Rifampin-resistant pulmonary tuberculosis MedDRA version: 20.0 Level: PT Classification code 10037440 Term: Pulmonary tuberculosis System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: CC-11050
Product Code: CC-11050
Pharmaceutical Form: Capsule
INN or Proposed INN: CC-11050
Current Sponsor code: CC-11050
Other descriptive name: N-[2-[(1S)-1-(3-ethoxy-4-methoxyphenyl)-
Sponsors
The Aurum Institute
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged 16 to 65 years 2. Able and willing to provide signed written consent or witnessed oral con-sent in the case of illiteracy, prior to undertaking any trial-related procedures. In the case of children 16 or 17 years of age, consent of at least one parent or guardian plus assent of the child will be required. 3. Body weight (in light clothing without shoes) between 30 and 90 kg. 4. Positive sputum Xpert (TB/RIF or Ultra) with Ct =22, with subsequent culture confirmation. 5. RIF resistance diagnosed by Xpert OR Hain test OR phenotypic drug susceptibility test 6. Chest radiograph meeting National TB Association criteria for moderate or far advanced pulmonary tuberculosis1 7. If sexually active, willing to use an effective contraceptive method for the duration of TB treatment 8. HIV-1 seronegative, OR if HIV-1 seropositive, presenting to an African study site with a CD4 T cell count >100/µl, and either currently receiving ART or willing to start ART during study participation as specified NB: HIV+ patients will only be enrolled at African sites Are the trial subjects under 18? yes Number of subjects for this age range: 330 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 310 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Any condition for which participation in the trial, as judged by the investigator, could compromise the well-being of the subject or prevent, limit or confound protocol specified assessments 2. Current or imminent (within 24 hr) treatment for malaria. 3. Pregnancy or breastfeeding 4. Is critically ill, such that in the judgment of the investigator, death is likely during the trial. 5. TB meningitis or other forms of severe TB with high risk of a poor outcome as judged by the investigator. 6. History of allergy or hypersensitivity to any of the trial therapies or related substances 7. Having participated in other clinical trials with investigational agents within 8 wks prior to trial start or currently enrolled in an investigational trial. 8. Prior RIF-R-TB treatment in the preceding 12 months 9. Cardiac arrhythmia requiring medication, or any clinically significant ECG abnormality, in the opinion of the investigator 10. Patients requiring treatment with drugs that are strong CYP3A4 inducers or inhibitors (eg, ketoconazole, lopinavir, or cobicistat), carbonic anhydrase inhibitors (eg, acetazolamide), or OCT2 or MATE inhibitors (eg, cimetidine, pyrimethamine). 11. Use of systemic corticosteroids within the past 28 days. 12. History of unstable diabetes mellitus that required hospitalization for hyper- or hypo-glycaemia within the past year prior to start of screening, or requiring treatment with metformin. 13. Subjects with any of the following abnormal laboratory values: a. creatinine >2 mg/dL b. haemoglobin 5.0 x ULN g. total bilirubin >1.5 mg/dL h. Hepatitis B surface antigen positive i. random blood glucose >140 mg/dL (7.8 mmol/L) j. SARS-CoV-2 PCR or antigen test positive NB: All of the inclusion and none of the exclusion criteria must be met NB: Enrolled patients whose baseline sputum cultures subsequently fail to show growth of RIF-R-TB will be excluded from the mITT and PP populations. They may be removed from further study participation based on their individual benefit-risk balance, as assessed by the site and study PIs and the DMC.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To examine the safety, tolerability, and preliminary efficacy of two adjunctive TB-HDTs (one anti-inflammatory, and one antimicrobial) in patients with rifampin-resistant pulmonary tuberculosis. Efficacy endpoints will include measures of recovery of lung function and eradication of M tuberculosis infection. ;Secondary Objective: Not applicable;Primary end point(s): There are two co-primary endpoints: 1. FEV1 at month 6 2. Likelihood of stable culture conversion through month 6 Both co-primary endpoints must be met for a treatment to be considered successful. The CC-11050 and metformin arms will each be compared to the control arm. ;Timepoint(s) of evaluation of this end point: month 6 (nominal 4-week months) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints: 1. FEV1 and FVC at additional time points (2, 6, and 18 months) 2. FEV1 and FVC slope over time 3. Proportions of patients with negative sputum cultures after 2 and 6 months of treatment 4. The proportion of patients with new TB drug resistance 5. Proportions of patients whose treatment is considered unsuccessful due to failure, relapse, or death, individually and in total 6. TE-SAEs, categorized according to severity, treatment relatedness, and leading to early withdrawal 7. Quantitative and qualitative clinical and laboratory safety measurements, including observed and change from baseline 8. Proportion of patients with disease exacerbation (paradoxical reactions or IRIS) Exploratory endpoints: 1. Lung radiodensity by chest CT, measured at baseline and month 4 2. PK/PD analysis based on sparse sampling ;Timepoint(s) of evaluation of this end point: Up to 18 months after study entry | — |
Countries
Georgia, Moldova, Republic of, Mozambique, Romania, South Africa
Contacts
Public ContactChief Science Officer
The Aurum Institute
Outcome results
None listed