Recruiting
Phase 1

Cabotegravir with Hyaluronidase

Sponsor:

ViiV Healthcare

Code:

NCT05418868

Conditions

HIV Infections

Eligibility Criteria

Sex: All

Age: 18 - 55

Healthy Volunteers: Accepted

Interventions

Cabotegravir 200 mg/mL

Cabotegravir >=400 mg/mL

Cabotegravir Formulation I

CAB Formulation J

rHuPH20

Study Details

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

Study ID

NCT05418868

Start date

Jun 14, 2022

Status verified date

Dec, 2025

Completion date

Jun 8, 2027

Anticipated

Primary completion date

Jun 8, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 55

Healthy Volunteers: Accepted

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • One or more exclusionary values for a screening Electrocardiogram (ECG).
  • 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).
  • Hemoglobin <12.5 gram per deciliter (g/dL) for men and <11 g/dL for women.
  • Positive pre-study drug/alcohol screen.
  • Regular use of tobacco- or nicotine-containing products within 3 months prior to screening; or urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products (e.g., nicotine patches or vaporizing devices).
  • Regular alcohol consumption within 6 months prior to the study defined as an average weekly intake of >14 units for males or >7 units for females.
  • Regular use of known drugs of abuse.
  • Concurrent participation in another clinical trial (except imaging trials); or has participated in a clinical trial and received an investigational product within the following time period prior to the first dosing day in this study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
  • Participation in the study would result in loss of blood or blood products in excess of 500 mL within 56 days.
  • Exposure to more than four (4) new chemical entities within 12 months prior to the first dosing day.
  • History of sensitivity to any of the study interventions (or components thereof), a history of drug allergy or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation, including a known hypersensitivity to hyaluronidases.
  • Current or anticipated need for chronic anti-coagulation therapy.
  • Hereditary coagulation and platelet disorders (e.g., hemophilia or Von Willebrand disease \[VWD\]).
  • Participant has a tattoo overlying the location of injection or an underlying skin disease or condition (e.g., infection, inflammation, dermatitis, eczema, drug rash, drug allergy, psoriasis, food allergy, urticaria) that, in the opinion of the investigator, may interfere with interpretation of injection site reactions or administration of study intervention.
  • Any other clinical condition, behavior or prior therapy that, in the opinion of the investigator, would make the participant unsuitable for the study; unable to comply with dosing requirements; or unable to comply with study visits.
  • Participant who in the investigator's judgment poses a significant suicidality risk. Participant's history of suicidal behavior and/or suicidal ideation should be considered when evaluating for suicide risk.

Study Design

Enrollment

214 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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

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

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

experimental: Part E: Participants receiving RPV

Interventions

Cabotegravir 200 mg/mL

CAB 200 mg/mL will be administered.

Cabotegravir >=400 mg/mL

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

Cabotegravir Formulation I

CAB Formulation I will be administered by IM injection.

CAB Formulation J

CAB Formulation J will be administered by IM injection.

rHuPH20

rHuPH20 will be administered.

RPV

RPV will be administered by IM injection.

Primary outcome measure

  • Maximum observed plasma concentration (Cmax) of CAB and RPV [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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)] [ Time Frame: Up to end of study (Week 72 for Cohort C10 [Part C]) ]
  • Plasma Concentration of CAB and RPV at Week 4 [ Time Frame: Week 4 ]
  • Plasma Concentration of CAB and RPV at Week 8 [ Time Frame: Week 8 ]
  • Plasma Concentration of CAB and RPV at Week 12 [ Time Frame: Week 12 ]
  • Plasma Concentration of CAB and RPV at Week 16 [ Time Frame: Week 16 ]
  • Plasma Concentration of CAB and RPV at Week 24 [ Time Frame: Week 24 ]
  • Plasma Concentration of RPV at Week 32 [ Time Frame: Week 32 ]
  • Plasma Concentration of CAB at Week 36 [ Time Frame: Week 36 ]
  • Plasma Concentration of RPV at Week 40 [ Time Frame: Week 40 ]
  • Plasma Concentration of CAB and RPV at Week 48 [ Time Frame: Week 48 ]
  • Plasma Concentration of CAB [ Time Frame: At weeks 56, 64 and 72 for Cohorts C11 and C10 [Part C] ]
  • Plasma Concentration of RPV at Week 56 [ Time Frame: Week 56 ]
  • Plasma Concentration of RPV at Week 64 [ Time Frame: Week 64 ]
  • Plasma Concentration of RPV at Week 72 [ Time Frame: Week 72 ]
  • Apparent terminal phase half-life (t1/2) of CAB and RPV [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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]) ]

Central Contacts and Locations

Central contacts

US GSK Clinical Trials Call Center

877-379-3718GSKClinicalSupportHD@gsk.com

EU GSK Clinical Trials Call Center

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

Locations

GSK Investigational Site

Recruiting

Las Vegas, Nevada, United States, 89113

Contacts

US GSK Clinical Trials Call Center

877-379-3718GSKClinicalSupportHD@gsk.com

EU GSK Clinical Trials Call Centre

+44 (0) 20 8990 4466GSKClinicalSupportHD@gsk.com

Principal Investigator:

Shawn Searle

GSK Investigational Site

Recruiting

Austin, Texas, United States, 78744

Contacts

US GSK Clinical Trials Call Center

877-379-3718GSKClinicalSupportHD@gsk.com

EU GSK Clinical Trials Call Centre

+44 (0) 20 8990 4466GSKClinicalSupportHD@gsk.com

Principal Investigator:

Katherine Sides

More Information

Sponsor

ViiV Healthcare

Last update posted

Dec 18, 2025

Last verified

Dec, 2025

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by ViiV Healthcare on 2025-12-18.