COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC:

Get the latest research information from NIH: Menu

Pre-Exposure Prophylaxis Using TMC278LA

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01049932
Recruitment Status : Terminated (Trial closed due to additional safety information.)
First Posted : January 15, 2010
Last Update Posted : August 16, 2010
Information provided by:
St Stephens Aids Trust

Brief Summary:

Pre-exposure prophylaxis (PrEP) is an experimental HIV-prevention strategy using antiretroviral (ARV) agents to protect HIV negative individuals from HIV infection.TMC278 is a new drug being developed for this type of HIV treatment. It is hoped that this drug may be used to help prevent HIV transmission in future. A 'long acting' formulation of TMC278 has been developed. Long acting means that the drug will be present in the blood for longer. It is this formulation of the drug that will be investigated in this study. Subjects will receive the drug by injection.

The purpose of this study is to investigate the safety of the drug and how well it is tolerated by the body. The study will look at the levels of the study drug in the subjects blood over the duration of the study.

Condition or disease Intervention/treatment Phase
HIV Infections Drug: TMC278LA Phase 1 Phase 2

Detailed Description:

While for certain diseases, the use of medications by healthy people has been proven to function as prophylaxis, i.e. malaria, it is still unknown whether PrEP can help prevent HIV infection from exposure during sex or injection-drug use.

To address whether PrEP is safe and effective for use in humans, the traditional sequence of drug development steps should be followed as closely as possible.

TMC278 (rilpivirine) is a new investigational non nucleoside reverse transcriptase inhibitor (NNRTI) discovered and in development by Tibotec, a division of Johnson & Johnson. Data from clinical development (Phase IIB) suggest that TMC278 has a similar efficacy and better side-effect profile as compared to other, older, NNRTIs, such as efavirenz. Like TMC125 (etravirine), TMC278 is a diarylpyrimidine (DAPY - a class of molecule that resembles the pyrimidine nucleotides found in DNA, and which have shown potency in inhibiting the activity of HIV reverse transcriptase).

Tibotec is currently investigating TMC278 in two formulations: an oral formulation for HIV treatment and, in early phase, a long acting (LA) injectable formulation for HIV treatment. The latter has also potential application for HIV transmission prevention.

TMC278LA is an innovative drug formulation and its long apparent half life may allow administration of PrEP monthly rather than orally and daily, as for other ARV that are currently studied as PrEP agents.

Therefore, a phase I/II, open-label, prospective, single arm, pharmacokinetic clinical trial in 100 HIV negative subjects (50% of whom will have to be of self-identified African ancestry and 50% females, approximately) is to be conducted. The study will examine whether a monthly dose of TMC278LA not exceeding 600 mg i/m over a time period of approximately six months, with a loading regimen of the first two i/m injections separated by two weeks, is safe and well tolerated by HIV-negative subjects.

Investigation of drug pharmacokinetics in plasma and genital secretions will be also carried out in order to ensure optimal drug exposure during drug administration.

100 evaluable subjects will be enrolled, with approximately 50 of African ancestry, and 50 females. This will provide 50-subject-years of safety data in order to support a later large phase III global efficacy study.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: PrEP TMC278LA: Safety, Tolerability and Pharmacokinetics of TMC278LA in HIV Negative Volunteers
Study Start Date : March 2010
Actual Primary Completion Date : May 2010
Actual Study Completion Date : May 2010

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Drug Information available for: Rilpivirine

Arm Intervention/treatment
Experimental: All subjects
TMC278LA 600mg injected intramuscularly (i/m)
Drug: TMC278LA
TMC278LA 600mg injected intramuscularly (i/m)
Other Name: Rilpivirine

Primary Outcome Measures :
  1. Local or systemic adverse events including local reactions to the IMP, all DAIDS (2004) grade ≥1 adverse events, serious adverse events (including laboratory abnormalities) and suspected unexpected serious adverse reactions (SUSARs) [ Time Frame: 217 ± 10 days ]

Secondary Outcome Measures :
  1. Drug plasma pharmacokinetics following first i/m dose and at steady state [ Time Frame: 217 ± 10 days ]
  2. Male and female genital tract drug concentrations following first i/m dose and at steady state [ Time Frame: 217 ± 10 days ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

Subjects must meet all of the following inclusion criteria within 42 days prior to the baseline visit:

  1. Must understand and sign a written informed consent form, prior to participation in any screening procedures and must comply with all study requirements
  2. Male or non-pregnant, non-lactating females of different ethnic backgrounds
  3. Age between 18 to 50 years, inclusive
  4. Body Mass Index (BMI) of 16 to 35 kg/m2, inclusive
  5. Absence of any significant health problems on the basis of the screening procedures; including medical history, physical examination, vital signs, ECG
  6. Clinically significant laboratory abnormalities
  7. Willing to undergo HIV testing, HIV discussion and receive HIV test results (according to the "UK National Guidelines for HIV Testing 2008",
  8. Women of childbearing potential must be using an adequate method of contraception (diaphragm, intrauterine device, condoms, anatomical sterility in self or partner) to avoid pregnancy throughout the study and for a period of at least four months after the study follow up visit. Oral hormonal methods and implant contraceptives are allowed but only in combination with the additional protection of a barrier method
  9. If sexually active male, willing to use an effective method of contraception such as condoms, anatomical sterility from the day of enrolment until at least four months after the follow up visit
  10. Likely to remain resident in the UK for the duration of the study and follow-up period
  11. Willing to consent to their personal details being entered onto The Over volunteering Prevention Scheme (TOPS) database
  12. Willing to provide photographic identification at each visit.
  13. Registered with a GP in the UK

Exclusion Criteria:

Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.

  1. Any significant acute or chronic medical illness
  2. Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations
  3. Positive blood screen for syphilis, hepatitis A (IgM) B (HBs Ag) and/or C antibodies
  4. Positive blood screen for HIV-1 and/or HIV-2 antibodies
  5. High-risk behaviour for HIV infection which is defined as having one of the following within six months before study day 0 (first dose):

    i. had unprotected vaginal or anal sex with a known HIV infected person or a casual partner ii. engaged in sex work for money or drugs iii. acquired a sexually transmitted disease iv. having a high risk partner either currently or in the previous six months

  6. Clinically relevant alcohol or drug use (positive urine drug screen) or history of alcohol or drug use considered by the Investigator to be sufficient to hinder compliance with treatment, follow-up procedures or evaluation of adverse events
  7. Exposure to any investigational drug or placebo within 30 days of first dose of study drug (additional check to be made on TOPS
  8. History of severe drug allergy that the Investigator thinks may increase the risk of developing an allergic reaction to the study drug
  9. Use of any drug, including over-the-counter medications and herbal preparations, within two weeks prior to first dose of study drug unless approved by the Investigator
  10. Females who are pregnant or lactating
  11. Females of childbearing potential not using effective non-hormonal birth control methods, or not willing to practise these birth control methods for at least four months after the study follow up visit
  12. Males unwilling to use an effective method of contraception such as condoms, anatomical sterility from the day of enrolment until at least four months after the follow up visit

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01049932

Layout table for location information
United Kingdom
Royal Sussex County Hospital
Brighton, Sussex, United Kingdom, BN2 5BE
St. Thomas's Hospital
London, United Kingdom, SE1 7EH
St Stephen's Centre
London, United Kingdom, SW10 9TH
St. Mary's Hospital
London, United Kingdom, W2 1NY
Sponsors and Collaborators
St Stephens Aids Trust
Layout table for investigator information
Principal Investigator: Marta Boffito, Dr St Stephen's AIDS Trust (London)
Principal Investigator: Akil Jackson, Dr St Stephen's AIDS Trust (London)
Principal Investigator: Martin Fisher, Dr Royal Sussex County Hospital, Brighton
Principal Investigator: Alan Winston, Dr St Mary's Hospital, London
Principal Investigator: Julie Fox, Dr St. Thomas's Hospital (London)
Layout table for additonal information
Responsible Party: Dr Marta Boffito, St Stephen's AIDS Trust Identifier: NCT01049932    
Other Study ID Numbers: SSAT 037
EudraCT: 2009-017631-17 ( Other Identifier: European Clinical Trials Database )
First Posted: January 15, 2010    Key Record Dates
Last Update Posted: August 16, 2010
Last Verified: August 2010
Keywords provided by St Stephens Aids Trust:
Human Immunodeficiency Virus (HIV)
HIV Seronegativity
Additional relevant MeSH terms:
Layout table for MeSH terms
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Anti-HIV Agents