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

Phase 2

• Conditions: MDR TB
• Interventions: Drug: RhIL-2

• Registration Number: NCT03069534
• Lead Sponsor: The First Affiliated Hospital with Nanjing Medical University

Brief 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.

Study Timeline

• Study Start: 2009-06-01
• Status Verified: 2009-09
• Study First Submitted: 2017-02-19
• Study First Submitted QC: 2017-02-27
• Last Update Submitted: 2017-02-27
• Study First Posted: 2017-03-03
• Last Update Posted: 2017-03-03
• Primary Completion: 2019-06-01
• Study Completion: 2020-03-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 500

Inclusion Criteria

Patients had/were:

1. a confirmed case of MDR-TB;
2. aged 18-70 years old;
3. a chest CT showing visible lung lesions, with or without holes;
4. a fasting plasma glucose of less than 7.8 mol/L and a normal fundus examination, if they were diabetic;
5. voluntarily joined this study and signed an informed consent form.

Exclusion Criteria

1. two or more total allergies or any drug or food allergies;
2. resistant to some drugs of this program;
3. severe disorders of liver, kidney, or hematologic system functions;
4. any metabolic diseases, autoimmune diseases, endocrine diseases, cancer, or HIV/AIDS;
5. a long-term use of immunosuppressive agents;
6. a blood system dysfunction;
7. a history of mental illness or epilepsy;
8. pregnant or lactating;
9. participated in another clinical trial in the last 3 months or were currently participating in other ongoing clinical trials;
10. long-term alcohol abuse>10 years and more than two alcoholic drinks per day);
11. any other factor rendering them unsuitable to participate in this project, such as a history of unreliability.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
rhIL-2 Group	RhIL-2	The patients in rhIL-2 Group were given consisted of four courses of low-dose rhIL-2 plus standard anti-tuberculosis chemotherapy. rhIL-2 (500，000U/m)regiman 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. Standard anti-MDR-TB chemotherapy regiman was totally 24 months,including 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.Then all the group patients were followed up for a minimum of 36 months.

Primary Outcome Measures

Name	Time	Method
Cure rate	130 months	Completion of treatment and at least five consecutive negative sputum cultures from samples collected at least 30 days apart or one positive sputum culture followed by a minimum of three consecutive negative cultures taken at least 30 days apart during the final 12 months of treatment;

Secondary Outcome Measures

Name	Time	Method
sputum smear/culture conversion rate	24 months	The proportions of MDR-TB patients in the two groups achieving sputum smear/culture conversion at the end of 24 months of treatment

Trial Locations

Locations (1)

the First Affiliated Hospital of Nanjing Medical University; 🇨🇳 Nanjing, Jiangsu, China