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

Sponsor

ViiV Healthcare (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04900038

Collaborator

Syneos Health (Other)

Enrollment

Locations

Arms

21.6

Anticipated Duration (Months)

1.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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

Study Design

Study Type:

Interventional

Actual Enrollment :

85 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This is a randomized, parallel-group study.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 :

Aug 18, 2021

Anticipated Primary Completion Date :

Dec 19, 2022

Anticipated Study Completion Date :

Jun 7, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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 [At Week 24]

Secondary Outcome Measures

Percentage of participants with plasma HIV-1 RNA <50 c/mL at Week 48 using the FDA snapshot algorithm [At Week 48]
Absolute values of HIV-1 RNA through Weeks 24 and 48 [Through Weeks 24 and 48]
Change from Baseline in HIV-1 RNA through Weeks 24 and 48 [Baseline (Day 1), through Weeks 24 and 48]
Absolute values of cluster of differentiation 4+ (CD4+) T-cell counts through Weeks 24 and 48 [Through Weeks 24 and 48]
Change from Baseline in CD4+ T-cell counts through Weeks 24 and 48 [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 [Through Weeks 24 and 48]
Number of participants who develop genotypic resistance through Week 48 [Up to Week 48]
Number of participants who develop phenotypic resistance through Week 48 [Up to Week 48]
Trough concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12, 24 and 48 [At Weeks 2, 4, 8, 12, 24 and 48]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Bakersfield	California	United States	93301
2	GSK Investigational Site	Palm Springs	California	United States	92262
3	GSK Investigational Site	Denver	Colorado	United States	80246
4	GSK Investigational Site	Washington	District of Columbia	United States	20005
5	GSK Investigational Site	Fort Pierce	Florida	United States	34982
6	GSK Investigational Site	Miami	Florida	United States	33140
7	GSK Investigational Site	Orlando	Florida	United States	32806
8	GSK Investigational Site	West Palm Beach	Florida	United States	33407
9	GSK Investigational Site	Atlanta	Georgia	United States	30308-2012
10	GSK Investigational Site	Augusta	Georgia	United States	30912
11	GSK Investigational Site	Decatur	Georgia	United States	30033
12	GSK Investigational Site	Macon	Georgia	United States	31201
13	GSK Investigational Site	Savannah	Georgia	United States	31401
14	GSK Investigational Site	Kansas City	Missouri	United States	64111
15	GSK Investigational Site	Omaha	Nebraska	United States	68198
16	GSK Investigational Site	Cincinnati	Ohio	United States	45229
17	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires	Argentina	C1425AGC
18	GSK Investigational Site	Ciudad Autónoma de Buenos Aires	Buenos Aires	Argentina	C1405CKC
19	GSK Investigational Site	Buenos Aires		Argentina	C1141ACG
20	GSK Investigational Site	Buenos Aires		Argentina	C1202ABB
21	GSK Investigational Site	Vancouver	British Columbia	Canada	V6Z 2C7
22	GSK Investigational Site	Ottawa	Ontario	Canada	K1H 8L6
23	GSK Investigational Site	Montreal	Quebec	Canada	H2L 4E9
24	GSK Investigational Site	Montreal	Quebec	Canada	H2L 4P9
25	GSK Investigational Site	Montreal	Quebec	Canada	H4A 3J1
26	GSK Investigational Site	Québec		Canada	G1V 4G2
27	GSK Investigational Site	Lyon		France	69004
28	GSK Investigational Site	Marseille		France	13003
29	GSK Investigational Site	Orléans		France	45100
30	GSK Investigational Site	Paris		France	75012
31	GSK Investigational Site	Paris		France	75018
32	GSK Investigational Site	Tourcoing cedex		France	59208
33	GSK Investigational Site	Muenchen	Bayern	Germany	81675
34	GSK Investigational Site	Frankfurt	Hessen	Germany	60596
35	GSK Investigational Site	Koeln	Nordrhein-Westfalen	Germany	50668
36	GSK Investigational Site	Koeln	Nordrhein-Westfalen	Germany	50674
37	GSK Investigational Site	Berlin		Germany	10787
38	GSK Investigational Site	Hamburg		Germany	20146
39	GSK Investigational Site	Rome	Lazio	Italy	00168
40	GSK Investigational Site	Bergamo	Lombardia	Italy	24127
41	GSK Investigational Site	Milano	Lombardia	Italy	20127
42	GSK Investigational Site	Almada		Portugal	2805-267
43	GSK Investigational Site	Aveiro		Portugal	3814-501
44	GSK Investigational Site	Cascais		Portugal	2755-009
45	GSK Investigational Site	Matosinhos		Portugal	4450-113
46	GSK Investigational Site	Porto		Portugal	4200-319
47	GSK Investigational Site	Porto		Portugal	4369-004
48	GSK Investigational Site	Vila Nova de Gaia		Portugal	4434-502
49	GSK Investigational Site	San Juan		Puerto Rico	00909
50	GSK Investigational Site	Durban		South Africa	4001
51	GSK Investigational Site	Durban		South Africa	4091
52	GSK Investigational Site	Johannesburg		South Africa	2113
53	GSK Investigational Site	Johannesburg		South Africa	2196
54	GSK Investigational Site	Parow		South Africa	7505
55	GSK Investigational Site	Vosloorus Ext 2		South Africa	1475
56	GSK Investigational Site	Alicante		Spain	03010
57	GSK Investigational Site	Barcelona		Spain	08025
58	GSK Investigational Site	Barcelona		Spain	08035
59	GSK Investigational Site	Barcelona		Spain	08036
60	GSK Investigational Site	Barcelona		Spain	08907
61	GSK Investigational Site	Barcelona		Spain	8003
62	GSK Investigational Site	Bilbao		Spain	48013
63	GSK Investigational Site	Elche		Spain	03203
64	GSK Investigational Site	La Laguna (Santa Cruz De Tenerife)		Spain	38320
65	GSK Investigational Site	Madrid		Spain	28007
66	GSK Investigational Site	Madrid		Spain	28031
67	GSK Investigational Site	Madrid		Spain	28040
68	GSK Investigational Site	Madrid		Spain	28041
69	GSK Investigational Site	Madrid		Spain	28046
70	GSK Investigational Site	Murcia		Spain	30120
71	GSK Investigational Site	Palma de Mallorca		Spain	07198
72	GSK Investigational Site	San Sebastian De Los Reyes		Spain	28701
73	GSK Investigational Site	Sant Boi de Llobregat		Spain	08830
74	GSK Investigational Site	Sevilla		Spain	41013
75	GSK Investigational Site	Valencia		Spain	46026
76	GSK Investigational Site	Vigo		Spain	36312