Clinical trial NCT03069534: Study of Adjunctive Recombinant Human Interleukin-2 Therapy in Patients With MDR-TB
Official title: Study of Adjunctive rhIL-2 Therapy in Patients With MDR-TB That Improves Efficiency and Shortens Course
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: MDR TB
Keywords: MDR-TB
rhIL-2
immunotherapy
Lead sponsor: The First Affiliated Hospital with Nanjing Medical University
Sponsor class: OTHER
First posted: 2017-03-03
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Cure rate
timeFrame: 130 months
Secondary outcomes:
measure: sputum smear/culture conversion rate
timeFrame: 24 months
Other outcomes:
Locations:
city: Nanjing
country: China
facility: the First Affiliated Hospital of Nanjing Medical University
state: Jiangsu
Study officials:
affiliation: the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
name: Hong Wang, PH.D
role: PRINCIPAL_INVESTIGATOR
References: