E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020192 |
E.1.2 | Term | HIV-1 |
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 |
The primary objective of this trial is to provide early access to TMC125 for treatment-experienced HIV-1 infected subjects who have failed multiple ARV regimens and have limited treatment options with currently approved ARVs. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of this trial is to gather information on the safety and tolerability aspects of TMC125 in combination with other ARVs. Available efficacy data will also be collected. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject or Legal Authorized Representative has voluntarily given informed con-
sent before initiation of trial procedures.
2. Subject has documented HIV-1 infection.
3. Male or female subject over 18 years of age.
4. Subject has limited treatment options due to virological failure or intolerance to
multiple ARV regimens.
5. Subject is at least 3-class experienced (3 classes of licensed oral ARVs: N[t]RTIs,
PIs, NNRTIs).
Note: Subjects with primary NNRTI resistance can be included if they are experienced with at least 2 classes of ARVs (PIs, N[t]RTIs) and meet all the other inclusion criteria.
6. Subject has previously received 2 different PI-based regimens.
7. Subject is unable to use currently approved NNRTIs due to resistance (primary or
acquired) and/or intolerance.
8. Subject, if currently receiving an ARV regimen, is not achieving adequate virologic
suppression on his/her current regimen (defined as a confirmed detectable
plasma VL on the current treatment). |
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E.4 | Principal exclusion criteria |
1. Primary HIV infection.
2. Prior or current participation in DUET trials (TMC125-C206 or TMC125-C216).
3. Any condition which, in the opinion of the investigator, could compromise the sub-
ject’s safety or adherence to the protocol.
4. Use of disallowed concomitant therapy, including disallowed ARVs.
5. Use of non-ARV investigational medications within the 30 days prior to baseline
visit.
6. Use of investigational ARVs, unless stated as an exception in Section 5.3.8.2.2 of
the protocol.
7. Any active clinically significant disease (e.g., cardiac dysfunction, pancreatitis,
acute viral infection) or findings during screening of medical history or physical
examination that is not either resolved or stabilized for at least 30 days before
the screening phase of the trial.
8. Acute viral hepatitis, including but not restricted to A, B or C.
9. Pregnant or breast-feeding female.
10. Female subject of childbearing potential not using effective non-hormonal birth
control methods or not willing to continue practicing these birth control methods
from screening until the last trial related activity.
Note: Hormone based contraception may not be reliable when taking TMC125; therefore, to be eligible for this trial, women of childbearing potential who may have vaginal intercourse should either:
(1) Use a double barrier method to prevent pregnancy (i.e., use a condom without
spermicide, with either a diaphragm or cervical cap) or
(2) Use hormone based contraceptives in combination with a barrier contraceptive
(i.e., male condom without spermicide, diaphragm or cervical cap or female
condom) or
(3) Use an intrauterine device (IUD) in combination with a barrier contraceptive (i.e.,
male condom without spermicide, diaphragm or cervical cap or female condom) or
Note: The use of an IUD has been associated with an increased rate of sexually
transmitted diseases.
(4) Be non-heterosexually active, practice sexual abstinence or have a vasectomized
partner (confirmed sterile).
Note: Women who are postmenopausal for at least 2 years, women with total
hysterectomy and women with tubal ligation are considered of nonchildbearing
potential.
11. Subjects with the following laboratory abnormalities as defined by a standard-
ized grading scheme based on the Division of AIDS (DAIDS) grading table (up-
dated version from December 2004, see Section 7.2):
- Hemoglobin < 7,4 g/dL (4,5 mmol/L)
- Absolute neutrophil count < 500/mm³ (0,5 x 10 9/l)
- Platelets < 25 000/mm3 (25 000 x 10 9/l)
- Prothrombin time (PT) >1,5 x upper limit of laboratory normal range (ULN)
Note: Subjects on anticoagulant therapy with elevated PT > 1,5 ULN require approval of the sponsor prior to enrollment.
- Alkaline phosphatase > 5 x ULN
- Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) > 5 x ULN
- Bilirubin > 5 x ULN
Note: Subjects with elevated bilirubin > 5xULN assessed as related to a component
of ART therapy may be enrolled with prior approval of the sponsor.
- Lipase > 3 x ULN
- Amylase > 5 x ULN if lipase > 2 x ULN
- Creatinine > 1,8 x ULN
12. Subjects with clinical or laboratory evidence of significantly decreased hepatic
function or decompensation, irrespective of liver enzyme levels.
Note: Subject can be included with prior approval of the sponsor if the elevated
bilirubin (grade 3 or less) is assessed at the time of screening as related to an
administered ARV and not to liver disease.
Note: Subjects co-infected with chronic hepatitis B or C will be allowed to enter the
trial if their condition is judged to be clinically stable. Subjects diagnosed with
acute viral hepatitis at screening will not be allowed in the trial.
13. Previously demonstrated clinically significant allergy or hypersensitivity to any of
the excipients of the investigational medication (TMC125). |
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E.5 End points |
E.5.1 | Primary end point(s) |
The trial is not set up to show a specific statistical hypothesis but to provide TMC125 to ARV experienced HIV-1 infected subjects with limited treatment options. Further objective is to gather information on safety and tolerability aspects of TMC125.
Safety of TMC125 will be summarized in terms of
-mortality
-non-HIV related SAEs
-subject's disposition
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
To provide early access to TMC125 |
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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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 30 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 125 |
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 |
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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 sponsor reserves the right to close an investigational site or terminate the trial at any time for any reason. In case of an early termination of the trial or temporary halt by the sponsor, the IEC/IRB should be notified within 15 calendar days, including a detailed written explanation of the reasons for the termination/halt. |
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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 |