MK-1439A once a day versus ATRIPLA once a day in treatment-naïve HIV-1 infected subjects

• Register: EUCTR
• Last refreshed on: 19 February 2024
• Main ID: EUCTR2014-003382-17-DE
• Date of registration: 11/05/2015
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
• Public title: MK-1439A once a day versus ATRIPLA once a day in treatment-naïve HIV-1 infected subjects
• Scientific title: A Phase III Multicenter, Double-Blind, Randomized, Active Comparator-Controlled Clinical Trial to Evaluate the Safety and Efficacy of MK-1439A Once-Daily Versus ATRIPLA™ Once-Daily in Treatment-Naïve HIV-1 Infected Subjects - MK-1439A versus ATRIPLA in treatment-naïve HIV-1 infected subjects
• Date of first enrolment: 12/08/2015
• Target sample size: 680
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-003382-17
• 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 for 96 weeks (base study), then open-label for additional 192 weeks (study extensions If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes 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, Brazil, Canada, Chile, Colombia, Denmark, Germany, Guatemala, Israel, Korea, Republic of, Mexico, Netherlands, New Zealand, Peru, Portugal, Puerto Rico, Russian Federation, South Africa, Spain, Switzerland, Taiwan, Thailand, United Kingdom, United States

Contacts

• Name: Global Clinical Trials Operations
• Affiliation: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

• Name: Global Clinical Trials Operations
• Affiliation: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1.be at least 18 years of age on the day of signing the informed consent
2.understand the study procedures and voluntarily agree to participate by giving written informed consent (or have a legal representative provide written informed consent if considered acceptable by local regulatory agencies and/or ERCs/IRBs) for the trial. The subject or his/her legal representative (if considered acceptable by local regulatory agencies and/or ERCs/IRBs) may also provide consent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research.
3.be HIV-1 positive as determined by a positive result on an enzyme-immunoassay, have screening plasma HIV-1 RNA (determined by the central laboratory) =1000 copies/mL within 45 days prior to the treatment phase of this study, and have HIV treatment indicated based on physician assessment. Local treatment guidelines should be considered in the decision to initiate therapy.
4.be naïve to antiretroviral therapy (ART) including investigational antiretroviral agents.
5.have the following laboratory values at screening within 45 days prior to the treatment phase of this study: a) Alkaline phosphatase =3.0 x upper limit of normal b)AST (SGOT) and ALT (SGPT) =5.0 x upper limit of normal c) calculated creatinine clearance at the time of screening = 50 mL/min. d)Hemoglobin =9.0 g/dL (if female) or =10.0 g/dL (if male)
6. calculated creatinine clearacne at the time of Screening = 50 mL/min., based on the Cockroft-Gault equation
7.clinically stable with no signs or symptoms of active infection at the time of entry into the study.
8.be highly unlikely to become pregnant or to impregnate a partner.

In order to be eligible for participation in in study extension 1 at the Week 96 visit, the subject must:
9. have completed the Week 96 visit.
10. be considered, in the opinion of the investigator, to have derived benefit from study participation through Week 96.
11. be considered, in the opinion of the investigator, a clinically appropriate candidate for an additional 96 weeks of treatment with MK-1439A following the end of the base study.
12. understand the procedures in study extension 1 and provide written informed consent to enter the study extension, thus continuing for approximately 2 years beyond the base study.

In order to be eligible to continue receiving study treatment in study extension 2 at the Week 192 visit, the subject must:
13. have completed the Week 192 visit.
14. be considered, in the opinion of the investigator, to have derived benefit from MK-1439A by Week 192 of the study.
15. be considered, in the opinion of the investigator, a clinically appropriate candidate for an additional 2 years (additional 96 weeks) of treatment with MK-1439A.
16. understand the procedures in study extension 2 and have provided written informed consent to enter study extension 2, thus continuing until MK-1439A is commercially available once approved in the local country, or for up to approximately 2 years (whichever comes first) beyond study extension 1.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 675
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion criteria:
1.has a history or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of the study or interfere with the subject’s participation for the full duration of the study, such that it is not in the best interest of the subject to participate.
2.is, at the time of signing informed consent, a user of recreational or illicit drugs or has had a recent history of drug or alcohol abuse or dependence. The nature and potential clinical context of the subject's illicit drug use, in relation to their exclusion from this trial, will be at the discretion of the Investigator.
3.has been treated for a viral infection other than HIV-1, such as hepatitis B, with an agent that is active against HIV-1, including, but not limited to, adefovir, tenofovir, entecavir, emtricitabine, or lamivudine.
4.has documented or known resistance to study drugs including MK-1439, efavirenz, emtricitabine, lamivudine, and/or tenofovir, as defined below:
a.Resistance to MK-1439 or efavirenz for the purpose of this study includes the following NNRTI mutations: L100I, K101E, K101P, K103N, K103S, V106A, V106I, V106M, V108I, E138A, E138G, E138K, E138Q, E138R, V179L, Y181C, Y181I, Y181V, Y188C, Y188H, Y188L, G190A, G190S, H221Y, L234I, P225H, F227C, F227L, F227V, M230L, M230I
b.Resistance to emtricitabine, lamivudine and tenofovir includes the following mutations: K65R, M41L, T69S (insertion complex), Q151M, M184I, M184V, L210W, T215F, T215Y, K219E, K219Q, D67N, K70R and K70E.
5.has participated in a study with an investigational compound/device within 30 days prior to signing informed consent or anticipates participating in such a study involving an investigational compound/device during the course of this study.
6.has used systemic immunosuppressive therapy or immune modulators within 30 days prior to treatment in this study or is anticipated to need them during the course of the study.
Note: Short courses of corticosteroids (e.g., as for asthma exacerbation) will be allowed.
7.requires or is anticipated to require any of the prohibited medications noted in the protocol.
8.has significant hypersensitivity or other contraindication to any of the components of the study drugs as determined by the investigator.
9.has a current (active) diagnosis of acute hepatitis due to any cause.
10.has evidence of decompensated liver disease or liver cirrhosis.
11.is pregnant, breastfeeding, or expecting to conceive.
12.is female and is expecting to donate eggs (at any time during the study) or is male and is expecting to donate sperm (at any time during the study).
13.is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or sponsor staff directly involved with this trial.


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: 20.1 Level: LLT Classification code 10068341 Term: HIV-1 infection System Organ Class: 100000004862

Intervention(s)

Product Name: MK-1439A
Product Code: MK-1439A
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: LAMIVUDINE
CAS Number: 134678-17-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
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: doravirine
Other descriptive name: MK-1439
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: ATRIPLA
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: efavirenz
Other descriptive name: EFAVIRENZ
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 600-
INN or Proposed INN: EMTRICITABINE
CAS Number: 143491-57-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
INN or Proposed INN: TENOFOVIR DISOPROXIL FUMARATE
CAS Number: 202138-50-9
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): The primary efficacy endpoint is the proportion of subjects achieving HIV-1 RNA < 50 copies/mL (by the Abbott RealTime HIV-1 Assay) at Week 48. The primary safety endpoint is the proportion of subjects with certain neuropsychiatric adverse events by Week 48 in the following categories: dizziness, sleep disorders and disturbances and altered sensorium.

Secondary Objective: Base Study:
1)Safety and tolerability of MK-1439A q.d. compared to ATRIPLA™q.d. as assessed by review of the accumulated safety data by weeks 48 and 96 AND as measured by the proportion of subjects with neuropsychiatric AEs in the following categories:
•Depression & suicide/self-injury
•Psychosis & psychotic disorders
And events across the categories of dizziness, sleep disorders, altered sensorium AND as measured by time to discontinuation from study due to AE.
2)Effect of MK-1439A q.d. compared to ATRIPLA™q.d. on fasting LDL C and HDL C as measured by the mean change from baseline at Week 48.
3)Immunologic effect of MK-1439A q.d. compared to ATRIPLA™q.d., as measured by change from baseline in CD4 cell count at Weeks 48 and 96.
4)Superior antiretroviral (ARV) activity of MK-1439A q.d. compared to ATRIPLA q.d. as measured by proportion of subjects achieving HIV-1 RNA <50 copies/mL at Weeks 48 AND 96. 5)Evaluate PK of MK-1439 and the PK-PD association

Timepoint(s) of evaluation of this end point: Treatment week 48

Main Objective: Base Study:
1) To evaluate the non-inferior antiretroviral activity of MK-1439A q.d. compared to ATRIPLA q.d. as measured by the proportion of subjects achieving HIV-1 RNA <50 copies/mL (by the Abbott RealTime HIV-1 Assay) at Week 48.
2) To evaluate the safety and tolerability of MK-1439A q.d. compared with ATRIPLA™ q.d. as measured by the proportion of subjects with neuropsychiatric adverse events in the following categories:
-Dizziness
-Sleep disorders and disturbances
-Altered Sensorium

Secondary Outcome(s)

Secondary end point(s): 1.Safety and tolerability by Week 48 and Week 96
2.Fasting LDL-C as measured by the mean change from baseline at Week 48
3.Fasting non-HDL-C as measured by the mean change from baseline at Week 48
4.Proportion of subjects with neuropsychiatric AEs in the following categories by Week 48: depression and suicide/self-injury and psychosis and psychotic disorders.
5.Proportion of subjects with at least one neuropsychiatric AE in any of the 5 categories of: dizziness, sleep disorders and disturbances, altered sensorium, depression and suicide/self-injury, and psychosis and psychotic disorders.
6.Time to discontinuation from study due to an adverse experience
7.Change from baseline in CD4 cell count at Week 48 and Week 96
8.The proportion of subjects achieving HIV-1 RNA
< 50 copies/mL (by the Abbott RealTime HIV-1 Assay) at Week 96
9.The proportion of subjects achieving HIV-1 RNA
< 40 copies/mL (BLoQ) (by the Abbott RealTime HIV-1 Assay) at Week 48 and Week 96
10.PK of MK-1439 and the PK-PD association

Timepoint(s) of evaluation of this end point: Treatment Weeks 48 and 96

Secondary ID(s)

1439A-021

NCT02403674

Source(s) of Monetary Support

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Ethics review

Status: Approved
Approval date: 03/08/2015
Contact: