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

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

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.

Study Overview

• Status: Unknown
• Conditions: MDR TB
• Intervention / Treatment: Drug: RhIL-2

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 Type: Interventional
• Enrollment (Anticipated): 500
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Qi Tan, PH.D; Phone Number: +8613584097282; Email: aqua18345760@hotmail.com

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Recruiting
      • The First Affiliated Hospital of Nanjing Medical University
      • Contact: Qi Tan, PH.D; Phone Number: +8613584097282; Email: aqua18345760@hotmail.com
      • Sub-Investigator: Qi Tan, PH.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: rhIL-2 Group; 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.	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.
NO_INTERVENTION: Control Group; The patients in Control Group were given standard anti-tuberculosis chemotherapy regiman.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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cure rate	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;	130 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University
• Investigators: Principal Investigator: Hong Wang, PH.D, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2009
• Primary Completion (ANTICIPATED): June 1, 2019
• Study Completion (ANTICIPATED): March 1, 2020

Study Registration Dates

• First Submitted: February 19, 2017
• First Submitted That Met QC Criteria: February 27, 2017
• First Posted (ACTUAL): March 3, 2017

Study Record Updates

• Last Update Posted (ACTUAL): March 3, 2017
• Last Update Submitted That Met QC Criteria: February 27, 2017
• Last Verified: September 1, 2009

More Information

Terms related to this study

• Keywords: immunotherapy; MDR-TB; rhIL-2
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Tuberculosis, Multidrug-Resistant
• Other Study ID Numbers: rhIL-2 Therapy ON MDR-TB

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No