A study to evaluate the efficacy, safety, and tolerability of dolutegravir plus lamivudine compared to dolutegravir plus tenofovir/emtricitabine in HIV- 1-infected patients that have not been treated yet.

• Register: EUCTR
• Last refreshed on: 13 October 2020
• Main ID: EUCTR2016-000459-28-BE
• Date of registration: 09/06/2016
• Prospective Registration: Yes
• Primary sponsor: ViiV Healthcare UK Limited
• Public title: A study to evaluate the efficacy, safety, and tolerability of dolutegravir plus lamivudine compared to dolutegravir plus tenofovir/emtricitabine in HIV- 1-infected patients that have not been treated yet.
• Scientific title: A Phase III, randomised, double-blind, multicentre, parallel-group, non-inferiority study evaluating the efficacy, safety, and tolerability of dolutegravir plus lamivudine compared to dolutegravir plus tenofovir/emtricitabine in HIV-1-infected treatment-naïve adults - Gemini 2
• Date of first enrolment: 03/08/2016
• Target sample size: 700
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-000459-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: yes; Other trial design description: Double blind Week 1 to 96. Open label week 96 to 148; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Belgium, Canada, France, Germany, Italy, Mexico, Peru, Poland, Portugal, Romania, Russian Federation, South Africa, Spain, Switzerland, Taiwan, Ukraine, United Kingdom, United States

Contacts

• Name: AD PROJECT MGMT
• Affiliation: PPD

• Name: AD PROJECT MGMT
• Affiliation: PPD

Key inclusion & exclusion criteria

Inclusion criteria:
Eligible subjects must:
•be able to understand and comply with protocol requirements, instructions, and restrictions;
•be likely to complete the study as planned;
•be considered appropriate candidates for participation in an investigative clinical trial with oral medication (e.g. no active substance abuse, acute major organ disease, or planned long-term work assignments out of the country).
A subject will be eligible for inclusion in this study only if all of the following criteria apply:
1. HIV-1 infected adults 18 years of age, (or older, if required by local regulations), at the time of signing the informed consent.
2.Screening plasma HIV-1 RNA of 1000 c/mL to <= 100,000 c/mL. If an independent review of accumulated data from other clinical trials investigating the DTG plus 3TC dual regimen is supportive of the DTG plus 3TC treatment regimen, enrolment will be opened to subjects with Screening plasma HIV-1 RNA of 1000 c/mL to <= 500,000 c/mL;
3.Antiretroviral-naïve (defined as <=10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection). Subjects who received HIV post-exposure prophylaxis (PEP) or pre-exposure prophylaxis (PrEP) in the past are allowed as long as the last PEP/PrEP dose was > 1 year from HIV diagnosis or there is documented HIV seronegativity between the last prophylactic dose and the date of HIV diagnosis.
4.Male or female.
A female subject is eligible to participate if she is not pregnant as confirmed by a negative serum human chorionic gonadotrophin (hCG) test at Screening and negative urine test at Baseline), not lactating, and at least one of the following conditions applies:
a.Non-reproductive potential defined as:
•Pre-menopausal females with one of the following:
•Documented tubal ligation
•Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion
•Hysterectomy
•Documented Bilateral Oophorectomy
•Postmenopausal defined as 12 months of spontaneous amenorrhea and =45 years of age [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and oestradiol levels consistent with menopause is confirmatory (refer to laboratory reference ranges for confirmatory levels)]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.
b.Reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) (see Appendix 9, Section 12.9.1) from 30 days prior to the first dose of study medication and until the last dose of study medication and completion of the Follow-up visit.
The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.
All subjects participating in the study should also be counselled on safer sexual practices, including the use and benefit/risk of effective barrier methods (e.g. male condom), and on the risk of HIV transmission to an uninfected partner.
5.Subject or the subject’s legal representative capable of giving signed informed consent as described in Section 10.2 which includes compliance with the requirements and restrictio
Exclusion criteria:
A subject will not be eligible for inclusion in this study if any of the following criteria apply:
1.Women who are breastfeeding or plan to become pregnant or breastfeed during the study; 2.Any evidence of an active Center for Disease Control and Prevention (CDC) Stage 3 disease [CDC, 2014], except cutaneous Kaposi’s sarcoma not requiring systemic therapy and historical or current CD4 cell counts less than 200 cells/mm3. 3.Subjects with severe hepatic impairment (Class C) as determined by Child-Pugh classification; 4.Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones); 5.Evidence of HBV infection based on the results of testing at Screening for HBV surface antigen (HBsAg), HBV core antibody (anti-HBc), HBV surface antibody (anti-HBs or HBsAb), and HBV DNA as follows:
•Subjects positive for HBsAg are excluded;
•Subjects negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and positive for HBV DNA are excluded.
NOTE: Subjects positive for anti-HBc (negative HBsAg status) and positive for anti-HBs (past and/or current evidence) are immune to HBV and are not excluded.
6.Anticipated need for any HCV therapy during the first 48 weeks of the study and for HCV therapy based on interferon or any drugs that have a potential for adverse drug:drug interactions with study treatment throughout the entire study period;
7.Untreated syphilis infection (positive rapid plasma reagin [RPR] at Screening without clear documentation of treatment). Subjects who are at least 14 days post completed treatment are eligible.
8.History or presence of allergy or intolerance to the study drugs or their components or drugs of their class; 9.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; other localised malignancies require agreement between the investigator and the Study Medical Monitor for inclusion of the subject. 10.Subjects who in the investigator’s judgment, poses a significant suicidality risk. Recent history of suicidal behaviour and/or suicidal ideation may be considered as evidence of serious suicide risk.
EXCLUSIONARY TREATMENTS PRIOR TO SCREENING OR DAY 1
11.Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening; 12.Treatment with any of the following agents within 28 days of Screening i.radiation therapy, ii.cytotoxic chemotherapeutic agents, iii.any systemic immune suppressant;
13.Treatment with any agent, except recognised ART as allowed above (inclusion criterion 3.), with documented activity against HIV-1 in vitro within 28 days of first dose of study treatment; 14.Exposure to an experimental drug or experimental vaccine within either 28 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to the first dose of study treatment. 15.Subjects enrolled in France: the subject has participated in any study using an investigational drug during the previous 60 days or 5 half-lives, or twice the duration of the biological effect of the experimental drug or vaccine, whichever is longer, prior to screening for the study or the subject will participate simultane

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Virus Diseases [C02]

Human Immunodeficiency Virus-1 infection
MedDRA version: 19.0 Level: LLT Classification code 10068341 Term: HIV-1 infection System Organ Class: 100000004862

Intervention(s)

Trade Name: Tivicay®
Product Name: Dolutegravir,DTG
Product Code: GSK1349572
Pharmaceutical Form: Tablet
INN or Proposed INN: DOLUTEGRAVIR
CAS Number: 1051375-19-9
Current Sponsor code: GSK1349572
Other descriptive name: DOLUTEGRAVIR
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Trade Name: Epivir
Product Name: Lamivudine, 3TC
Product Code: GR109714
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: LAMIVUDINE
CAS Number: 134678-17-4
Current Sponsor code: GSK3515864
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-

Trade Name: Truvada
Product Name: Truvada
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: TENOFOVIR DISOPROXIL FUMARATE
CAS Number: 202138-50-9
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
INN or Proposed INN: EMTRICITABINE
CAS Number: 143491-57-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Trade Name: Epivir
Product Name: Lamivudine, 3TC
Product Code: GR109714
Pharmaceutical Form: Tablet
INN or Proposed INN: LAMIVUDINE
CAS Number: 134678-17-4
Current Sponsor code: GSK3515864
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-

Trade Name: Truvada
Product Name: Truvada
Product Code: J05AR03
Pharmaceutical Form: Tablet
INN or Proposed INN: TENOFOVIR DISOPROXIL FUMARATE
CAS Number: 202138-50-9
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
INN or Proposed INN: EMTRICITABINE
CAS Number: 143491-57-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

Primary end point(s): Proportion of subjects with plasma HIV-1 RNA <50 copies/mL (c/mL) at Week 48 using the FDA Snapshot algorithm [Missing, Switch or Discontinuation = Failure (MSD=F)] for the intent-to-treat exposed (ITT-E) population

Secondary Objective: -To demonstrate the antiviral activity ofDTG+3TCversusDTG+TDF/FTC at24,96and144weeks; -To evaluate the antiviral activity,immunological effects,and incidence of disease progression(HIV-associated conditions,AIDS and death)ofDTG+3TCcompared toDTG+TDF/FTCover time;-To assess viral resistance in subjects meeting confirmed virologic withdrawal(CVW)criteria;-To evaluate the safety and tolerability ofDTG+TDF/FTCover time;-To evaluate renal biomarkers(in urine and blood)and bone biomarkers(in blood)in subjects treated withDTG+3TC compared to DTG+TDF/FTC; -To evaluate the effects of DTG + 3TC on
fasting lipids compared to DTG +TDF/FTC over time;-To evaluate the effect of patient demographics and baseline characteristics on response toDTG+3TC compared to DTG+TDF/FTC over time; -To assess change in health-related quality-of-life for subjects treated withDTGplus3TCcompared toDTG+TDF/FTC

Timepoint(s) of evaluation of this end point: At Week 48

Main Objective: To demonstrate non-inferior antiviral activity of DTG + 3TC versus DTG + TDF/FTC at 48 weeks in HIV-1-infected, ART-naïve subjects

Secondary Outcome(s)

Secondary end point(s): 1)Proportion of subjects with plasma HIV-1 RNA <50 c/mL using the
FDA Snapshot algorithm (MSD=F) for the ITT-E population
2)Time to viral suppression (HIV-1 RNA <50 c/mL);
3)Absolute values and changes from Baseline in CD4+ cell counts
4)Incidence of disease progression (HIV-associated conditions, AIDS
and death).
5)Incidence of treatment-emergent genotypic and phenotypic resistance
to DTG and 3TC or TDF/FTC in subjects meeting CVW criteria
6)Incidence and severity of adverse events (AEs) and laboratory
abnormalities;
7)Proportion of subjects who discontinue treatment due to AEs
8)Change from Baseline in renal and bone biomarkers
9)Change from Baseline in fasting lipids;
10)The incidence of Grade 2 or greater laboratory abnormalities in
fasting LDL cholesterol
11)Proportion of subjects by patient subgroup(s) (e.g. by age, gender,
Baseline CD4+ cell count) with plasma HIV-1 RNA <50 c/mL using the
Snapshot algorithm for the ITT-E population
12)Change from Baseline in CD4+ cell counts by patient subgroups
13)Change from Baseline in health related quality of life using EQ-5D-5L

Timepoint(s) of evaluation of this end point: 1) Weeks 24, 96 and 144
2)HIV-1 RNA <50 c/mL
3)Weeks 24, 48, 96 and 144;
4)During study when event occurred
5)During study when event occurred
6)During study when event occurred
7)over 24, 48, 96 and 144 weeks
8)Weeks 24, 48, 96 and 144
9) Weeks 24, 48, 96, and 144;
10) Weeks 24, 48, 96, and 144;
11) at Weeks 24, 48, 96 and 144
12) Weeks 24, 48, 96 and 144
13)Weeks 4, 24, 48, 96, and 144 (or Withdrawal from the study)

Secondary ID(s)

2016-000459-28-DE

205543

Source(s) of Monetary Support

ViiV Healthcare UK Limited

Ethics review

Status: Approved
Approval date: 03/08/2016
Contact:

Results

• Results available: Yes
• Date Posted: 13/04/2019
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-000459-28/results