A Clinical Trial of GSK3640254 + Dolutegravir (DTG) in Human Immunodeficiency Virus-1 Infected Treatment-naive Adults (DYNAMIC)

• ClinicalTrials.gov Identifier: NCT04900038
• Recruitment Status: Active, not recruiting
• First Posted: May 25, 2021
• Last Update Posted: January 25, 2023
• Sponsor: ViiV Healthcare
• Collaborator: Syneos Health
• Information provided by (Responsible Party): ViiV Healthcare

Tracking Information

• First Submitted Date: May 19, 2021
• First Posted Date: May 25, 2021
• Last Update Posted Date: January 25, 2023
• Actual Study Start Date: August 18, 2021
• Actual Primary Completion Date: November 22, 2022 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: May 19, 2021): Percentage (%) of participants with plasma HIV-1 ribonucleic acid (RNA) less than(<)50 copies per milliliter (c/mL) at Week 24 using the Food and Drug Administration (FDA) snapshot algorithm [ Time Frame: At Week 24 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 19, 2021)

• Percentage of participants with plasma HIV-1 RNA <50 c/mL at Week 48 using the FDA snapshot algorithm [ Time Frame: At Week 48 ]
• Absolute values of HIV-1 RNA through Weeks 24 and 48 [ Time Frame: Through Weeks 24 and 48 ]
• Change from Baseline in HIV-1 RNA through Weeks 24 and 48 [ Time Frame: Baseline (Day 1), through Weeks 24 and 48 ]
• Absolute values of cluster of differentiation 4+ (CD4+) T-cell counts through Weeks 24 and 48 [ Time Frame: Through Weeks 24 and 48 ]
• Change from Baseline in CD4+ T-cell counts through Weeks 24 and 48 [ Time Frame: Baseline (Day 1), through Weeks 24 and 48 ]
• Number of participants reporting serious adverse events (SAEs), Deaths, adverse events leading to discontinuation (AELD) and adverse events of special interest (AESIs) through Weeks 24 and 48 [ Time Frame: Through Weeks 24 and 48 ]
• Number of participants who develop genotypic resistance through Week 48 [ Time Frame: Up to Week 48 ]
• Number of participants who develop phenotypic resistance through Week 48 [ Time Frame: Up to Week 48 ]
• Trough concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12, 24 and 48 [ Time Frame: At Weeks 2, 4, 8, 12, 24 and 48 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Clinical Trial of GSK3640254 + Dolutegravir (DTG) in Human Immunodeficiency Virus-1 Infected Treatment-naive Adults
• Official Title: A Phase IIb, Randomized, Double-blind, Parallel-group Study to Assess the Efficacy, Safety, Tolerability, and Resistance Profile of GSK3640254 in Combination With Dolutegravir Compared to Dolutegravir Plus Lamivudine in HIV-1 Infected, Treatment-naïve Adults
• Brief Summary: The purpose of this study is to evaluate the efficacy of GSK3640254 + DTG relative to lamivudine (3TC) + DTG in treatment-naïve adult participants living with human immunodeficiency virus (HIV)-1. The participants will be randomized to one of the three doses of blinded GSK3640254 (100, 150, or 200 milligrams [mgs]) or a reference arm of blinded 3TC-each in combination with open label DTG.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

This is a randomized, parallel-group study.

Masking: Double (Participant, Investigator)
Masking Description:

The dose level of GSK3640254 in each of the treatment arms containing GSK3640254 will be blinded to the research participants and all study personnel during the study through the Week 24 primary endpoint.

Primary Purpose: Treatment

• Condition: HIV Infections

Intervention

• Drug: GSK3640254
  GSK3640254 will be available as 25 mg or 100 mg tablets to be administered orally
• Drug: Dolutegravir
  DTG will be available as 50 mg tablets, to be administered orally
• Drug: Lamivudine capsules
  3TC will be available as 300 mg capsules, to be administered orally as a blinded treatment
• Drug: Lamivudine tablets
  3TC will be available as 300 mg tablets, to be administered orally as an unblinded treatment

Study Arms

• Experimental: Blinded GSK3640254 100 mg + unblinded DTG
  Participants will receive blinded GSK3640254 100 mg + unblinded DTG through at least Week 24 (double blind phase). The participants will receive optimal dose of GSK3640254 after the optimal dose has been selected by study 208379. The participants will receive optimal dose of unblinded GSK3640254 and unblinded DTG once both conditions are met: GSK3640254 optimal dose has been selected AND the study has reached Week 24 primary endpoint.
  Interventions:

  • Drug: GSK3640254
  • Drug: Dolutegravir
• Experimental: Blinded GSK3640254 150 mg + unblinded DTG
  Participants will receive blinded GSK3640254 150 mg + unblinded DTG through at least Week 24 (double blind phase). The participants will receive optimal dose of GSK3640254 after the optimal dose has been selected by study 208379. The participants will receive optimal dose of unblinded GSK3640254 and unblinded DTG once both conditions are met: GSK3640254 optimal dose has been selected AND the study has reached Week 24 primary endpoint.
  Interventions:

  • Drug: GSK3640254
  • Drug: Dolutegravir
• Experimental: Blinded GSK3640254 200 mg + unblinded DTG
  Participants will receive blinded GSK3640254 200 mg + unblinded DTG through at least Week 24 (double blind phase). The participants will receive optimal dose of GSK3640254 after the optimal dose has been selected by study 208379. The participants will receive optimal dose of unblinded GSK3640254 and unblinded DTG once both conditions are met: GSK3640254 optimal dose has been selected AND the study has reached Week 24 primary endpoint.
  Interventions:

  • Drug: GSK3640254
  • Drug: Dolutegravir
• Active Comparator: Blinded 3TC 300 mg + unblinded DTG
  Participants will receive blinded 3TC 300 mg capsules + unblinded DTG through at least Week 24 (double blind phase). The participants will receive unblinded 3TC 300 mg tablets + unblinded DTG once both conditions are met: GSK3640254 optimal dose has been selected by study 208379 AND the study has reached Week 24 primary endpoint.
  Interventions:

  • Drug: Dolutegravir
  • Drug: Lamivudine capsules
  • Drug: Lamivudine tablets

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: July 1, 2022): 85
• Original Estimated Enrollment (submitted: May 19, 2021): 80
• Estimated Study Completion Date: June 7, 2023
• Actual Primary Completion Date: November 22, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Treatment-naive, defined as no anti-retrovirals (ARVs) (in combination or monotherapy) received after a known diagnosis of HIV-1 infection.
• Documented HIV infection and Screening plasma HIV-1 RNA greater than or equal to (>=)1000 c/mL.
• Screening CD4+ T-cell count >=250 cells per millimeter^3 (cells/cubic millimeter).
• Body weight >=50.0 kilograms (kg) (110 pounds [lbs.]) for men and >=45.0 kg (99 lbs.) for women and body mass index (BMI) >18.5 kilograms per meter^2 (kg/meter square). Calculations will utilize sex assigned at birth.

Exclusion Criteria:

• Any evidence of an active Centers for Disease Control and Prevention (CDC) Stage 3 disease [CDC, 2014], except cutaneous Kaposi's sarcoma not requiring systemic therapy.
• Presence of primary HIV infection, evidenced by acute retroviral syndrome (example [e.g.], fever, malaise, fatigue, etc.) and/or evidence of recent (within 3 months) documented viremia without antibody production and/or evidence of recent (within 3 months) documented seroconversion.
• Unstable liver disease (as defined by any of the following: presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice or cirrhosis), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment);
• History of ongoing or clinically relevant hepatitis within the previous 6 months.
• Any history of significant underlying psychiatric disorder.
• Any history of major depressive disorder with or without suicidal features, or anxiety disorders, that required medical intervention (pharmacologic or not) such as hospitalization or other inpatient treatment and/or chronic (>6 months) outpatient treatment.
• A pre-existing condition, in the opinion of the Investigator or Medical Monitor, that could interfere with normal gastrointestinal anatomy or motility (e.g., gastroesophageal reflux disease [GERD], gastric ulcers, gastritis, inflammatory bowel disease), hepatic and/or renal function, or with the absorption, metabolism, and/or excretion of the study interventions or render the participant unable to take oral study treatment.
• Familial or personal history of long QT syndrome or sudden cardiac death.
• Active treatment for a viral infection other than HIV-1, such as Hepatitis B, with an agent that is active against HIV-1 (were known to be infected with HIV-1 after treatment for Hepatitis B was completed).
• Participants who require concomitant medications known to be associated with a prolonged corrected QT (QTc) interval.
• Exposure to an experimental drug, human blood product, monoclonal antibody, or vaccine (which does not have emergency, conditional, or standard market authorization) within 28 days prior to the first dose of study treatment.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Canada, France, Germany, Italy, Portugal, Puerto Rico, South Africa, Spain, United States

Administrative Information

• NCT Number: NCT04900038
• Other Study ID Numbers: 212483
• 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

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, a key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the 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 can be granted, when justified, for up to another 12 months.
• URL: http://clinicalstudydatarequest.com

• Current Responsible Party: ViiV Healthcare
• Original Responsible Party: Same as current
• Current Study Sponsor: ViiV Healthcare
• Original Study Sponsor: Same as current
• Collaborators: Syneos Health

Investigators

• Study Director: GSK Clinical Trials; ViiV Healthcare

• PRS Account: ViiV Healthcare
• Verification Date: January 2023