A Study to Investigate Pharmacokinetics, Safety and Tolerability of Long-Acting Cabotegravir Plus Recombinant Human Hyaluronidase PH20 in Healthy Adult Participants

NCT05418868 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 218012
• Study Type: interventional
• Target: 214
• Locations: 1 country
• Sites: 3

Brief Summary

This is an open-label, dose-escalation study to investigate the safety, tolerability and pharmacokinetics (PK) of single subcutaneous (SC) administration of long acting (LA) Cabotegravir (CAB) 200 milligrams per milliliter (mg/mL) with Recombinant Human Hyaluronidase PH20 (rHuPH20) (Part A), a single-dose or repeat-dose SC or intramuscular (IM) administration of LA CAB (greater than or equal to) \>=400 mg/mL (Part C), single-dose IM administration of LA CAB Formulation I (Part C Cohort C8) and LA CAB Formulation J (Part C Cohort C11), and a single-dose or repeat-dose IM administration of rilpivirine (RPV) (Part E). Part A of the study (CAB 200 mg/mL with rHuPh20) has been closed to further enrolment based on preliminary results. Part D of the study (CAB \>=400 mg/mL with rHuPH20) will not be conducted due to changes in the study design.

Conditions

HIV Infections

Keywords

Cabotegravir (CAB); Rilpivirine (RPV); Long-Acting Injection; Pharmacokinetics; Safety; Tolerability

Outcome Measures

Primary Outcomes (45)

• Maximum observed plasma concentration (Cmax) of CAB and RPV

  Up to end of study (Week 78 for Cohorts C1 and C3 [Part C], Week 52 for Part A, Cohorts C2, C4, C5, C6, C7, C8, C9 [Part C], and Week 72 for Part E and Cohorts C10 and C11 [Part C])

• Time of maximum observed plasma concentration (tmax) of Cabotegravir CAB and RPV

  Up to end of study (Week 78 for Cohorts C1 and C3 [Part C], Week 52 for Part A, Cohorts C2, C4, C5, C6, C7, C8, C9 [Part C], and Week 72 for Part E and Cohorts C10 and C11 [Part C])

• Area under the concentration - time curve from time zero to infinity (AUC[0-inf]) of CAB and RPV

  Up to end of study (Week 78 for Cohorts C1 and C3 [Part C], Week 52 for Part A, Cohorts C2, C4, C5, C6, C7, C8, C9 [Part C], and Week 72 for Part E and Cohorts C10 and C11 [Part C])

• Area under the concentration - time curve from time zero to time of last quantifiable concentration or 4 weeks following the injection whichever is earlier (AUC[0-t]) of CAB and RPV

  Up to end of study (Week 78 for Cohorts C1 and C3 [Part C], Week 52 for Cohorts Part A, C2, C4, C5, C6, C7, C8, C9 [Part C], and Week 72 for Part E and Cohort C10 [Part C])

• Area under the concentration - time curve from time zero to last quantifiable time point or 8 weeks following the injection whichever is earlier [AUC(0-t)]

  Up to end of study (Week 72 for Cohort C10 [Part C])

• Plasma Concentration of CAB and RPV at Week 4

  Week 4

• Plasma Concentration of CAB and RPV at Week 8

  Week 8

• Plasma Concentration of CAB and RPV at Week 12

  Week 12

• Plasma Concentration of CAB and RPV at Week 16

  Week 16

• Plasma Concentration of CAB and RPV at Week 24

  Week 24

• Plasma Concentration of RPV at Week 32

  Week 32

• Plasma Concentration of CAB at Week 36

  Week 36

• Plasma Concentration of RPV at Week 40

  Week 40

• Plasma Concentration of CAB and RPV at Week 48

  Week 48

• Plasma Concentration of CAB

  At weeks 56, 64 and 72 for Cohorts C11 and C10 [Part C]

• Plasma Concentration of RPV at Week 56

  Week 56

• Plasma Concentration of RPV at Week 64

  Week 64

• Plasma Concentration of RPV at Week 72

  Week 72

• Apparent terminal phase half-life (t1/2) of CAB and RPV

  Up to end of study (Week 78 for Cohorts C1 and C3 [Part C], Week 52 for Part A, Cohorts C2, C4, C5, C6, C7, C8, C9 [Part C], and Week 72 for Part E and Cohorts C10 and C11 [Part C])

• Apparent long-acting absorption rate constant (KA-LA) of CAB and RPV

  Up to end of study (Week 78 for Cohorts C1 and C3 [Part C], Week 52 for Part A, Cohorts C2, C4, C5, C6, C7, C8, C9 [Part C], and Week 72 for Part E and Cohorts C10 and C11 [Part C])

• Number of Participants with Non-serious Adverse Events (non-SAEs) and Serious Adverse Events (SAEs)

  Up to end of study (Week 78 for Cohorts C1 and C3 [Part C], Week 52 for Part A, Cohorts C2, C4, C5, C6, C7, C8, C9 [Part C], and Week 72 for Part E and Cohorts C10 and C11 [Part C])

• Number of Participants with AEs by Severity

  Up to end of study (Week 78 for Cohorts C1 and C3 [Part C], Week 52 for Part A, Cohorts C2, C4, C5, C6, C7, C8, C9 [Part C], and Week 72 for Part E and Cohorts C10 and C11 [Part C])

• Absolute value of Hematology parameter: Platelet count (cells per microliter)

  Up to end of study (Week 78 for Cohorts C1 and C3 [Part C], Week 52 for Part A, Cohorts C2, C4, C5, C6, C7, C8, C9 [Part C], and Week 72 for Part E and Cohorts C10 and C11 [Part C])

• Absolute values of Hematology parameters: Reticulocytes (Percentage of reticulocytes)

  Up to end of study (Week 78 for Cohorts C1 and C3 [Part C], Week 52 for Part A, Cohorts C2, C4, C5, C6, C7, C8, C9 [Part C], and Week 72 for Part E and Cohorts C10 and C11 [Part C])

• Absolute values of Hematology parameters: Hematocrit (Proportion of red blood cells in blood)

  Up to end of study (Week 78 for Cohorts C1 and C3 [Part C], Week 52 for Part A, Cohorts C2, C4, C5, C6, C7, C8, C9 [Part C], and Week 72 for Part E and Cohorts C10 and C11 [Part C])

• Absolute values of Hematology parameters: Hemoglobin (Hgb) (grams per deciliter)

  Up to end of study (Week 78 for Cohorts C1 and C3 [Part C], Week 52 for Part A, Cohorts C2, C4, C5, C6, C7, C8, C9 [Part C] , and Week 72 for Part E and Cohorts C10 and C11 [Part C])

• Absolute value of Hematology parameter: Red Blood Cell Count (RBC) (million cells per microliter)

  Up to end of study (Week 78 for Cohorts C1 and C3 [Part C], Week 52 for Part A, Cohorts C2, C4, C5, C6, C7, C8, C9 [Part C] , and Week 72 for Part E and Cohorts C10 and C11 [Part C])

• Absolute value of Hematology parameter: Mean Corpuscle Volume (MCV) (Femtoliters)

  Up to end of study (Week 78 for Cohorts C1 and C3 [Part C], Week 52 for Part A, Cohorts C2, C4, C5, C6, C7, C8, C9 [Part C] , and Week 72 for Part E and Cohorts C10 and C11 [Part C])

• Absolute value of Hematology parameter: Mean Corpuscle Hemoglobin (MCH) (Picograms)

  Up to end of study (Week 78 for Cohorts C1 and C3 [Part C], Week 52 for Part A, Cohorts C2, C4, C5, C6, C7, C8, C9 [Part C], and Week 72 for Part E and Cohorts C10 and C11 [Part C])

• Absolute values of Hematology parameters: Differential count of Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils (giga cells per liter)

  Up to end of study (Week 78 for Cohorts C1 and C3 [Part C], Week 52 for Part A, Cohorts C2, C4, C5, C6, C7, C8, C9 [Part C], and Week 72 for Part E and Cohorts C10 and C11 [Part C])

• Absolute values of Clinical Chemistry parameters: Glucose (fasting), Blood Urea Nitrogen (BUN), Creatinine, Sodium, Potassium, Calcium, Direct Bilirubin and Total Bilirubin (milligrams per deciliter)

  Up to end of study (Week 78 for Cohorts C1 and C3 [Part C], Week 52 for Part A, Cohorts C2, C4, C5, C6, C7, C8, C9 [Part C], and Week 72 for Part E and Cohorts C10 and C11 [Part C])

• Absolute values of Clinical Chemistry parameters: AST/SGOT, ALT/ SGPT, ALP and CPK (International Units per liter)

  Clinical chemistry parameters such as Aspartate Aminotransferase (AST) / Serum Glutamic-Oxaloacetic Transaminase (SGOT), Alanine Aminotransferase (ALT)/ Serum Glutamic-Pyruvic Transaminase and (SGPT), Alkaline phosphatase (ALP) and Creatinine Phosphokinase (CPK) will be analyzed.

  Up to end of study (Week 78 for Cohorts C1 and C3 [Part C], Week 52 for Part A, Cohorts C2, C4, C5, C6, C7, C8, C9 [Part C], and Week 72 for Part E and Cohorts C10 and C11 [Part C])

• Absolute values of Clinical chemistry parameters: Albumin and Total Protein (Grams per deciliter)

  Up to end of study (Week 78 for Cohorts C1 and C3 [Part C], Week 52 for Part A, Cohorts C2, C4, C5, C6, C7, C8, C9 [Part C], and Week 72 for Part E and Cohorts C10 and C11 [Part C])

• Change from Baseline in Hematology parameter: Platelet count (cells per microliter)

  Baseline (Day 1) and up to end of study (Week 78 for Cohorts C1 and C3 [Part C], Week 52 for Part A, Cohorts C2, C4, C5, C6, C7, C8, C9 [Part C], and Week 72 for Part E and Cohorts C10 and C11 [Part C])

• Change from Baseline in Hematology parameters: Reticulocytes (Percentage of reticulocytes)

  Baseline (Day 1) and up to end of study (Week 78 for Cohorts C1 and C3 [Part C], Week 52 for Part A, Cohorts C2, C4, C5, C6, C7, C8, C9 [Part C], and Week 72 for Part E and Cohorts C10 and C11 [Part C])

• Change from Baseline in Hematology parameters: Hematocrit (Proportion of red blood cells in blood)

  Baseline (Day 1) and up to end of study (Week 78 for Cohorts C1 and C3 [Part C], Week 52 for Part A, Cohorts C2, C4, C5, C6, C7, C8, C9 [Part C], and Week 72 for Part E and Cohorts C10 and C11 [Part C])

• Change from Baseline in Hematology parameters: Hgb (grams per deciliter)

  Baseline (Day 1) and up to end of study (Week 78 for Cohorts C1 and C3 [Part C], Week 52 for Part A, Cohorts C2, C4, C5, C6, C7, C8, C9 [Part C], and Week 72 for Part E and Cohorts C10 and C11 [Part C])

• Change from Baseline in Hematology parameter: RBC Count (million cells per microliter)

  Baseline (Day 1) and up to end of study (Week 78 for Cohorts C1 and C3 [Part C], Week 52 for Part A, Cohorts C2, C4, C5, C6, C7, C8, C9 [Part C], and Week 72 for Part E and Cohorts C10 and C11 [Part C])

• Change from Baseline in Hematology parameter: MCV (Femtoliters)

  Baseline (Day 1) and up to end of study (Week 78 for Cohorts C1 and C3 [Part C], Week 52 for Part A, Cohorts C2, C4, C5, C6, C7, C8, C9 [Part C], and Week 72 for Part E and Cohorts C10 and C11 [Part C])

• Change from Baseline in Hematology parameter: MCH (picograms)

  Baseline (Day 1) and up to end of study (Week 78 for Cohorts C1 and C3 [Part C], Week 52 for Part A, Cohorts C2, C4, C5, C6, C7, C8, C9 [Part C], and Week 72 for Part E and Cohorts C10 and C11 [Part C])

• Change from Baseline in Hematology parameters: Differential count of Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils (Giga cells per liter)

  Baseline (Day 1) and up to end of study (Week 78 for Cohorts C1 and C3 [Part C], Week 52 for Part A, Cohorts C2, C4, C5, C6, C7, C8, C9 [Part C], and Week 72 for Part E and Cohorts C10 and C11 [Part C])

• Change from Baseline in Clinical Chemistry parameters: Glucose (fasting), BUN, Creatinine, Sodium, Potassium, Calcium, Direct Bilirubin and Total Bilirubin (milligrams per deciliter)

  Baseline (Day 1) and up to end of study (Week 78 for Cohorts C1 and C3 [Part C], Week 52 for Part A, Cohorts C2, C4, C5, C6, C7, C8, C9 [Part C], and Week 72 for Part E and Cohorts C10 and C11 [Part C])

• Change from Baseline in Clinical Chemistry parameters: AST/SGOT, ALT/ SGPT, ALP and CPK (International Units per liter)

  Baseline (Day 1) and up to end of study (Week 78 for Cohorts C1 and C3 [Part C], Week 52 for Part A, Cohorts C2, C4, C5, C6, C7, C8, C9 [Part C], and Week 72 for Part E and Cohorts C10 and C11 [Part C])

• Change from Baseline in Clinical chemistry parameters: Albumin and Total Protein (Grams per deciliter)

  Baseline (Day 1) and up to end of study (Week 78 for Cohorts C1 and C3 [Part C], Week 52 for Part A, Cohorts C2, C4, C5, C6, C7, C8, C9 [Part C], and Week 72 for Part E and Cohorts C10 and C11 [Part C])

• Number of participants with maximum toxicity grades increase from Baseline in hematology and clinical chemistry

  Up to end of study (Week 78 for Cohorts C1 and C3 [Part C], Week 52 for Part A, Cohorts C2, C4, C5, C6, C7, C8, C9 [Part C], and Week 72 for Part E and Cohorts C10 and C11 [Part C])

Secondary Outcomes (7)

• Dose proportionality of CAB and RPV based on AUC(0-inf)

  Up to end of study (Week 78 for Cohorts C1 and C3 [Part C], Week 52 for Part A, Cohorts C2, C4, C5, C6, C7, C8, C9 [Part C], and Week 72 for Part E and Cohorts C10 and C11 [Part C])

• Dose proportionality of CAB and RPV based on AUC(0-t)

  Up to end of study (Week 78 for Cohorts C1 and C3 [Part C], Week 52 for Part A, Cohorts C2, C4, C5, C6, C7, C8, C9 [Part C], and Week 72 for Part E and Cohorts C10 and C11 [Part C])

• Dose proportionality of CAB and RPV based on Cmax

  Up to end of study (Week 78 for Cohorts C1 and C3 [Part C], Week 52 for Part A, Cohorts C2, C4, C5, C6, C7, C8, C9 [Part C], and Week 72 for Part E and Cohorts C10 and C11 [Part C])

• Dose proportionality of CAB and RPV based on plasma concentration

  Weeks 4, 8, 12 and 24

• Number of participants with maximum post-baseline QTc values compared to baseline by category (to <=450 milliseconds (msec) or no change, to >450 msec to <=480 msec, to >480 msec to <=500 msec, and to >500 msec)

  Up to end of study (Week 78 for Cohorts C1 and C3 [Part C], Week 52 for Part A, Cohorts C2, C4, C5, C6, C7, C8, C9 [Part C], and Week 72 for Part E and Cohorts C10 and C11 [Part C])

Study Arms (3)

Part A: Participants receiving CAB 200 mg/mL with rHuPH20

EXPERIMENTAL

Part A of the study (CAB 200 mg/mL with rHuPh20) has been closed to further enrolment based on preliminary results.

Drug: Cabotegravir 200 mg/mL; Drug: rHuPH20

Part C: Participants receiving CAB >=400 mg/mL or CAB Formulation I or CAB Formulation J

EXPERIMENTAL

Drug: Cabotegravir >=400 mg/mL; Drug: Cabotegravir Formulation I; Drug: CAB Formulation J

Part E: Participants receiving RPV

EXPERIMENTAL

Drug: RPV

Interventions

Cabotegravir 200 mg/mL DRUG

CAB 200 mg/mL will be administered.

Part A: Participants receiving CAB 200 mg/mL with rHuPH20

Cabotegravir >=400 mg/mL DRUG

CAB \>=400 mg/mL will be administered by IM or SC injection.

Part C: Participants receiving CAB >=400 mg/mL or CAB Formulation I or CAB Formulation J

Cabotegravir Formulation I DRUG

CAB Formulation I will be administered by IM injection.

Part C: Participants receiving CAB >=400 mg/mL or CAB Formulation I or CAB Formulation J

CAB Formulation J DRUG

CAB Formulation J will be administered by IM injection.

Part C: Participants receiving CAB >=400 mg/mL or CAB Formulation I or CAB Formulation J

rHuPH20 DRUG

rHuPH20 will be administered.

Part A: Participants receiving CAB 200 mg/mL with rHuPH20

RPV DRUG

RPV will be administered by IM injection.

Part E: Participants receiving RPV

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• At the time of obtaining informed consent, participants age should be greater than or equal to (\>=)18 years and less than or equal to (\<=) 55 years.
• Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
• Body weight \>=40 kilogram (kg) and body mass index (BMI) within the range \>=18 to \<=32 kilogram per meter square (kg/m\^2).
• Participants who are negative on a single test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (approved molecular polymerase chain reaction \[PCR\] laboratory or point of care test), performed on the day of admission. A negative result is required prior to the administration of study intervention on Day 1.
• Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Capable of giving written informed consent.

You may not qualify if:

• Current presence or history of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders.
• Current or chronic history of liver disease or known hepatic or biliary abnormalities.
• History of ongoing or clinically relevant seizure disorder within the previous 2 years, including participants who have required treatment for seizures within this time period.
• Positive SARS-CoV-2 polymerase chain reaction test, having signs and symptoms which in the opinion of the investigator are suggestive of coronavirus disease 2019 (COVID-19) (i.e., fever, cough etc) within 14 days of inpatient admission, or having contact with known COVID-19 positive person/s in the 14 days prior to inpatient admission.
• Human immunodeficiency virus (HIV-1 or HIV-2) infection as indicated by positive antibody/antigen test.
• History of or on-going high-risk behaviors that, in the opinion of the investigator, may put the participant at increased risk for HIV infection including, but not limited to, participants in HIV discordant relationships, or men who report current or prior unprotected anal sex with other men and those reporting prior or current injecting drug use.
• Presence of hepatitis B surface antigen (HBsAg), or positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
• Abnormal blood pressure.
• Evidence of previous myocardial infarction.
• Any conduction abnormality (including but not specific to left or right complete bundle branch block, atrioventricular \[AV\] block \[2nd degree or higher\], Wolff- Parkinson-White \[WPW\] syndrome).
• Any significant arrhythmia which, in the opinion of the investigator or the medical monitor, will interfere with the safety for the individual participant.
• Alanine transaminase (ALT) \>1.5x upper limit of normal (ULN).
• Bilirubin \>1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35 percent \[%\]).
• Estimated Glomerular Filtration Rate (eGFR) \<60 milliliter per minute (mL/min) using the Chronic Kidney Disease
• Improved Prediction Equations (CKD-EPI) Creatinine Equation (2021).

Sponsors & Collaborators

• ViiV Healthcare: lead
• GlaxoSmithKline: collaborator
• Janssen Sciences Ireland Unlimited Company: collaborator

Study Sites (3)

GSK Investigational Site

Orlando, Florida, 32806, United States

COMPLETED

GSK Investigational Site

Las Vegas, Nevada, 89113, United States

RECRUITING

GSK Investigational Site

Austin, Texas, 78744, United States

RECRUITING

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

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  STUDY DIRECTOR

Central Study Contacts

US GSK Clinical Trials Call Center

CONTACT

877-379-3718; GSKClinicalSupportHD@gsk.com

EU GSK Clinical Trials Call Center

CONTACT

+44 (0) 20 89904466; GSKClinicalSupportHD@gsk.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2022
• First Posted: June 14, 2022
• Study Start: June 14, 2022
• Primary Completion (Estimated): June 8, 2027
• Study Completion (Estimated): June 8, 2027
• Last Updated: December 18, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.

Locations

US (3)