NCT03069534

Study of Adjunctive Recombinant Human Interleukin-2 Therapy in Patients With MDR-TB

Study of Adjunctive rhIL-2 Therapy in Patients With MDR-TB That Improves Efficiency and Shortens Course

• Status: Unknown
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 500 (estimated)
• Sponsor: The First Affiliated Hospital with Nanjing Medical University · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

Multidrug-resistant tuberculosis (MDR-TB) has emerged as a challenge worldwide. Few studies have prospectively reported outcomes in patients with pulmonary MDR-TB treated with adjunctive immunotherapy combined to standard chemotherapy. We aimed to assess whether immunotherapy with Interleukin(IL)-2 enhanced the clinical and immune effects of treatment on MDR-TB patients.We performed a multicentre prospective cohort study extend all over Jiangsu province in China. Two groups were generated based on the adjunctive rhIL-2 therapy during 24 months regiman. Bacteriological and imaging data were followed during 24 months with cure rates analysed.

Detailed description

IL-2 therapy regimans are expected to restore the immune response or to change the immunologic status,thus allowing the host to more efficiently contain and eradicate immune responses, primarily those against cancers and infectious diseases.To address this, we performed a prospective randomized controlled multicenter cohort study of 8-month adjunctive immunotherapy with rhIL-2 for MDR-TB patients compared with the standard chemotherapy. This multicenter prospective clinical study was conducted at 13 tuberculosis centers (coordinating hospital specialized in tuberculosis) across Jiangsu province, China. Joined by the network system of The First Affiliated Hospital of Nanjing Medical University and CDC of Jiangsu province, participants were enrolled from 2009 to 2018. This study protocol was approved by the ethics committee of the First Affiliated Hospital of Nanjing Medical University and was performed adhering to the ethical principles of the Declaration of Helsinki. All patients provided written informed consent before enrollment. The independent data and safety of the study were monitored by the hospital monitoring committee. Patients enrollment Eligible MDR-TB participants were identified by triplicate-spot sputum smears that were positive for acid-fast bacilli and a positive sputum culture with resistance to both isoniazid and rifampin, as determined by susceptibility tests and rapid screening tests . The results of these assays were confirmed using an L-G medium base modified in the Jiangsu province Centers for Disease Control and Prevention（CDC）. Treatment plan for the two cohorts: The patients in rhIL-2 group were given consisted of four courses of low-dose rhIL-2 (500，000 U/m) given subcutaneously (SC) once every other day (q.o.d.) for 30 days. Four courses were carried out separately during months 1, 3, 5, and 7. All enrolled patients with pulmonary MDR-TB received a 24-month standard anti-MDR-TB chemotherapy regimen:6-month Z+KM/AM or CM + PAS/(Pa) + PTO +LFX as an intensive phase treatment, followed by an 18-month Z + LFX + PTO + PAS/(Pa) as a consolidation phase treatment. (Z: Pyrazinamide; KM: Kanamycin; AM: Amikacin; CM: Capreomycin; LFX: Levofloxacin; PTO: Prothionamide; PAS: Para-aminosalicylicacid; Pa:Pasiniazid); After finishing treatment regimen patients were followed up for a minimum of 36- months or until discontinuation of regimen, withdrawal of consent, loss to follow-up, death, or end of study. For all of the participants demographic measurements were recorded on the first clinical visit. Patient data were collected at enrollment and quarterly intervals. Sputum smear conversion, sputum culture conversion and chest CT scan improvement were followed up at 3, 6, 12, 18, and 24 months for bacteriological and imaging data collected. Cure rates analysed and compared in both groups. The proportions of MDR-TB patients in the two groups achieving sputum smear/culture conversion, lung lesions absorption were assessed and compared. Safety assessment included clinical symptom observation, Incidences of adverse event （AE ）in two groups were assessed and compared. blood routine test, hematologic profile, blood biochemical examination including hepatic aminotransferase and blood ureantrogen/creatinine, blood electrolyte test (potassium, magnesium, calcium), serum thyroid stimulating hormone(TSH), audiology examinations, visual field and color examination. Cure rate was defined as first outcome. Sputum conversion rate was defined as second outcome.

Conditions

• MDR TB

Interventions

Type	Name	Description
DRUG	RhIL-2	RhIL-2 treatment intervention was consisted of four courses of low-dose rhIL-2 plus standard anti-tuberculosis chemotharapy. rhIL-2 (500,000 U/m)regimen was given subcutaneously (SC) once every other day (q.o.d.) for 30 days and four courses were carried out separately during months 1, 3, 5, and 7.

Timeline

• Start date: 2009-06-01
• Primary completion: 2019-06-01
• Completion: 2020-03-01
• First posted: 2017-03-03
• Last updated: 2017-03-03

Locations

1 site across 1 country: China

Regulatory

• FDA-regulated drug study