An open-label, Proof-of-Concept trial in treatment-naïve HIV-1- infected subjects to evaluate the antiviral activity of a single intramuscular dosing of TMC278LA as monotherapy.
- Conditions
- HIV-1MedDRA version: 9.1Level: LLTClassification code 10020192Term: HIV-1
- Registration Number
- EUCTR2008-006009-18-DE
- Lead Sponsor
- Tibotec Pharmaceuticals
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- Not specified
Subjects must meet all of the following inclusion criteria.
1. Male or female subjects, aged 18 to 60 years, extremes included.
2. Documented HIV-1 infection for at least 6 months prior to screening.
3. ICF signed voluntarily before the first trial-related activity.
4. Able to comply with the protocol requirements and having good accessible veins.
5. HIV-1 plasma viral load at screening visit above 5000 HIV-1 RNA copies/mL.
6. CD4 cell count of at least 200 cells/mm3.
7. Subject has not been treated with a therapeutic HIV vaccine within 1 year prior to screening and has never been treated with an ARV drug (including investigational) prior to screening.
8. Subject agrees not to start ARV therapy (ART) before the baseline visit.
9. Subject agrees to start an investigator-selected oral standard-of-care HAART regimen on Day 8 of the trial.
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
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
Subjects must not have any of the following characteristics.
1. Any condition (including but not limited to alcohol and drug use), which, in the opinion of the investigator, could compromise the subject’s safety and adherence to the protocol.
2. Subjects with any active or chronic hepatic disease.
3. Subject has documented acute HIV-1 infection.
4. Pre-existing ARV drug resistance for NRTIs and NNRTIs (to be determined by the Protocol Virologist) based on genotype testing on HIV-1 virus. The following list of NNRTI RAMs was compiled based on the list of IAS-USA NNRTI RAMs10 and other relevant publications:
A098G K103T E138R Y188L F227C
L100I V106A V179D G190A M230I
K101E V106M V179E G190C M230L
K101P V108I Y181C G190E P236L
K101Q E138A Y181I G190Q K238N
K103H E138G Y181V G190S K238T
K103N E138K Y188C G190T Y318F
K103S E138Q Y188H P225H
5. Life expectancy of less than 6 months.
6. Subject has any currently active Acquired Immunodeficiency Syndrome (AIDS) defining illness (Category C conditions according to the Centers for Disease Control [CDC] Classification System for HIV Infection 1993, refer to Addendum 5: HIV-Related Events or Outcomes) with the following exceptions (to be discussed with the Sponsor prior to enrollment):
- Stable, cutaneous Kaposi’s Sarcoma (i.e., no pulmonary or gastrointestinal involvement other than oral lesions) that is unlikely to require any form of systemic therapy during the trial period;
- Wasting syndrome due to HIV infection if, in the investigator’s opinion, is not actively progressive and its treatment does not require hospitalization or compromise the subject’s safety or compliance to adhere to the trial protocol procedures. If the subject is on maintenance therapy (which may include human growth hormone, appetite stimulants and anabolic steroids) for previously diagnosed wasting, he/she may be eligible for the trial only if such treatment is not included in the list of disallowed medications.
Note: Primary or secondary prophylaxis for an AIDS defining illness is allowed in case the medication used is not part of the disallowed medication.
7. Any active clinically significant disease (e.g., pancreatitis, cardiac dysfunction), or findings during screening or medical history or physical examination that, in the investigator’s opinion, would compromise the outcome of the trial.
8. Receipt of any investigational medication or any prophylactic vaccine within 90 days prior to the trial investigational medication administration.
9. Previously demonstrated clinically significant allergy or hypersensitivity (e.g., have a strong family history of rash, or multiple allergies).
10. Vulnerable subjects (e.g., persons kept in detention).
11. Pregnant or breastfeeding female.
12. Non-vasectomized heterosexually active males without the use of effective birth control methods or not willing to continue practicing these birth control methods from screening onwards until the first 30 days after dosing. As of Day 8, the label of HAART should be followed (see Section 5.2.4).
13. Female of childbearing potential without the use of effective birth control methods or not willing to continue practicing these birth control methods from screening onwards until the first 30 days after dosing. As from Day 8, the label of HAART should be followed (see Section 5.2.4).
Note: Hormone-based contraception may not be reliable when taking TMC278LA;
therefore, to be eligible for this trial, women of childbearing potential should either:
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Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of the trial is to determine the antiviral activity of monotherapy over 7 days following 1 single IM dose of 600 mg TMC278LA in treatment-naïve HIV-1 infected subjects.;Secondary Objective: The secondary objectives are:<br>- to determine the safety and (local) tolerability of 1 single IM dosing of 600 mg TMC278LA;<br>- to determine the inflammatory parameters (C-reactive protein, fibrinogen, erythrocyte sedimentation rate, and serum amyloid A), and the liver function parameters (alanine aminotransferase [ALT], aspartate aminotransferase [AST], and bilirubin);<br>- to evaluate the CD4 and CD8 cell counts;<br>- to determine the plasma pharmacokinetics of TMC278 in HIV-1-infected subjects<br>following 1 single IM dosing of 600 mg TMC278LA throughout the trial.;Primary end point(s): Plasma viral load level
- Secondary Outcome Measures
Name Time Method