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

• ClinicalTrials.gov Identifier: NCT05418868
• Recruitment Status: Recruiting
• First Posted: June 14, 2022
• Last Update Posted: January 8, 2024
• Sponsor: ViiV Healthcare
• Information provided by (Responsible Party): ViiV Healthcare

Tracking Information

• First Submitted Date: June 9, 2022
• First Posted Date: June 14, 2022
• Last Update Posted Date: January 8, 2024
• Actual Study Start Date: June 14, 2022
• Estimated Primary Completion Date: November 11, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 1, 2022)

• Maximum observed plasma concentration (Cmax) of Cabotegravir [ Time Frame: Up to Week 52 ]
• Time of maximum observed plasma concentration (tmax) of Cabotegravir [ Time Frame: Up to Week 52 ]
• Area under the concentration - time curve from time zero to infinity (AUC[0-inf]) of Cabotegravir [ Time Frame: Up to Week 52 ]
• 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 Cabotegravir [ Time Frame: Up to Week 52 ]
• Plasma Concentration of Cabotegravir at Week 4 [ Time Frame: Week 4 ]
• Plasma Concentration of Cabotegravir at Week 8 [ Time Frame: Week 8 ]
• Plasma Concentration of Cabotegravir at Week 12 [ Time Frame: Week 12 ]
• Plasma Concentration of Cabotegravir at Week 24 [ Time Frame: Week 24 ]
• Apparent terminal phase half-life (t1/2) of Cabotegravir [ Time Frame: Up to Week 52 ]
• Apparent long-acting absorption rate constant (KA-LA) of Cabotegravir [ Time Frame: Up to Week 52 ]
• Number of Participants with Non-serious Adverse Events (non-SAEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Week 52 ]
• Number of Participants with AEs by Severity [ Time Frame: Up to Week 52 ]
• Absolute value of Hematology parameter: Platelet count (cells per microliter) [ Time Frame: Up to Week 52 ]
• Absolute values of Hematology parameters: Reticulocytes (Percentage of reticulocytes) [ Time Frame: Up to Week 52 ]
• Absolute values of Hematology parameters: Hematocrit (Proportion of red blood cells in blood) [ Time Frame: Up to Week 52 ]
• Absolute values of Hematology parameters: Hemoglobin (Hgb) (grams per deciliter) [ Time Frame: Up to Week 52 ]
• Absolute value of Hematology parameter: Red Blood Cell Count (RBC) (million cells per microliter) [ Time Frame: Up to Week 52 ]
• Absolute value of Hematology parameter: Mean Corpuscle Volume (MCV) (Femtoliters) [ Time Frame: Up to Week 52 ]
• Absolute value of Hematology parameter: Mean Corpuscle Hemoglobin (MCH) (Picograms) [ Time Frame: Up to Week 52 ]
• Absolute values of Hematology parameters: Differential count of Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils (giga cells per liter) [ Time Frame: Up to Week 52 ]
• 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 Week 52 ]
• Absolute values of Clinical Chemistry parameters: AST/SGOT, ALT/ SGPT, ALP and CPK (International Units per liter) [ Time Frame: Up to Week 52 ]
  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.
• Absolute values of Clinical chemistry parameters: Albumin and Total Protein (Grams per deciliter) [ Time Frame: Up to Week 52 ]
• Change from Baseline in Hematology parameter: Platelet count (cells per microliter) [ Time Frame: Baseline (Day 1) and up to Week 52 ]
• Change from Baseline in Hematology parameters: Reticulocytes (Percentage of reticulocytes) [ Time Frame: Baseline (Day 1) and up to Week 52 ]
• Change from Baseline in Hematology parameters: Hematocrit (Proportion of red blood cells in blood) [ Time Frame: Baseline (Day 1) and up to Week 52 ]
• Change from Baseline in Hematology parameters: Hgb (grams per deciliter) [ Time Frame: Baseline (Day 1) and up to Week 52 ]
• Change from Baseline in Hematology parameter: RBC Count (million cells per microliter) [ Time Frame: Baseline (Day 1) and up to Week 52 ]
• Change from Baseline in Hematology parameter: MCV (Femtoliters) [ Time Frame: Baseline (Day 1) and up to Week 52 ]
• Change from Baseline in Hematology parameter: MCH (picograms) [ Time Frame: Baseline (Day 1) and up to Week 52 ]
• 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 Week 52 ]
• 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 Week 52 ]
• 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 Week 52 ]
• Change from Baseline in Clinical chemistry parameters: Albumin and Total Protein (Grams per deciliter) [ Time Frame: Baseline (Day 1) and up to Week 52 ]
• Number of participants with maximum toxicity grades increase from Baseline in hematology and clinical chemistry [ Time Frame: Up to Week 52 ]

Original Primary Outcome Measures (submitted: June 9, 2022)

• Maximum observed plasma concentration (Cmax) of Cabotegravir [ Time Frame: Up to Week 52 ]
• Time of maximum observed plasma concentration (tmax) of Cabotegravir [ Time Frame: Up to Week 52 ]
• Area under the concentration - time curve from time zero to infinity [AUC(0-inf)] of Cabotegravir [ Time Frame: Up to Week 52 ]
• 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 Cabotegravir [ Time Frame: Up to Week 52 ]
• Plasma Concentration of Cabotegravir at Week 4 [ Time Frame: Week 4 ]
• Plasma Concentration of Cabotegravir at Week 8 [ Time Frame: Week 8 ]
• Plasma Concentration of Cabotegravir at Week 12 [ Time Frame: Week 12 ]
• Plasma Concentration of Cabotegravir at Week 24 [ Time Frame: Week 24 ]
• Apparent terminal phase half-life (t1/2) of Cabotegravir [ Time Frame: Up to Week 52 ]
• Apparent long-acting absorption rate constant (KA-LA) of Cabotegravir [ Time Frame: Up to Week 52 ]
• Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Week 52 ]
• Number of Participants with AEs by Severity [ Time Frame: Up to Week 52 ]
• Absolute value of Haematology parameter: Platelet count (cells per microliter) [ Time Frame: Up to Week 52 ]
• Absolute values of Haematology parameters: Hematocrit and Reticulocytes (percentage) [ Time Frame: Up to Week 52 ]
• Absolute values of Haematology parameters: Haemoglobin (Hgb), albumin and total protein (grams per deciliter) [ Time Frame: Up to Week 52 ]
• Absolute value of Haematology parameter: Red Blood Cell Count (RBC) (million cells per microliter) [ Time Frame: Up to Week 52 ]
• Absolute value of Haematology parameter: Mean Corpuscle Volume (MCV) (cubic microns) [ Time Frame: Up to Week 52 ]
• Absolute value of Haematology parameter: Mean Corpuscle Hemoglobin (MCH) (picograms per cell) [ Time Frame: Up to Week 52 ]
• Absolute values of Haematology parameters: Differential count of Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils (percentage) [ Time Frame: Up to Week 52 ]
• Absolute values of Clinical Chemistry parameters: Glucose (fasting), Blood Urea Nitrogen (BUN), Creatinine, Direct Bilirubin and Total Bilirubin (milligrams per deciliter) [ Time Frame: Up to Week 52 ]
• Absolute values of Clinical Chemistry parameters: Sodium, Potassium, and Calcium (milliequivalents per liter) [ Time Frame: Up to Week 52 ]
• Absolute values of Clinical Chemistry parameters: AST/SGOT, ALT/ SGPT, ALP and CPK (International Units per liter) [ Time Frame: Up to Week 52 ]
  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.
• Absolute values of Coagulation parameters: Prothrombin time (PT) and Partial thromboplastin time (PTT) [ Time Frame: Up to Week 52 ]
• Absolute value of Coagulation parameter: International normalized ratio (INR) [ Time Frame: Up to Week 52 ]
• Change from Baseline in Haematology parameter: Platelet count (cells per microliter) [ Time Frame: Baseline (Day 1) and up to Week 52 ]
• Change from Baseline in Haematology parameters: Hematocrit and Reticulocytes (percentage) [ Time Frame: Baseline (Day 1) and up to Week 52 ]
• Change from Baseline in Haematology parameters: Hgb, albumin and total protein (grams per deciliter) [ Time Frame: Baseline (Day 1) and up to Week 52 ]
• Change from Baseline in Haematology parameter: RBC Count (million cells per microliter) [ Time Frame: Baseline (Day 1) and up to Week 52 ]
• Change from Baseline in Haematology parameter: MCV (cubic microns) [ Time Frame: Baseline (Day 1) and up to Week 52 ]
• Change from Baseline in Haematology parameter: MCH (picograms per cell) [ Time Frame: Baseline (Day 1) and up to Week 52 ]
• Change from Baseline in Haematology parameters: Differential count of Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils (percentage) [ Time Frame: Baseline (Day 1) and up to Week 52 ]
• Change from Baseline in Clinical Chemistry parameters: Glucose (fasting), BUN, Creatinine, Direct Bilirubin and Total Bilirubin (milligrams per deciliter) [ Time Frame: Baseline (Day 1) and up to Week 52 ]
• Change from Baseline in Clinical Chemistry parameters: Sodium, Potassium, and Calcium (milliequivalents per liter) [ Time Frame: Baseline (Day 1) and up to Week 52 ]
• 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 Week 52 ]
• Change from Baseline in Coagulation parameters: PT and PTT [ Time Frame: Baseline (Day 1) and up to Week 52 ]
• Change from Baseline in Coagulation parameters: INR [ Time Frame: Baseline (Day 1) and up to Week 52 ]
• Number of participants with maximum toxicity grades increase from Baseline in haematology, clinical chemistry and coagulation parameters [ Time Frame: Up to Week 52 ]

Current Secondary Outcome Measures (submitted: December 1, 2022)

• Dose proportionality of Cabotegravir based on AUC(0-inf) [ Time Frame: Up to Week 52 ]
• Dose proportionality of Cabotegravir based on AUC(0-t) [ Time Frame: Up to Week 52 ]
• Dose proportionality of Cabotegravir based on Cmax [ Time Frame: Up to Week 52 ]
• Dose proportionality of Cabotegravir based on plasma concentration [ Time Frame: 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) [ Time Frame: Up to Week 52 ]
• Number of participants with maximum post-baseline increase in QTc values compared to baseline based on category (increase <=30 msec, increase of 31-60 msec, and increase of >60 msec) [ Time Frame: Up to Week 52 ]
• Number of participants with worst case post-baseline values relative to potential clinical importance criteria compared to baseline for diastolic blood pressure (DBP), systolic blood pressure (SBP) and pulse rate [ Time Frame: Up to Week 52 ]
  Number of participants with worst case post-baseline values relative to potential clinical importance criteria compared to baseline will be categorized into change to low, change to within range or no change, and change to high.

Original Secondary Outcome Measures (submitted: June 9, 2022)

• Dose proportionality of Cabotegravir based on AUC(0-inf) [ Time Frame: Up to Week 52 ]
• Dose proportionality of Cabotegravir based on AUC(0-t) [ Time Frame: Up to Week 52 ]
• Dose proportionality of Cabotegravir based on Cmax [ Time Frame: Up to Week 52 ]
• Dose proportionality of Cabotegravir based on plasma concentration [ Time Frame: Week 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) [ Time Frame: Up to Week 52 ]
• Number of participants with maximum post-baseline increase in QTc values compared to baseline based on category (increase <=30 msec, increase of 31-60 msec, and increase of >60 msec) [ Time Frame: Up to Week 52 ]
• Number of participants with worst case post-baseline values relative to potential clinical importance criteria compared to baseline for diastolic blood pressure (DBP), systolic blood pressure (SBP) and pulse rate [ Time Frame: Up to Week 52 ]
  Number of participants with worst case post-baseline values relative to potential clinical importance criteria compared to baseline will be categorized into change to low, change to within range or no change, and change to high.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Investigate Pharmacokinetics, Safety and Tolerability of Long-Acting Cabotegravir Plus Recombinant Human Hyaluronidase PH20 in Healthy Adult Participants
• Official Title: A Phase I, Multi-centre, Open-label, Single Dose Escalation Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Long-acting Cabotegravir Co-administered With Recombinant Human Hyaluronidase PH20 (rHuPH20) in Healthy Adult Volunteers
• 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) and CAB 400 mg/mL without rHuPH20 (Part C) and CAB 400 mg/mL with rHuPH20 (Part D). Part A of the study (CAB 200 mg/mL with rHuPh20) has been closed to further enrolment based on preliminary results.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: HIV Infections

Intervention

• Drug: Cabotegravir 200 mg/mL
  CAB 200 mg/mL will be administered.
• Drug: Cabotegravir 400 mg/mL
  CAB 400 mg/mL will be administered.
• Drug: Recombinant human hyaluronidase PH20 (rHuPH20)
  rHuPH20 will be administered.

Study 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.
  Interventions:

  • Drug: Cabotegravir 200 mg/mL
  • Drug: Recombinant human hyaluronidase PH20 (rHuPH20)
• Experimental: Part C: Participants receiving CAB 400 mg/mL
  Intervention: Drug: Cabotegravir 400 mg/mL
• Experimental: Part D: Participants receiving CAB 400 mg/mL with rHuPH20
  Interventions:

  • Drug: Cabotegravir 400 mg/mL
  • Drug: Recombinant human hyaluronidase PH20 (rHuPH20)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 9, 2022): 60
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 12, 2025
• Estimated Primary Completion Date: November 11, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• At the time of obtaining informed consent, participants age should be equal to or greater than (=>)18 years and equal to or less than (=<) 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: US GSK Clinical Trials Call Center; 877-379-3718; GSKClinicalSupportHD@gsk.com

Contact: EU GSK Clinical Trials Call Center; +44 (0) 20 89904466; GSKClinicalSupportHD@gsk.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05418868
• Other Study ID Numbers: 218012
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (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.
• URL: https://www.gsk.com/en-gb/innovation/trials/data-transparency/

• Current Responsible Party: ViiV Healthcare
• Original Responsible Party: Same as current
• Current Study Sponsor: ViiV Healthcare
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: GSK Clinical Trials; ViiV Healthcare

• PRS Account: ViiV Healthcare
• Verification Date: January 2024