Clofazimine treatment of multidrug-resistant tuberculosis (MDRTB)

• Register: EUCTR
• Last refreshed on: 16 January 2017
• Main ID: EUCTR2015-004440-19-LT
• Date of registration: 31/12/2015
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: Clofazimine treatment of multidrug-resistant tuberculosis (MDRTB)
• Scientific title: A 30-month multicenter, phase 2b/3, randomized, open label trial to evaluate the efficacy and safety of clofazimine administered orally in addition to background regimen compared to background regimen alone in the treatment of patients with multidrug-resistant pulmonary tuberculosis
• Date of first enrolment: 11/02/2016
• Target sample size: 380
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-004440-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Background regimen according to local guidelines, provided by national tuberculosis program Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Kenya, Latvia, Lithuania, Peru, Philippines, Russian Federation, South Africa, Thailand

Contacts

• Name: Clinical Trial Information Desk
• Affiliation: Novartis Pharma Services Inc. Representative Office

• Name: Clinical Trial Information Desk
• Affiliation: Novartis Pharma Services Inc. Representative Office

Key inclusion & exclusion criteria

Inclusion criteria:
Patients who fulfill the following criteria are eligible for inclusion in this study:
1. Is willing and able to give informed consent/assent
2. Males and females aged 14 to 70 years
3. Microbiology results: GeneXpert MTB/RIF positive for rifampin resistance AND line probe assay results showing susceptibility to fluoroquinolones and aminoglycosides OR DST results demonstrating rifampin resistance within the preceding 90 days AND line probe assay results showing susceptibility to fluoroquinolones and aminoglycosides
4. Chest X-ray compatible with pulmonary TB such as cavitary lesions, apical infiltrates, hilar lymphadenopathy, new infiltrates.
5. Willing to have a HIV test and initiate therapy with ART if test is positive.
6. Patients who are already receiving ART are eligible for enrollment.
7. Agrees to use effective contraception other than hormonal contraception alone during treatment phase if a pre-menopausal woman
8. Has an identifiable address and expects to remain in the area for the duration of the study.
9. Is willing to adhere to the follow-up schedule and to study procedures
Are the trial subjects under 18? yes
Number of subjects for this age range: 50
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 280
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion criteria:
1. Currently taking part in another trial of a medicinal product
2. History of hypersensitivity to Lamprene or one of its excipients
3. Prior or current treatment of TB with clofazimine, bedaquiline, or delamanid
4. History or current diagnosis of clinically significant ECG abnormalities that pose a safety risk for the patient such as clinically significant cardiac arrhythmias, e.g., sustained ventricular tachycardia, second or third degree heart block without a pacemaker
5. History or additional risk factors for Torsade de Pointes such as heart failure, hypokalemia, familial long QT syndrome or known family history of Torsade de Pointes
6. Repeated demonstration of resting QTcF > 480 msec at screening
7. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases
8. Pregnant or nursing (lactating) females.
9. Females of child-bearing potential, unless they are using effective methods of contraception while taking study treatment and throughout their MDR-TB treatment.
10. Sexually active males who are not willing to use a condom during intercourse while taking study treatment and throughout their MDR-TB treatment. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid.
11. Infected with a strain of MTB susceptible to rifampin.
12. Identified at screening or from previous drug susceptibility results to be infected with a strain of MTB that demonstrates a pre-XDR- or XDR-TB pattern of resistance.
13. Complicated or severe extrapulmonary manifestations of TB.
14. Critically ill, and in the judgment of the investigator, unlikely to survive more than 6 months
15. Unable to take oral medication
16. Unable to attend or comply with treatment or follow-up schedule.
17. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 times the upper limit of normal (ULN).
18. Any condition (social or medical) which in the opinion of the investigator would make study participation unsafe.
19. Taking any medications contraindicated with the medicines in either the experimental or active control regimen as listed in the protocol



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

Treatment of multidrug-resistant pulmonary tuberculosis
MedDRA version: 18.1 Level: LLT Classification code 10070578 Term: Multidrug resistant tuberculosis System Organ Class: 100000004862

Intervention(s)

Trade Name: LAMPRENE 50 mg
Product Code: LAM320B
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: Clofazimine
CAS Number: 2030-63-9
Current Sponsor code: LAM320B
Other descriptive name: CLOFAZIMINE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Trade Name: LAMPRENE 100 mg
Product Code: LAM320B
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: Clofazimine
CAS Number: 2030-63-9
Current Sponsor code: LAM320B
Other descriptive name: CLOFAZIMINE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Throughout the 30 month treatment period

Primary end point(s): Please refer to the section E.2.1 (Main objective of the trial)

Main Objective: The primary objective is to evaluate the effect of clofazimine added to BR over BR alone in producing higher cure rates at Month 30 post-randomization based on liquid culture media results in Mycobacterial Growth Indicator Tube (MGIT).

Secondary Objective: Evaluate the difference between clofazimine added to BR and BR alone with regard to:
1. Time to sputum culture conversion at Week 24 using liquid culture media (surrogate endpoint).
2. Proportion of patients achieving sputum culture conversion at Week 24 using liquid culture media.
3. Time to positive signal of MTB growth in liquid culture media, using a repeated measures mixed effects model analysis.
4. Safety and tolerability.
5. Routine safety electrocardiogram (ECG) parameters, including QRS complex (QRS), PR interval (PR), QT interval (QT), QT interval corrected by Fredericia method (QTcF) and heart rate.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Secondary objective [Timepoint(s)]:
1. Time to sputum culture conversion at Week 24 using liquid culture media (surrogate endpoint)[Week 24].
2. Proportion of patients achieving sputum culture conversion at Week 24 using liquid culture media[Week 24].
3. Time to positive signal of MTB growth in liquid culture media, using a repeated measures mixed effects model analysis[Week 24].
4. Safety and tolerability[Throughout the study].
5. Routine safety electrocardiogram (ECG) parameters, including QRS complex (QRS), PR interval (PR), QT interval (QT), QT interval corrected by Fredericia method (QTcF) and heart rate[Screening, Week 4, 8, 12, 18, 24, 36, 48, 64, 72, 84, 96 and 120].

Secondary end point(s): Please refer to the section E.2.2 (Secondary objectives of the trial)

Secondary ID(s)

2015-004440-19-LV

CLAM320B2202

Source(s) of Monetary Support

Novartis Pharma Services AG