- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01464762
Early Access of TMC207 in Patients With Extensively Drug Resistant or Pre-XDR Pulmonary Tuberculosis
November 23, 2017 updated by: Janssen Infectious Diseases BVBA
Early Access of TMC207 in Combination With Other Anti-Tuberculosis (TB) Drugs in Subjects With Extensively Drug Resistant (XDR) or Pre-XDR Pulmonary Tuberculosis
The purpose of this is a study to provide early access of TMC207 to patients with pulmonary infection due to strains of Mycobacterium tuberculosis (M.
tuberculosis) with resistance to isoniazid (INH), rifampin (RMP), and to a fluoroquinolone (FQ) and/or injectable second line tuberculosis (TB) drug (kanamycin, amikacin, or capreomycin) and who are unable/ineligible to participate in any other TMC207 study.
In addition, information on safety and tolerability of TMC207 in combination with anti-TB drugs will be assessed and the results of microbiology assessments which are recommended to be performed during the early access study will be collected.
Study Overview
Detailed Description
TMC207 is being investigated for the treatment of TB.
TB is a contagious bacterial infection caused by M. tuberculosis that commonly affects the lungs, but can also affect other organs.
Treatment of TB is protracted and burdensome and is further complicated by the emergence of multi-drug resistant M. tuberculosis strains.
TMC207 is a diarylquinoline investigational compound that offers a novel mechanism of anti-TB action by specifically inhibiting mycobacterial adenosine triphosphate (ATP)-synthase.
Multi-drug resistant TB (MDR-TB) is defined as infection with a strain of M. tuberculosis that is resistant to both INH and RMP (also known as rifampicin), two important drugs used to treat drug susceptible TB.
Extensively drug-resistant TB (XDR-TB) is defined as MDR-TB with additional resistance to the most important second-line TB drugs, ie, one of the injectables (kanamycin, amikacin, or capreomycin) and fluoroquinolones.
Pre-XDR TB is defined as MDR-TB with additional resistance to either a FQ or an injectable (kanamycin, amikacin, or capreomycin), but not to both a FQ and an injectable.
Patients with either XDR-TB or pre-XDR will be included in this early access study.
Patients who qualify for the study will be provided with a 24-week regimen of TMC207 which will be administered along with their background regimen (BR).
BR drugs will be provided by the site investigator or designated study personnel in accordance with national TB program (NTP) guidelines.
The BR should be constructed with at least 3 anti-tuberculosis drugs to which the patient's infection is known to be susceptible from recent drug susceptibility testing (DST) results (within the previous 6 months) or likely to be susceptible, based on known treatment history.
The selection of the BR, including the number of companion drugs for TMC207, will be the responsibility of the investigator.
At the screening visit, a completed inclusion/exclusion checklist list will be sent to the sponsor or its representative together with the patient's recent smear or culture and DST results (within preceding 6 months) and laboratory safety results to confirm eligibility.
At baseline, a chest X-ray (CXR) will be taken in case no CXR or results of other imaging of the lungs are available within the previous month.
Once treatment has been initiated, patients will be instructed to follow the visit schedule based on routine clinical care.
Recommended visits and assessments should be planned 2, 4, 12, and 24 weeks following initiation of TMC207 in combination with the BR and 4 weeks (Week 28) and every 24 weeks (Weeks 48, 72, 96, and 120) after completion of TMC207 intake during the 96-week follow-up period.
If needed, extra visits and assessments can be planned at the discretion of the investigator in order to best manage the patient's TB treatment.
Patients who are taking clofazimine with TMC207 will require electrocardiogram (ECG) monitoring at mandatory protocol-specified visits.
Serum chemistry (electrolytes) assessment will be performed at every visit in which an ECG is performed.
After their last intake of TMC207, all patients will continue to take their BR under the supervision of their treating physician or local health center/hospital in accordance with NTP guidelines and local multi-drug resistant (MDR) TB treatment practice (i.e., treatment may be extended for reasons of complicated lung disease, etc.).
Patients will be followed up for 96 weeks (2 years) after their last dose of TMC207 to evaluate the microbiological effect (verification of microbiological status [measured locally as per local standard of care; eg, smear, culture, DST] is recommended to be performed every 24 weeks) that TMC207 has provided these patients, as well as to monitor the safety and tolerability of TMC207.
Patients who withdraw early, unless due to withdrawal of informed consent, will be followed for survival/clinical outcome (approximately every 6 months) until the early access study comes to an end in the patients' corresponding country.
Patients can enter the study until TMC207 will be commercially available in the patient's country or can be accessed from another source or until discontinuation of the development program of TMC207.
Study Type
Expanded Access
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Vilnius, Lithuania
-
-
-
-
-
Arkhangelsk, Russian Federation
-
Moscow, Russian Federation
-
Orel, Russian Federation
-
Saint-Petersburg, Russian Federation
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 99 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Confirmed pulmonary XDR or pre-XDR-TB infection with resistance to INH, RMP, and to a FQ and/or injectable second line TB drug (kanamycin, amikacin, or capreomycin). Confirmation should include previous (within the preceding 6 months) smear or culture and drug susceptibility testing (DST) results demonstrating pulmonary TB with an XDR or pre-XDR resistance pattern
- Patient has limited or no treatment options and is unable/ineligible to participate in any other TMC207 study
- Patient will be managed at a medical center that has been certified by the Green Light Committee of the World Health Organization (WHO) Stop TB Partnership, OR, following an assessment of the site confirms that the site meets equivalent standards. Patients must be able to receive at least 3 anti-TB drugs to which the patient's infection is known to be susceptible from recent DST results (within the previous 6 months) or likely to be susceptible, based on known treatment history, per availability in the country
- Patient is medically stable in the opinion of the investigator on the basis of physical examination, and safety examinations performed at screening
- Patients must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the early access study
Exclusion Criteria:
- History of and/or clinically relevant, currently active or underlying gastrointestinal, cardiovascular, nervous system, psychiatric, metabolic, renal, respiratory (other than due to TB), inflammatory, neoplastic, skin, immunological or infectious disease, which is not stable and controlled. If there are clinically relevant, currently active or underlying diseases, they should not compromise the safety of the patient or the ability to participate in the study as judged by the investigator. The investigator is encouraged to discuss concomitant illnesses with the sponsor
- Patients with complicated or severe extra-pulmonary manifestations of TB, including osteoarticular and central nervous system infection - Patients having received TMC207 in a previous study
- Any condition that, in the opinion of the investigator, would compromise the early access study or the well-being of the patient or prevent the patient from meeting or performing protocol requirements
- Current alcohol, barbiturate, amphetamine, recreational or narcotic drug use, which in the investigator's opinion would compromise patient's safety and/or compliance with the protocol procedures
- Patients with any clinically significant electrocardiogram abnormality at screening
- Patients having received medications (within the last 7 days prior to Day 1) that have the potential of prolonging the QT interval
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Registration Dates
First Submitted
October 31, 2011
First Submitted That Met QC Criteria
October 31, 2011
First Posted (Estimate)
November 4, 2011
Study Record Updates
Last Update Posted (Actual)
November 27, 2017
Last Update Submitted That Met QC Criteria
November 23, 2017
Last Verified
November 1, 2017
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Infections
- Respiratory Tract Infections
- Respiratory Tract Diseases
- Lung Diseases
- Bacterial Infections
- Bacterial Infections and Mycoses
- Gram-Positive Bacterial Infections
- Actinomycetales Infections
- Mycobacterium Infections
- Tuberculosis
- Tuberculosis, Pulmonary
- Anti-Infective Agents
- Anti-Bacterial Agents
- Antitubercular Agents
- Bedaquiline
Other Study ID Numbers
- CR017233
- TMC207TBC3001 (Other Identifier: Janssen Infectious Diseases BVBA)
- 2010-021125-12 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Tuberculosis
-
Global Alliance for TB Drug DevelopmentCompletedTuberculosis | Tuberculosis, Pulmonary | Pulmonary Disease | Multi Drug Resistant Tuberculosis | Drug Sensitive Tuberculosis | Drug-resistant Tuberculosis | Mycobacterium Tuberculosis InfectionUnited States
-
Global Alliance for TB Drug DevelopmentCompletedTuberculosis | Tuberculosis, Pulmonary | Pulmonary Disease | Multi Drug Resistant Tuberculosis | Drug Sensitive Tuberculosis | Drug-resistant Tuberculosis | Mycobacterium Tuberculosis InfectionUnited States
-
University Medical Center GroningenCompletedMultidrug-resistant Tuberculosis | Extensively Drug-resistant TuberculosisNetherlands
-
University of Cape TownUniversity of Stellenbosch; University of Cape Town Lung Institute; University... and other collaboratorsCompletedTuberculosis | Multidrug Resistant Tuberculosis | Extensively-drug Resistant TuberculosisSouth Africa
-
Foundation for Innovative New Diagnostics, SwitzerlandInstitute of Tropical Medicine, Belgium; Research Center Borstel; National Institute...CompletedMultidrug-Resistant Tuberculosis | Isoniazid Resistant Pulmonary Tuberculosis | Rifampicin Resistant Tuberculosis | Pulmonary Tuberculoses
-
National Institute of Allergy and Infectious Diseases...CompletedPulmonary Tuberculosis | Multidrug Resistant Tuberculosis | Extensively Drug Resistant TuberculosisKorea, Republic of
-
Universiteit AntwerpenAurum Institute; University of Stellenbosch; University of the Free State; Free...RecruitingDrug-resistant Tuberculosis | Rifampicin Resistant Tuberculosis | Pulmonary Tuberculoses | Multidrug Resistant TuberculosisSouth Africa
-
Assistance Publique - Hôpitaux de ParisCompletedExtrapulmonary Tuberculosis | Lymph Node Tuberculosis | Bone TuberculosisFrance
-
Centers for Disease Control and PreventionBoston University; Pfizer; Columbia University; University of Texas; University of... and other collaboratorsCompletedMulti-Drug Resistant Tuberculosis | Extensively Drug Resistant TuberculosisSouth Africa
-
Wits Health Consortium (Pty) LtdUniversity of Cape Town; Perinatal HIV Research Unit of the University of the... and other collaboratorsActive, not recruitingTuberculosis | Multi Drug Resistant Tuberculosis | Rifampicin Resistant Tuberculosis | Extensively Drug-Resistant Tuberculosis | Pre-XDR-TBSouth Africa
Clinical Trials on TMC207
-
Janssen Infectious Diseases BVBAWithdrawnMulti-drug Resistant TuberculosisChina, Ukraine, Taiwan, Korea, Republic of, Peru, Brazil, Estonia, Latvia, Philippines, Russian Federation, South Africa, Thailand, Turkey, Georgia, Mexico, Cambodia, Ethiopia
-
Tibotec BVBACompleted
-
Janssen Infectious Diseases BVBACompletedTuberculosisChina, Ukraine, Korea, Republic of, Peru, Estonia, Kenya, Latvia, Philippines, Russian Federation, South Africa, Thailand, Turkey
-
Tibotec BVBACompleted
-
Janssen Research & Development, LLCCompletedLeprosy, MultibacillaryBrazil
-
Global Alliance for TB Drug DevelopmentCompletedPulmonary TuberculosisSouth Africa
-
Janssen Research & Development, LLCRecruitingMultidrug-Resistant TuberculosisMozambique, Philippines, Russian Federation, South Africa, Uganda, Ukraine
-
Janssen Infectious Diseases BVBACompletedTuberculosisSouth Africa, Peru, Latvia, Philippines, Russian Federation, Thailand, Brazil, India
-
Tibotec BVBACompletedModerate Hepatic Impairment
-
Janssen Research & Development, LLCCompleted