E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Human Immunodeficiency Virus type 1 (HIV-1) infection |
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E.1.1.1 | Medical condition in easily understood language |
Human immunodeficiency virus (HIV) is a virus that causes a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections to thrive. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
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 assess the efficacy of three doses of BMS-986001 by determining the proportion of subjects with plasma HIV-1 RNA < 50 c/mL as measured by PCR analyses at
Week 24
• To assess the safety of three doses of BMS-986001 in treatment-naive HIV-1 infected subjects as measured by numbers of subjects with SAEs and numbers of subjects with AEs leading to discontinuations through Week 24, as reported on case report forms |
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E.2.2 | Secondary objectives of the trial |
• To assess the efficacy of BMS-986001 by determining the proportion of subjects with plasma HIV-1 RNA < 50 c/mL as measured by PCR analyses through Week 48 and
96
• To assess the safety of BMS-986001 in treatment-naive HIV-1 infected subjects by measuring numbers of subjects with SAEs and numbers of subjects with AEs leading to discontinuations through Weeks 48 and 96, as reported on case report forms
• To assess the antiretroviral activity of BMS-986001 based on change from baseline in CD4+ T-cell count through Weeks 24, 48, and 96
• To assess the number of subjects with virologic failure who exhibit genotypic drug resistance substitutions in viral RNA through Weeks 24, 48, and 96;
• To assess the steady-state plasma PK of BMS-986001 when co-administered with EFV and 3TC in treatment-naive HIV-1 infected subjects |
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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 |
Protocol AI467003: A Phase IIb Randomized, Controlled, partially Blinded Clinical Trial to Investigate Safety, Efficacy and Dose-response of BMS-986001 in Treatment-naive HIV-1-infected Subjects, Followed by an Open-label Period on the Recommended Dose Pharmacogenetics Blood Sample Amendment Number 01 - Site Specific
Site All |
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E.3 | Principal inclusion criteria |
1) Signed Written Informed Consent:
Freely given informed consent must be obtained from subjects prior to clinical trial participation, including informed consent for any screening procedures conducted to establish subject eligibility for the study.
2) Target Population:
a) Men and women at least 18 years of age, (or minimum age as determined by local regulatory or as legal requirements dictate, whichever is higher),
b) Plasma HIV-1 RNA > 5000 copies/mL,
c) Antiretroviral treatment-naive; defined as no current or previous exposure to > 1 week of an antiretroviral drug,
d) CD4 + T-cell count > 200 cells/mm3.
3) Age and Reproductive Status:
a) Women of childbearing potential (WOCBP) and men must be using at least 2 acceptable methods of contraception, including at least one barrier method, to
avoid pregnancy throughout the study, for up to 12 weeks after the last dose of investigational product in such a manner that the risk of pregnancy is minimized,
b) WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start
of investigational product,
c) Women must not be breastfeeding,
d) Sexually active fertile men must use effective birth control if their partners are WOCBP. |
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E.4 | Principal exclusion criteria |
1) Target Disease Exceptions:
a) History of genotypic and/or phenotypic drug resistance testing showing resistance to EFV, TDF, or 3TC.
b) Screening HIV-1 genotypic drug resistance testing showing resistance to EFV, TDF, or 3TC, as defined by the presence of any in the following:
EFV RT: A98G, L100I, K101E/Q/R/P, K103N, V106M, V108I, V179D, Y181C/I, Y188L, G190S/A/T, P225H, F227L, M230I/L;
TDF RT: M41L, K65R, D67N, K70R/E, T69 insertion, L74V, L210W, Y115F, Q151M, T215Y/F, K219Q/E/N;
3TC RT: M184V/I, K65R.
c) Screening HIV-1 genotypic drug resistance testing showing primary protease inhibitor resistance mutations as defined by the presence of any of the following:
PR: D30N, M46I/L, I47V/A, G48V, I50L, I54M/L, Q58E, T74P, L76V, V82A/F/L/T/S, N83D, I84V, N88S, L90M.
2) Medical History and Concurrent Diseases:
a) Any gastrointestinal disease or surgical procedure that may impact absorption of study drug,
b) Presence of a newly diagnosed HIV-related opportunistic infection (OI) or any medical condition requiring acute therapy at the time of enrollment; suspected primary (acute) HIV infection,
c) History of or current presence of clinically relevant cardiac disease, defined by presence of arrhythmias, ischemic disease, or a conduction abnormality including
2nd/3rd degree atrioventricular block (AVB), or any cardiac abnormality deemed clinically relevant by investigator,
d) Personal or family history of long QT syndrome,
e) History of seizures or other clinically relevant CNS disorders,
f) History of diagnosed and uncontrolled mental illness,
g) History of suicidal ideation or attempt,
h) History of Idiopathic Thrombocytopenia Purpura or clinically relevant diagnosis of thrombocytopenia,
i) Active alcohol or substance use which in the investigator’s opinion is sufficient,
to prevent adequate adherence with study therapy or make participation in the study not in the best interest of the subject.
3) Physical and Laboratory Test Findings:
a) Liver enzymes (ALT/AST) > 3 times the upper limit of normal,
b) Alkaline phosphatase > 5 times the upper limit of normal,
c) Creatinine clearance < 60 cc/min,
d) Hemoglobin < 8.0 g/dL,
e) Platelets < 75,000 cells/mm3,
f) Positive blood screen for HBsAg,
g) Positive blood screen for HCV Ab and HCV RNA,
h) Confirmed QT value > 500 msec at Screening or Day -1,
i) Confirmed QTc value > 470 msec for women and > 450 msec for men at Screening or Day -1,
j) Confirmed PR Interval > 260 msec (severe first degree AV block),
k) Confirmed second or third degree heart block at Screening or Day -1,
4) Allergies and Adverse Drug Reaction,
a) History of allergy to TDF, EFV, or 3TC,
b) History of clinically relevant severe drug reaction (such as anaphylaxis or hepatotoxicity.
5) Other Exclusion Criteria:
a) Prisoners or subjects who are involuntarily incarcerated
b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness,
c) Contraindications to any of the study drugs. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Proportion of subjects with plasma HIV-1 RNA < 50 c/mL as measured by polymerase chain reaction (PCR) analyses at Week 24
• Safety as measured by numbers of subjects with SAEs and numbers of subjects with AEs leading to discontinuations through Week 24, as reported on case report forms. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Timepoint of evaluation of primary end point is Week 24. |
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E.5.2 | Secondary end point(s) |
• Proportion of subjects with plasma HIV-1 RNA < 50 c/mL as measured by polymerase chain reaction (PCR) analyses through Weeks 48 and 96;
• Safety as measured by numbers of subjects with SAEs and numbers of subjects with AEs leading to discontinuations through Weeks 48 and 96, as reported on case report forms;
• Changes from baseline in CD4 + T-cell counts through Weeks 24, 48, and 96;
• Numbers of subjects with virologic failure who exhibit drug resistance genotypic substitutions in viral RNA through Weeks 24, 48, and 96;
• Steady-state plasma PK of BMS-986001 when co-administered with EFV and 3TC.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Timepoints of evaluation of secondat end points are Weeks 24, 48 and 96, as explained in section E.5.2. |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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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 | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
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 |
Argentina |
Australia |
Brazil |
Canada |
Chile |
Colombia |
Mexico |
Peru |
South Africa |
Thailand |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |