Early Access of TMC207 in Patients With Extensively Drug Resistant or Pre-XDR Pulmonary Tuberculosis
Information source: Janssen Infectious Diseases BVBA
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Tuberculosis
Intervention: TMC207 (Drug)
Phase: Phase 3
Status: Temporarily not available
Sponsored by: Janssen Infectious Diseases BVBA Official(s) and/or principal investigator(s): Janssen Infectious Diseases BVBA Clinical Trial, Study Director, Affiliation: Janssen Infectious Diseases BVBA
Summary
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.
Clinical Details
Official title: Early Access of TMC207 in Combination With Other Anti-Tuberculosis (TB) Drugs in Subjects With Extensively Drug Resistant (XDR) or Pre-XDR Pulmonary Tuberculosis
Study design: N/A
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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
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
Locations and Contacts
Vilnius, Lithuania
Arkhangelsk, Russian Federation
Moscow, Russian Federation
Orel, Russian Federation
Saint-Petersburg, Russian Federation
Additional Information
Last updated: June 17, 2015
|