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

January 5, 2024 updated by: ViiV Healthcare

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

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.

Study Overview

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

    • Florida
      • Orlando, Florida, United States, 32806
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • James Dale Taylor II
    • Nevada
      • Las Vegas, Nevada, United States, 89113
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Darin Brimhall
    • New Jersey
      • Berlin, New Jersey, United States, 08009
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Michael A Hassman
        • Contact:
        • Contact:
    • Texas
      • Austin, Texas, United States, 78744
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Craig Boyle
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

Yes

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part C: Participants receiving CAB 400 mg/mL
CAB 400 mg/mL will be administered.
Experimental: Part D: Participants receiving CAB 400 mg/mL with rHuPH20
rHuPH20 will be administered.
CAB 400 mg/mL will be administered.
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.
CAB 200 mg/mL will be administered.
rHuPH20 will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum observed plasma concentration (Cmax) of Cabotegravir
Time Frame: Up to Week 52
Up to Week 52
Time of maximum observed plasma concentration (tmax) of Cabotegravir
Time Frame: Up to Week 52
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
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
Up to Week 52
Plasma Concentration of Cabotegravir at Week 4
Time Frame: Week 4
Week 4
Plasma Concentration of Cabotegravir at Week 8
Time Frame: Week 8
Week 8
Plasma Concentration of Cabotegravir at Week 12
Time Frame: Week 12
Week 12
Plasma Concentration of Cabotegravir at Week 24
Time Frame: Week 24
Week 24
Apparent terminal phase half-life (t1/2) of Cabotegravir
Time Frame: Up to Week 52
Up to Week 52
Apparent long-acting absorption rate constant (KA-LA) of Cabotegravir
Time Frame: Up to Week 52
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
Up to Week 52
Number of Participants with AEs by Severity
Time Frame: Up to Week 52
Up to Week 52
Absolute value of Hematology parameter: Platelet count (cells per microliter)
Time Frame: Up to Week 52
Up to Week 52
Absolute values of Hematology parameters: Reticulocytes (Percentage of reticulocytes)
Time Frame: Up to Week 52
Up to Week 52
Absolute values of Hematology parameters: Hematocrit (Proportion of red blood cells in blood)
Time Frame: Up to Week 52
Up to Week 52
Absolute values of Hematology parameters: Hemoglobin (Hgb) (grams per deciliter)
Time Frame: Up to Week 52
Up to Week 52
Absolute value of Hematology parameter: Red Blood Cell Count (RBC) (million cells per microliter)
Time Frame: Up to Week 52
Up to Week 52
Absolute value of Hematology parameter: Mean Corpuscle Volume (MCV) (Femtoliters)
Time Frame: Up to Week 52
Up to Week 52
Absolute value of Hematology parameter: Mean Corpuscle Hemoglobin (MCH) (Picograms)
Time Frame: Up to Week 52
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
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
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.
Up to Week 52
Absolute values of Clinical chemistry parameters: Albumin and Total Protein (Grams per deciliter)
Time Frame: Up to Week 52
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
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
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
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
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
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
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
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
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
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
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
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
Up to Week 52

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose proportionality of Cabotegravir based on AUC(0-inf)
Time Frame: Up to Week 52
Up to Week 52
Dose proportionality of Cabotegravir based on AUC(0-t)
Time Frame: Up to Week 52
Up to Week 52
Dose proportionality of Cabotegravir based on Cmax
Time Frame: Up to Week 52
Up to Week 52
Dose proportionality of Cabotegravir based on plasma concentration
Time Frame: Weeks 4, 8, 12 and 24
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
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
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.
Up to Week 52

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Study Director: GSK Clinical Trials, ViiV Healthcare

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 14, 2022

Primary Completion (Estimated)

November 11, 2025

Study Completion (Estimated)

November 12, 2025

Study Registration Dates

First Submitted

June 9, 2022

First Submitted That Met QC Criteria

June 9, 2022

First Posted (Actual)

June 14, 2022

Study Record Updates

Last Update Posted (Estimated)

January 8, 2024

Last Update Submitted That Met QC Criteria

January 5, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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/

IPD Sharing 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.

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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