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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04900038
Recruitment Status : Active, not recruiting
First Posted : May 25, 2021
Last Update Posted : November 29, 2022
Sponsor:
Collaborator:
Syneos Health
Information provided by (Responsible Party):
ViiV Healthcare

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.

Condition or disease Intervention/treatment Phase
HIV Infections Drug: GSK3640254 Drug: Dolutegravir Drug: Lamivudine capsules Drug: Lamivudine tablets Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 85 participants
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
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
Actual Study Start Date : August 18, 2021
Estimated Primary Completion Date : December 19, 2022
Estimated Study Completion Date : June 7, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
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.
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

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.
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

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.
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

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.
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




Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. Percentage of participants with plasma HIV-1 RNA <50 c/mL at Week 48 using the FDA snapshot algorithm [ Time Frame: At Week 48 ]
  2. Absolute values of HIV-1 RNA through Weeks 24 and 48 [ Time Frame: Through Weeks 24 and 48 ]
  3. Change from Baseline in HIV-1 RNA through Weeks 24 and 48 [ Time Frame: Baseline (Day 1), through Weeks 24 and 48 ]
  4. Absolute values of cluster of differentiation 4+ (CD4+) T-cell counts through Weeks 24 and 48 [ Time Frame: Through Weeks 24 and 48 ]
  5. Change from Baseline in CD4+ T-cell counts through Weeks 24 and 48 [ Time Frame: Baseline (Day 1), through Weeks 24 and 48 ]
  6. 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 ]
  7. Number of participants who develop genotypic resistance through Week 48 [ Time Frame: Up to Week 48 ]
  8. Number of participants who develop phenotypic resistance through Week 48 [ Time Frame: Up to Week 48 ]
  9. 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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04900038


Locations
Show Show 53 study locations
Sponsors and Collaborators
ViiV Healthcare
Syneos Health
Investigators
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Study Director: GSK Clinical Trials ViiV Healthcare
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Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT04900038    
Other Study ID Numbers: 212483
First Posted: May 25, 2021    Key Record Dates
Last Update Posted: November 29, 2022
Last Verified: November 2022
Individual Participant Data (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
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by ViiV Healthcare:
Human immunodeficiency virus-1
GSK3640254
Dolutegravir
Lamivudine
Treatment-naive
Additional relevant MeSH terms:
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HIV Infections
Blood-Borne Infections
Communicable Diseases
Infections
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Lamivudine
Dolutegravir
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Anti-HIV Agents
Anti-Retroviral Agents
HIV Integrase Inhibitors
Integrase Inhibitors