E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Human Immunodeficiency Virus-1 infection |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10000807 |
E.1.2 | Term | Acute HIV infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Base study: 1)To evaluate the antiretroviral activity of MK-1439A 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, as assessed by review of the accumulated safety data by Week 48 and Week 96.
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E.2.2 | Secondary objectives of the trial |
Base study: 1)To evaluate the antiretroviral activity of MK-1439A as measured by the proportion of subjects achieving HIV -1 RNA <50 copies/mL at Week 96. 2)To evaluate the antiretroviral activity of MK-1439A as measured by the proportion of subjects achieving HIV -1 RNA below the limit of quantification of the Abbott RealTime HIV-1 Assay (<40 copies/mL) at Week 48 and Week 96. 3) To evaluate the immunologic effect of MK-1439A, as measured by the change from baseline in CD4 cell count at Week 48 and Week 96. 4) To evaluate the antiretroviral activity of MK-1439A as measured by the time-to-loss-of-virologic-response.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Merck will conduct Future Biomedical Research on DNA (blood) specimens collected during this clinical trial. Such research is for biomarker testing to address emergent questions not described elsewhere in the protocol (as part of the main trial) and will only be conducted on specimens from appropriately consented subjects. The objective of collecting specimens for Future Biomedical Research is to explore and identify biomarkers that inform the scientific understanding of diseases and/or their therapeutic treatments. The overarching goal is to use such information to develop safer, more effective drugs, and/or to ensure that subjects receive the correct dose of the correct drug at the correct time. |
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E.3 | Principal 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.Have a screening CD4 cell count ≥100 cells/mm3 (completed by the central laboratory) within 45 days prior to the treatment phase of this study. 5.Be naïve to antiretroviral therapy (ART) including investigational antiretroviral agents. 6.Prior to screening, have documentation of genotype performed confirming the presence of one and only one of the following NNRTI mutations: K103N, Y181C, or G190A. An additional sample must be obtained and analyzed by the central laboratory as a part of the screening process to establish a baseline resistance profile. The results of the central laboratory test results must be available prior to subject enrollment. If, upon receipt of the central laboratory results, a discordance between the local sample drawn prior to screening and central laboratory results is identified, such that exclusion criterion #4 is met using the central laboratory results, the subject should not be enrolled in the study. In addition, if the central laboratory test results do not confirm inclusion criteria 6, the subject should not be enrolled. 7.Have the following laboratory values during the screening period of the trial: Alkaline phosphatase ≤ 3.0 x upper limit of normal; AST (SGOT) and ALT (SGPT) ≤ 5.0 x upper limit of normal; Hg ≥ 9.0 g/dl (if female) or ≥ 10.0 g/dl (if male); have calculated creatinine clearance at the time of screening ≥ 50 mL/min. 8.Be clinically stable with no signs or symptoms of active infection at the time of entry into the study. 9.Be highly unlikely to become pregnant or to impregnate a partner.
Extension study: In order to be eligible for participation in the study extension at the Week 96 visit, the subject must: 1.Have completed the Week 96 visit. 2.Be considered, in the opinion of the investigator, to have derived benefit from study participation through Week 96. 3.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. 4.Understand the procedures in the study extension and provide written informed consent to enter the study extension, thus continuing for approximately 2 years beyond the base study. |
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E.4 | Principal exclusion criteria |
1.Has a history or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of this 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 (MK-1439, lamivudine, and/or tenofovir) as defined below: a)Resistance to MK-1439 for the purpose of this study is considered to include mutant viruses containing any of the following NNRTI-associated mutations: L100I, K101E, K101P, K103S, V106A, V106I, V106M, V108I, E138K, E138A, E138G, E138Q, E138R, V179L, Y181I, Y181V, Y188C, Y188H, Y188L, G190S, H221Y, P225H, F227C, F227V, F227L, M230I and M230L. b)Any double or triple NNRTI mutation that includes mutations from the above in combination with K103N, Y181C, or G190A. c)Resistance to lamivudine or tenofovir for the purpose of this study is considered to include following NRTI-associated mutations: M41L, A62V, K65R, D67N, K70E, K70R, L74V, V75I, F77L, Y115F, F116Y, Q151M, M184I, M184V, L210W. T215F, T215Y, K219E, and K219Q as well as the T69S insertion complex. 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 during the course of the study. 6.Has any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids, TNF antagonists, or other immunosuppressant drugs during the course of the trial. 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 drug 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. 11.Is pregnant, breastfeeding, or expecting to conceive. 12.Is female and 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be the number of subjects achieving HIV -1 RNA <50 copies/mL (by the Abbott RealTime HIV-1 Assay) at Week 48. The primary safety endpoint will be an assessment of the safety and tolerability at Week 48 and at Week 96. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Treatment Week 48 and Week 96. |
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E.5.2 | Secondary end point(s) |
1)The proportion of subjects achieving HIV -1 RNA <50 copies/mL at Week 96. 2)The proportion of subjects achieving HIV -1 RNA below the limit of quantification of the Abbott RealTime HIV-1 Assay (<40 copies/mL) at Week 48 and Week 96. 3)Change from baseline in CD4 cell count at Week 48 and Week 96. 4)Measurement of the time-to-loss-of-virologic-response. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Treatment Week 48 and Week 96. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
France |
Germany |
Italy |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The overall trial ends when the last subject completes the last study-related phone-call or visit, discontinues from the trial or is lost to follow-up. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |