DOMINO: A Dose-Range Finding Clinical Trial Study in Human Immunodeficiency Virus (HIV-1) Infected Treatment-Naive Adults
Study Details
Study Description
Brief Summary
This is a phase 2b, randomized, multicenter, parallel group, partially blind (to GSK3640254 doses [100, 150 and 200 milligrams ]), active controlled clinical trial. It will aim to investigate the safety, efficacy and dose-response of GSK3640254 compared to dolutegravir (DTG), each given in combination with 2 Nucleoside Reverse Transcriptase Inhibitors (NRTIs) (abacavir/lamivudine [ABC/3TC] or emtricitabine/tenofovir alafenamide [FTC/TAF])
Condition or Disease | Intervention/Treatment | Phase |
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Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Blinded GSK3640254 100 mg + GSK3640254 matching placebo + Open Label ABC/3TC or FTC/TAF
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Drug: GSK3640254
GSK3640254 will be available as a 25 mg and 100 mg tablets to be administered via oral route.
Drug: ABC/3TC
ABC/3TC will be available as abacavir 600 mg/lamivudine 300 mg tablet to be administered via oral route.
Drug: FTC/TAF
FTC/TAF will be available as emtricitabine 200 mg/tenofovir alafenamide 25 mg tablet to be administered via oral route.
Drug: Placebo
Placebo matching GSK3640254 will be administered in the form of tablets via oral route.
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Experimental: Blinded GSK3640254 150 mg + Open Label ABC/3TC or FTC/TAF
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Drug: GSK3640254
GSK3640254 will be available as a 25 mg and 100 mg tablets to be administered via oral route.
Drug: ABC/3TC
ABC/3TC will be available as abacavir 600 mg/lamivudine 300 mg tablet to be administered via oral route.
Drug: FTC/TAF
FTC/TAF will be available as emtricitabine 200 mg/tenofovir alafenamide 25 mg tablet to be administered via oral route.
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Experimental: Blinded GSK3640254 200 mg + GSK3640254 matching placebo + Open Label ABC/3TC or FTC/TAF
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Drug: GSK3640254
GSK3640254 will be available as a 25 mg and 100 mg tablets to be administered via oral route.
Drug: ABC/3TC
ABC/3TC will be available as abacavir 600 mg/lamivudine 300 mg tablet to be administered via oral route.
Drug: FTC/TAF
FTC/TAF will be available as emtricitabine 200 mg/tenofovir alafenamide 25 mg tablet to be administered via oral route.
Drug: Placebo
Placebo matching GSK3640254 will be administered in the form of tablets via oral route.
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Active Comparator: Open Label DTG + Open Label ABC/3TC or FTC/TAF
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Drug: ABC/3TC
ABC/3TC will be available as abacavir 600 mg/lamivudine 300 mg tablet to be administered via oral route.
Drug: FTC/TAF
FTC/TAF will be available as emtricitabine 200 mg/tenofovir alafenamide 25 mg tablet to be administered via oral route.
Drug: Dolutegravir
Dolutegravir will be available as a 50 mg tablet to be administered via oral route.
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Outcome Measures
Primary Outcome Measures
- Proportion of participants with plasma HIV-1 ribonucleic acid (RNA) <50 copies per milliliter (c/mL) at Week 24 [At Week 24]
Secondary Outcome Measures
- Proportion of participants with plasma HIV-1 RNA <50 c/mL at Weeks 48 and 96 [At Weeks 48 and 96]
- Absolute values of HIV-1 RNA at Weeks 24, 48 and 96 [At Weeks 24, 48 and 96]
- Change from Baseline in plasma HIV-1 RNA at Weeks 24, 48 and 96 (c/mL) [Baseline and at Weeks 24, 48 and 96]
- Absolute values of Cluster of differentiation 4 plus (CD4+) cell counts at Weeks 24, 48 and 96 [At Weeks 24, 48 and 96]
- Change from Baseline in CD4+ cell counts at Weeks 24, 48 and 96 (Cells per cubic millimeters [cells/mm^3]) [Baseline and at Weeks 24, 48 and 96]
- Number of participants with Adverse events (AEs), serious adverse events (SAEs), Deaths and adverse events (AEs) leading to treatment discontinuation at Weeks 24, 48 and 96 [At Weeks 24, 48 and 96]
- Severity of AEs at Weeks 24, 48 and 96 [At Weeks 24, 48 and 96]
- Number of participants who develop phenotypic and genotypic resistance resistance at Weeks 24, 48 and 96 [At Weeks 24, 48 and 96]
- Maximum observed concentration (Cmax) of GSK3640254 at steady state at Weeks 24 and 48 [At Weeks 24 and 48]
- AUC over the dosing interval (AUC [0-tau]) of GSK3640254 at Weeks 24 and 48 [At Weeks 24 and 48]
- Plasma concentration at the end of the dosing (Ctau) of GSK3640254 at steady state at Weeks 24 and 48 [At Weeks 24 and 48]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Participants must be 18 years of age inclusive, at the time of signing the informed consent.
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Treatment-naive, defined as no anti-retrovirals (ARVs) (in combination or monotherapy) received after the diagnosis of HIV-1 infection (for example [e.g.], use of Pre-exposure prophylaxis [PreP] meets inclusion.
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Documented HIV infection and Screening plasma HIV-1 RNA greater than or equal to (>=)1000 c/mL.
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Screening CD4+ T-cell count >=250 cells/mm^3.
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Antiviral susceptibility to the NRTI backbone selected should be demonstrated
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Body weight >=50.0 kilograms (kg) (110 pounds [lbs]) for men and >=45.0 kg (99 lbs) for women and body mass index (BMI) greater than (>)18.5 kg/meter square (m^2).Calculations will utilize sex assigned at birth
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Participants who are male at birth and participants who are female at birth.
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Participants who are female at birth: Contraceptive use by participant who are female at birth should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• A participant who is female at birth is eligible to participate if they are not pregnant or breastfeeding, and one of the following conditions applies:
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Is a participant of non-childbearing potential (PONCBP)
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Or is a POCBP and using an acceptable contraceptive method during the study intervention period (at a minimum until after the last dose of study intervention).
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Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
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For participants enrolled in France: a participant will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
Exclusion criteria:
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Any evidence of an active Center for Disease Control and Prevention (CDC) Stage 3 disease, except cutaneous Kaposi's sarcoma not requiring systemic therapy.
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Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal or penile intraepithelial neoplasia.
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Presence of primary HIV-1 infection, evidenced by acute retroviral syndrome (e.g., fever, malaise, fatigue) and/or evidence of recent (within 3 months) documented viremia without antibody production and/or evidence of recent (within 3 months) documented seroconversion.
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Known history of liver cirrhosis with or without viral hepatitis co-infection.
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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).
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History of ongoing or clinically relevant hepatitis within the previous 6 months.
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History of drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates their participation.
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Any history of significant underlying psychiatric disorder, in the opinion of the Investigator or ViiV Medical Monitor, including but not limited to schizophrenia, bipolar disorder with or without psychotic symptoms, other psychotic disorders, or schizotypal (personality) disorder or a clinical assessment of suicidality based on the responses on the Columbia-Suicide Severity Rating Scale (eCSSRS).
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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.
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Any pre-existing physical or other psychiatric condition (including alcohol or drug abuse), which, in the opinion of the Investigator or ViiV Medical Monitor (with or without psychiatric evaluation), could interfere with the participant's ability to comply with the dosing schedule and protocol evaluations or which might compromise the safety of the participant.
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A pre-existing condition, in the opinion of the Investigator or ViiV 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 drugs or render the participant unable to take oral study treatment.
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Myocardial infarction in the past 3 months.
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Familial or personal history of long QT syndrome or sudden cardiac death.
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Medical history, current or historical, of significant cardiac arrhythmias or Electrocardiogram (ECG) findings which, in the opinion of the Investigator or ViiV Medical Monitor, will interfere with the safety of the participant.
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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).
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Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening.
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Treatment with any of the following agents within 28 days of Screening: radiation therapy, cytotoxic chemotherapeutic agents, any systemic immune suppressant.
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Participants receiving any protocol-prohibited medication and who are unwilling or unable to switch to an alternate medication.
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Participants who are unwilling to stop any medications as required by the local lab test for Helicobacter (H.) pylori.
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Participants who require concomitant medications known to be associated with a prolonged Corrected QT interval (QTc).
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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.
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Current enrollment or past participation within the last 30 days before signing of consent in any other clinical study involving an investigational study intervention (including an investigational Coronavirus Disease (COVID) vaccine) or any other type of medical research.
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Any evidence of viral resistance based on the NRTI backbone selected.
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Historical evidence (prior to study screening period) of the presence of resistance- associated mutations gag A364V or A364A/V.
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Creatinine Clearance <50 mL/minute.
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Alanine aminotransferase (ALT) >=3 times upper limit of normal (ULN) or ALT >=2 times ULN and total bilirubin >=1.5 times ULN.
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Evidence of Hepatitis B virus (HBV) infection based on the results of testing for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (anti-HBc), Hepatitis B surface antibody (anti-HBs) and reflex HBV deoxyribonucleic acid (DNA) as follows:
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Participants positive for HBsAg are excluded;
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Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and positive for HBV DNA on reflex testing are excluded.
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Positive Hepatitis C antibody test result at Screening and positive on reflex to Hepatitis C RNA.
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Positive test results for H. pylori;
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Known or suspected active COVID-19 infection or contact with an individual with known COVID-19, within 14 days of study enrollment
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Untreated syphilis infection (positive rapid plasma reagin [RPR] at Screening) without documentation of treatment.
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Presence of moderate-to-severe hepatic impairment (Class B or C) as determined by Child-Pugh classification.
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Any acute laboratory abnormality at Screening, which, in the opinion of the investigator or ViiV Medical Monitor, would preclude participation in the study of an investigational compound.
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Urine Drug Screen positive (showing presence of): Amphetamines, Barbiturates, Cocaine, 3,4-Methyl enedioxy methamphetamine (MDMA) or Phencyclidine, or non-prescribed opiates, oxycodone, benzodiazepines, methadone, methamphetamines or tricyclic antidepressants.
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Any clinically relevant Grade 4 laboratory abnormality at Screen, including results for creatine phosphokinase (CPK) and lipid abnormalities that lack a compelling explanation from the Investigator.
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Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 28 days.
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Exposure to more than 4 new investigational drugs or vaccines (exclusive of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) potential indication within 12 months prior to the first dosing day;
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Treatment with radiation therapy or cytotoxic chemotherapeutic agents or any systemic immunosuppressive agent within 30 days of study drug administration or anticipated need for such treatment within the study;
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ECG Heart Rate <50 beats per minute (bpm) or >100 bpm, or QT duration corrected for heart rate by Fridericia's formula (QTcF) >450 milliseconds (msec).
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For Portugal only: HIV-2 infection (either determined by prior testing, medical history, or obtained locally during the Screening window).
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | GSK Investigational Site | Los Angeles | California | United States | 90027 |
2 | GSK Investigational Site | Fort Pierce | Florida | United States | 34982 |
3 | GSK Investigational Site | Orlando | Florida | United States | 32803 |
4 | GSK Investigational Site | Orlando | Florida | United States | 32806 |
5 | GSK Investigational Site | Berkley | Michigan | United States | 48072 |
6 | GSK Investigational Site | Jackson | Mississippi | United States | 39216-4505 |
7 | GSK Investigational Site | Omaha | Nebraska | United States | 68198 |
8 | GSK Investigational Site | Cincinnati | Ohio | United States | 45267-0405 |
9 | GSK Investigational Site | Dallas | Texas | United States | 75246 |
10 | GSK Investigational Site | Ciudad Autonoma de Buenos Aires | Buenos Aires | Argentina | C1128AAF |
11 | GSK Investigational Site | Ciudad Autonoma de Buenos Aires | Buenos Aires | Argentina | C1207AAP |
12 | GSK Investigational Site | Ciudad Autonoma de Buenos Aires | Buenos Aires | Argentina | C1425AGC |
13 | GSK Investigational Site | Ciudad Autonoma de Buenos Aires | Buenos Aires | Argentina | C1425AWK |
14 | GSK Investigational Site | Ciudad Autónoma de Buenos Aires | Buenos Aires | Argentina | C1405CKC |
15 | GSK Investigational Site | Ciudad de Buenos Aires | Buenos Aires | Argentina | C1202ABB |
16 | GSK Investigational Site | Buenos Aires | Argentina | 1141 | |
17 | GSK Investigational Site | San Juan | Argentina | 5400 | |
18 | GSK Investigational Site | Ottawa | Ontario | Canada | K1H 8L6 |
19 | GSK Investigational Site | Toronto | Ontario | Canada | M5B 1W8 |
20 | GSK Investigational Site | Montreal | Quebec | Canada | H2L 4E9 |
21 | GSK Investigational Site | Montreal | Quebec | Canada | H2L 4P9 |
22 | GSK Investigational Site | Montreal | Quebec | Canada | H4A 3J1 |
23 | GSK Investigational Site | Marseille | France | 13003 | |
24 | GSK Investigational Site | Paris | France | 75018 | |
25 | GSK Investigational Site | Tourcoing cedex | France | 59208 | |
26 | GSK Investigational Site | Muenchen | Bayern | Germany | 81675 |
27 | GSK Investigational Site | Bochum | Nordrhein-Westfalen | Germany | 44787 |
28 | GSK Investigational Site | Koeln | Nordrhein-Westfalen | Germany | 50674 |
29 | GSK Investigational Site | Roma | Lazio | Italy | 00149 |
30 | GSK Investigational Site | Milano | Lombardia | Italy | 20127 |
31 | GSK Investigational Site | Milano | Lombardia | Italy | 20157 |
32 | GSK Investigational Site | Torino | Piemonte | Italy | 10149 |
33 | GSK Investigational Site | Brescia | Italy | 25123 | |
34 | GSK Investigational Site | Milano | Italy | 20157 | |
35 | GSK Investigational Site | Almada | Portugal | 2801-951 | |
36 | GSK Investigational Site | Aveiro | Portugal | 3814-501 | |
37 | GSK Investigational Site | Porto | Portugal | 4099-001 | |
38 | GSK Investigational Site | Porto | Portugal | 4200-319 | |
39 | GSK Investigational Site | Kazan | Russian Federation | 420061 | |
40 | GSK Investigational Site | Saint-Petersburg | Russian Federation | 191167 | |
41 | GSK Investigational Site | Samara | Russian Federation | 443029 | |
42 | GSK Investigational Site | Smolensk | Russian Federation | 214006 | |
43 | GSK Investigational Site | St. Petersburg | Russian Federation | 190103 | |
44 | GSK Investigational Site | Johannesburg | Gauteng | South Africa | 2113 |
45 | GSK Investigational Site | Wentworth | KwaZulu- Natal | South Africa | 4052 |
46 | GSK Investigational Site | Observatory, Cape Town | South Africa | 7925 | |
47 | GSK Investigational Site | Vosloorus Ext 2 | South Africa | 1475 | |
48 | GSK Investigational Site | Alicante | Spain | 03010 | |
49 | GSK Investigational Site | Badalona, Barcelona | Spain | 8916 | |
50 | GSK Investigational Site | Barcelona | Spain | 08025 | |
51 | GSK Investigational Site | Barcelona | Spain | 08035 | |
52 | GSK Investigational Site | L'Hospitalet de Llobregat | Spain | 08907 | |
53 | GSK Investigational Site | La Coruña | Spain | 15006 | |
54 | GSK Investigational Site | Madrid | Spain | 28006 | |
55 | GSK Investigational Site | Madrid | Spain | 28034 | |
56 | GSK Investigational Site | Madrid | Spain | 28040 | |
57 | GSK Investigational Site | Madrid | Spain | 28046 | |
58 | GSK Investigational Site | Malaga | Spain | 29010 | |
59 | GSK Investigational Site | Marbella | Spain | 29600 | |
60 | GSK Investigational Site | Murcia | Spain | 30003 | |
61 | GSK Investigational Site | Palma de Mallorca | Spain | 07010 | |
62 | GSK Investigational Site | Sevilla | Spain | 41013 | |
63 | GSK Investigational Site | Sevilla | Spain | 41014 | |
64 | GSK Investigational Site | Valencia | Spain | 46010 | |
65 | GSK Investigational Site | Valencia | Spain | 46014 | |
66 | GSK Investigational Site | Zuerich | Switzerland | 8091 |
Sponsors and Collaborators
- ViiV Healthcare
Investigators
- Study Director: GSK Clinical Trials, ViiV Healthcare
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 208379