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A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of a Single Suspension Injection of Investigational Capsid Inhibitors Compared to Placebo in Healthy Adults

Primary Purpose

HIV Infections

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
VH4004280
Placebo
VH4011499
Sponsored by
ViiV Healthcare
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring Healthy participants, Human Immunodeficiency Virus (HIV-1), VH4004280, VH4011499, Long-Acting Injection, Single ascending dose

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Participants who are overtly healthy. Participants who are negative on a single test for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) (approved molecular polymerase chain reaction (PCR), point of care test), performed on the day of admission (Day -1). A negative result is required prior to the administration of study intervention on Day 1. Male or female participants of non-childbearing potential. Capable of giving signed informed consent. Exclusion Criteria: History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, neurological or psychiatric disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention or interfering with the interpretation of data. Abnormal blood pressure. Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years. Breast cancer within the past 10 years. Current or chronic history of liver disease or known hepatic or biliary abnormalities. History of sensitivity to any of the study interventions, a history of drug allergy or other allergy that contraindicates their participation. The participant has an underlying skin disease or disorder that would interfere with assessment of injection sites. Participants considered to have insufficient musculature to allow safe capsid inhibitor intramuscular (gluteus medius) administration. History of or on-going high-risk behaviours that may put the participant at increased risk for HIV. Past or intended use of over-the-counter or prescription medication including herbal medications. Current enrollment or recent past participation in another investigational study. Exposure to more than 4 investigational products within 12 months prior to dosing. Alanine transaminase (ALT) ≥1.5x upper limit of normal (ULN), Total bilirubin ≥1.5x ULN (isolated total bilirubin >1.5xULN), and/or estimated creatinine clearance (eGFR) of <60 millilitre per minute (mL/min)/1.73 square meter (m^2). History of or current infection with hepatitis B or hepatitis C. Positive SARS-CoV-2 polymerase chain reaction test, having signs and symptoms, or having contact with known coronavirus disease 2019 (COVID-19) positive person/s in the 14 days prior to inpatient admission. Use of tobacco or nicotine-containing products, regular alcohol consumption and/or regular use of known drugs of abuse. Positive HIV antibody/antigen test. Abnormal electrocardiogram (ECG) parameters. Evidence of previous myocardial infarction, any conduction abnormality, any significant arrhythmia, non-sustained or sustained ventricular tachycardia, and/or sinus pauses (>3 seconds). The participant has a tattoo or other dermatological condition overlying the location of injection or a prior history of silicone implants or fillers (gluteal) which may interfere with interpretation of injection site reactions or administration of study product.

Sites / Locations

  • GSK Investigational SiteRecruiting
  • GSK Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Experimental

Arm Label

Participants Receiving VH4004280

Participants Receiving Placebo

Participants Receiving VH4011499

Arm Description

Outcomes

Primary Outcome Measures

Number of Participants with Adverse Events (AEs) as per Severity
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Severity of Adverse Event will be assessed using Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS). DAIDS grading scale is used to grade the toxicity associated with injection site reactions (ISR) including injection site pain (or tenderness), erythema (or redness), induration (or swelling), and pruritis. The toxicity level is graded from grade 1(lowest toxicity) to 4 (highest toxicity). Higher grade indicates higher toxicity.
Absolute Values of Liver Chemistry Parameters: Total Bilirubin and Direct Bilirubin (micromoles per liter [umol/L])
Change from Baseline in Liver Chemistry Parameters: Total Bilirubin and Direct Bilirubin (umol/L)
Number of Participants with Maximum Toxicity Grade Change from Baseline in Liver Chemistry Parameters: Total Bilirubin, Direct Bilirubin, Alkaline Phosphatase, Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT)
Absolute Values of Liver Chemistry Parameters: Alkaline Phosphatase, Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT) (International Units per liter)
Change from Baseline in Liver Chemistry Parameters: Alkaline Phosphatase, AST, and ALT (International Units per liter)
Number of Participants with Injection Site Reactions (ISR) AE by Grade Using the DAIDS Grading Scale
DAIDS grading scale is used to grade the toxicity associated with injection site reactions (ISR) including injection site pain (or tenderness), erythema (or redness), induration (or swelling), and pruritis. The toxicity level is graded from grade 1(lowest toxicity) to 4 (highest toxicity). Higher grade indicates higher toxicity.
Duration of ISR (Days) AE
Duration of ISR will be assessed as the time up to which a reaction related to injection site event is persistent.
Area Under the Plasma-concentration Time curve from Time Zero to Infinity (AUC0-inf) of VH4004280
Area Under the Plasma-concentration Time curve from Time Zero to Infinity (AUC0-inf) of VH4011499
Maximum Observed Plasma Concentration (Cmax) of VH4004280
Maximum Observed Plasma Concentration (Cmax) of VH4011499
Time of Maximum Observed Plasma Concentration (tmax) of VH4004280
Time of Maximum Observed Plasma Concentration (tmax) of VH4011499
Apparent Terminal Half-life (t1/2) of VH4004280
Apparent Terminal Half-life (t1/2) of VH4011499

Secondary Outcome Measures

Full Information

First Posted
August 21, 2023
Last Updated
September 29, 2023
Sponsor
ViiV Healthcare
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1. Study Identification

Unique Protocol Identification Number
NCT06012136
Brief Title
A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of a Single Suspension Injection of Investigational Capsid Inhibitors Compared to Placebo in Healthy Adults
Official Title
A Phase 1 Double-Blind (Sponsor-unblinded), Placebo-Controlled, Randomized, Single Dose Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of a Parenterally Administered Suspension of Investigational Capsid Inhibitors in Healthy Adults
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 24, 2023 (Actual)
Primary Completion Date
May 4, 2026 (Anticipated)
Study Completion Date
May 4, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ViiV Healthcare

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

Brief Summary
The primary purpose of the study is to investigate safety and tolerability following single ascending subcutaneous (SC) and intramuscular (IM) doses of capsid inhibitors in healthy participants. The study will also describe the pharmacokinetics following single ascending SC and IM doses of capsid inhibitors in healthy participants.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
Healthy participants, Human Immunodeficiency Virus (HIV-1), VH4004280, VH4011499, Long-Acting Injection, Single ascending dose

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
160 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Participants Receiving VH4004280
Arm Type
Experimental
Arm Title
Participants Receiving Placebo
Arm Type
Placebo Comparator
Arm Title
Participants Receiving VH4011499
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
VH4004280
Intervention Description
VH4004280 will be administered.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo will be administered.
Intervention Type
Drug
Intervention Name(s)
VH4011499
Intervention Description
VH4011499 will be administered.
Primary Outcome Measure Information:
Title
Number of Participants with Adverse Events (AEs) as per Severity
Description
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Severity of Adverse Event will be assessed using Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS). DAIDS grading scale is used to grade the toxicity associated with injection site reactions (ISR) including injection site pain (or tenderness), erythema (or redness), induration (or swelling), and pruritis. The toxicity level is graded from grade 1(lowest toxicity) to 4 (highest toxicity). Higher grade indicates higher toxicity.
Time Frame
Up to Week 52
Title
Absolute Values of Liver Chemistry Parameters: Total Bilirubin and Direct Bilirubin (micromoles per liter [umol/L])
Time Frame
Up to Week 52
Title
Change from Baseline in Liver Chemistry Parameters: Total Bilirubin and Direct Bilirubin (umol/L)
Time Frame
Baseline (Prior to Day 1) and up to Week 52
Title
Number of Participants with Maximum Toxicity Grade Change from Baseline in Liver Chemistry Parameters: Total Bilirubin, Direct Bilirubin, Alkaline Phosphatase, Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT)
Time Frame
Up to Week 52
Title
Absolute Values of Liver Chemistry Parameters: Alkaline Phosphatase, Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT) (International Units per liter)
Time Frame
Up to Week 52
Title
Change from Baseline in Liver Chemistry Parameters: Alkaline Phosphatase, AST, and ALT (International Units per liter)
Time Frame
Baseline (Prior to Day 1) and up to Week 52
Title
Number of Participants with Injection Site Reactions (ISR) AE by Grade Using the DAIDS Grading Scale
Description
DAIDS grading scale is used to grade the toxicity associated with injection site reactions (ISR) including injection site pain (or tenderness), erythema (or redness), induration (or swelling), and pruritis. The toxicity level is graded from grade 1(lowest toxicity) to 4 (highest toxicity). Higher grade indicates higher toxicity.
Time Frame
Up to Week 52
Title
Duration of ISR (Days) AE
Description
Duration of ISR will be assessed as the time up to which a reaction related to injection site event is persistent.
Time Frame
Up to Week 52
Title
Area Under the Plasma-concentration Time curve from Time Zero to Infinity (AUC0-inf) of VH4004280
Time Frame
Up to Week 52
Title
Area Under the Plasma-concentration Time curve from Time Zero to Infinity (AUC0-inf) of VH4011499
Time Frame
Up to Week 52
Title
Maximum Observed Plasma Concentration (Cmax) of VH4004280
Time Frame
Up to Week 52
Title
Maximum Observed Plasma Concentration (Cmax) of VH4011499
Time Frame
Up to Week 52
Title
Time of Maximum Observed Plasma Concentration (tmax) of VH4004280
Time Frame
Up to Week 52
Title
Time of Maximum Observed Plasma Concentration (tmax) of VH4011499
Time Frame
Up to Week 52
Title
Apparent Terminal Half-life (t1/2) of VH4004280
Time Frame
Up to Week 52
Title
Apparent Terminal Half-life (t1/2) of VH4011499
Time Frame
Up to Week 52

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Participants who are overtly healthy. Participants who are negative on a single test for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) (approved molecular polymerase chain reaction (PCR), point of care test), performed on the day of admission (Day -1). A negative result is required prior to the administration of study intervention on Day 1. Male or female participants of non-childbearing potential. Capable of giving signed informed consent. Exclusion Criteria: History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, neurological or psychiatric disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention or interfering with the interpretation of data. Abnormal blood pressure. Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years. Breast cancer within the past 10 years. Current or chronic history of liver disease or known hepatic or biliary abnormalities. History of sensitivity to any of the study interventions, a history of drug allergy or other allergy that contraindicates their participation. The participant has an underlying skin disease or disorder that would interfere with assessment of injection sites. Participants considered to have insufficient musculature to allow safe capsid inhibitor intramuscular (gluteus medius) administration. History of or on-going high-risk behaviours that may put the participant at increased risk for HIV. Past or intended use of over-the-counter or prescription medication including herbal medications. Current enrollment or recent past participation in another investigational study. Exposure to more than 4 investigational products within 12 months prior to dosing. Alanine transaminase (ALT) ≥1.5x upper limit of normal (ULN), Total bilirubin ≥1.5x ULN (isolated total bilirubin >1.5xULN), and/or estimated creatinine clearance (eGFR) of <60 millilitre per minute (mL/min)/1.73 square meter (m^2). History of or current infection with hepatitis B or hepatitis C. Positive SARS-CoV-2 polymerase chain reaction test, having signs and symptoms, or having contact with known coronavirus disease 2019 (COVID-19) positive person/s in the 14 days prior to inpatient admission. Use of tobacco or nicotine-containing products, regular alcohol consumption and/or regular use of known drugs of abuse. Positive HIV antibody/antigen test. Abnormal electrocardiogram (ECG) parameters. Evidence of previous myocardial infarction, any conduction abnormality, any significant arrhythmia, non-sustained or sustained ventricular tachycardia, and/or sinus pauses (>3 seconds). The participant has a tattoo or other dermatological condition overlying the location of injection or a prior history of silicone implants or fillers (gluteal) which may interfere with interpretation of injection site reactions or administration of study product.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
US GSK Clinical Trials Call Center
Phone
877-379-3718
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name or Official Title & Degree
EU GSK Clinical Trials Call Center
Phone
+44 (0) 20 89904466
Email
GSKClinicalSupportHD@gsk.com
Facility Information:
Facility Name
GSK Investigational Site
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89113
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
US GSK Clinical Trials Call Center
Phone
877-379-3718
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name & Degree
EU GSK Clinical Trials Call Centre
Phone
+44 (0) 20 8990 4466
Email
GSKClinicalSupportHD@gsk.com
Facility Name
GSK Investigational Site
City
Austin
State/Province
Texas
ZIP/Postal Code
78744
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
US GSK Clinical Trials Call Center
Phone
877-379-3718
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name & Degree
EU GSK Clinical Trials Call Centre
Phone
+44 (0) 20 8990 4466
Email
GSKClinicalSupportHD@gsk.com

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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 URL
https://www.gsk.com/en-gb/innovation/trials/data-transparency/

Learn more about this trial

A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of a Single Suspension Injection of Investigational Capsid Inhibitors Compared to Placebo in Healthy Adults

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