E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Human Immunodeficiency Virus-1 infection |
|
E.1.1.1 | Medical condition in easily understood language |
|
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 | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068341 |
E.1.2 | Term | HIV-1 infection |
E.1.2 | System Organ Class | 100000004862 |
|
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 |
To evaluate the non-inferior antiretroviral activity of an immediate switch to MK-1439A on Study Day 1 compared with continuation of a ritonavir-boosted PI based-regimen for 24 weeks, as measured by the proportion of subjects maintaining HIV-1 RNA <50 copies/mL by the Abbott RealTime HIV-1 Assay at Study Week 48 in the Immediate Switch Group and at Study Week 24 in the Delayed Switch Group. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the 1)effect on fasting LDL-C and fasting non-HDL-C of a switch to MK1439A on Day1 compared with continuation of a ritonavir-boosted,PI-based regimen for 24wks 2)non-inferior anti-RT activity of an immediate switch to MK1439A on Day1 vs continuation of a ritonavir-boosted PI-based regimen for 24wks,superior anti-RT activity of an immediate switch to MK1439A on Day1 vs. continuation of a ritonavir-boosted PI based-regimen for 24wks 3)anti-RT activity of an immediate switch to MK-1439A on Day1 vs continuation of a ritonavir-boosted PI-based regimen for 24wks 4)immunological effect of an immediate switch to MK1439A on Day1 vs continuation of a ritonavir-boosted,PI-based regimen for 24wks 5)safety and tolerability of an immediate switch to MK-1439A on Day1 vs continuation of a ritonavir-boosted,PI-based regimen for 24wks 6)the PK of MK1439, as a component of MK1439A and the PK/PD association ,if supported by data. |
|
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. |
|
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) for the trial. The subject or his/her legal representative may also provide consent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research.
3. have plasma HIV-1 RNA levels BLoQ (<40 copies/mL by the Abbott RealTime HIV-1 Assay as determined by the central laboratory) at the screening visit.
4. have been receiving antiretroviral therapy with atazanavir/ritonavir, darunavir/ritonavir or lopinavir/ritonavir in combination with 2 NRTIs (and no other ART) continuously with HIV-1 RNA at undetectable levels for ≥ 6 months prior to the screening visit (as measured at ≥ 2 time points) and have no history of prior virologic failure.
5. be receiving his/her first or second PI-based antiretroviral regimen
6. have no history of using any approved or experimental NNRTI for any length of time.
7. have had a genotype prior to starting his/her initial antiretroviral regimen and have no known resistance to any of the study agents (MK-1439, TDF, or lamivudine).
8. be on either no lipid lowering therapy or on a stable dose of lipid lowering therapy at the time of enrollment
9. have the following laboratory values at screening within 30 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) Hemoglobin ≥9.0 g/dL (if female) or ≥10.0 g/dL (if male), d) calculated creatinine clearance at the time of screening ≥ 50 mL/min.
10. be clinically stable with no signs or symptoms of active infection at the time of entry into the study.
11. be highly unlikely to become pregnant or to impregnate a partner.
|
|
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 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, emtricitabine, entecavir, lamivudine or tenofovir.
Note: Subjects may be enrolled if treatment occurred prior to the diagnosis of HIV or in the context of a complete regimen for HIV
4. has documented or known resistance to study drugs including MK-1439, lamivudine, and/or tenofovir, as defined below:
a. Resistance to MK-1439 for the purpose of this study is considered to include the following NNRTI mutations (as single mutations or components of double or triple mutations): L100I, K101E, K101P, K103S, V106A, V106I, V106M, V108I, E138A, E138G, E138K, E138Q, E138R, V179L, Y181I, Y181V, Y188C, Y188H, Y188L, G190S, H221Y, L234I, P225H, F227C, F227L, F227V, M230L, M230I.
b. Resistance to 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.
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 manifested by the presence of or a history of ascites, esophageal or gastric variceal bleeding, hepatic encephalopathy or other signs or symptoms of advanced liver diseases or has liver cirrhosis and a Child-Pugh Class C score or Pugh-Turcotte (CPT) score > 9.
Note: To calculate the CPT score and associated Child-Pugh Class, refer to the
following website: http://www.mdcalc.com/child-pugh-score-for-cirrhosis-mortality
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.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy hypothesis of this study compares the proportion of subjects maintaining HIV-1 RNA <50 copies/mL at Study Week 48 in the Immediate Switch Group with the proportion of subjects maintaining HIV-1 RNA <50 copies/mL at Study Week 24 in the Delayed Switch Group. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Study Week 48 in the Immediate Switch Group and Study Week 24 in the Delayed Switch Group |
|
E.5.2 | Secondary end point(s) |
Secondary and exploratory measurements for efficacy include the proportion of subjects maintaining HIV-1 RNA <40 copies/ mL, change from baseline in CD4 cell counts, time to loss of virologic response (TLVOR), viral resistance for subjects who meet the virologic failure criteria and whose virus can be amplified, PK of MK-1439 and the PK/PD association. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 54 |
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 |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Canada |
Chile |
Colombia |
Denmark |
France |
Germany |
Guatemala |
Israel |
Italy |
Korea, Republic of |
Mexico |
New Zealand |
Peru |
Poland |
Puerto Rico |
Russian Federation |
South Africa |
Spain |
Switzerland |
Taiwan |
United Kingdom |
United States |
|
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
|
Last subject’s last study-related phone call or visit. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
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 | 2 |
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 |