorders
SinusitisInfections and infestations
InsomniaPsychiatric disorders

Most-reported serious reactions: Appendicitis, Deep vein thrombosis.

Data from ClinicalTrials.gov NCT02076178 adverse events section.

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Safety and tolerability of long-acting cabotegravir injections in HIV-uninfected men (ECLAIR): a multicentre, double-blind, randomised, placebo-controlled, phase 2a trial.
    Markowitz M, Frank I, Grant RM, Mayer KH, et al · · 2017 · cited 159× · PMID 28546090 · DOI 10.1016/s2352-3018(17)30068-1
  2. Familiarity with and Preferences for Oral and Long-Acting Injectable HIV Pre-exposure Prophylaxis (PrEP) in a National Sample of Gay and Bisexual Men in the U.S.
    Parsons JT, Rendina HJ, Whitfield TH, Grov C. · · 2016 · cited 94× · PMID 27000145 · DOI 10.1007/s10461-016-1370-5
  3. Long-acting injectable cabotegravir for the prevention of HIV infection.
    Clement ME, Kofron R, Landovitz RJ. · · 2020 · cited 79× · PMID 31644481 · DOI 10.1097/coh.0000000000000597
  4. Creation of a nanoformulated cabotegravir prodrug with improved antiretroviral profiles.
    Zhou T, Su H, Dash P, Lin Z, et al · · 2018 · cited 66× · PMID 29059541 · DOI 10.1016/j.biomaterials.2017.10.023
  5. Will Gay and Bisexual Men Taking Oral Pre-exposure Prophylaxis (PrEP) Switch to Long-Acting Injectable PrEP Should It Become Available?
    John SA, Whitfield THF, Rendina HJ, Parsons JT, et al · · 2018 · cited 59× · PMID 28913659 · DOI 10.1007/s10461-017-1907-2
  6. Satisfaction and acceptability of cabotegravir long-acting injectable suspension for prevention of HIV: Patient perspectives from the ECLAIR trial.
    Murray MI, Markowitz M, Frank I, Grant RM, et al · · 2018 · cited 56× · PMID 30445896 · DOI 10.1080/15284336.2018.1511346
  7. Willingness of community-recruited men who have sex with men in Washington, DC to use long-acting injectable HIV pre-exposure prophylaxis.
    Levy ME, Patrick R, Gamble J, Rawls A, et al · · 2017 · cited 40× · PMID 28827821 · DOI 10.1371/journal.pone.0183521
  8. Preventive efficacy of a tenofovir alafenamide fumarate nanofluidic implant in SHIV-challenged nonhuman primates.
    Pons-Faudoa FP, Sizovs A, Shelton KA, Momin Z, et al · · 2021 · cited 34× · PMID 33997267 · DOI 10.1002/adtp.202000163

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02076178.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing