Safety and Efficacy of Blocking IL-4 With Pascolizumab in Patients Receiving Standard Therapy for Pulmonary Tuberculosis

National University Health System (NUHS)

Status and phase: Unknown; Phase 2

Conditions: Tuberculosis, Pulmonary

Treatments: Drug: Placebo; Drug: Pascolizumab

Study type: Interventional

Funder types: Other

Identifiers

NCT01638520

DSRB 2012/02212

Details and patient eligibility

About

New approaches are needed to achieve more rapid elimination of dormant mycobacteria and thereby shorten treatment for drug-sensitive and drug-resistant tuberculosis (TB). Dormant mycobacteria are relatively resistant to antibacterial drugs and approaches that enhance immune clearance have the potential to be more effective. Interleukin-4 (IL-4) is a key cytokine in the immune response to TB that may impair the clearance of mycobacteria. We hypothesize that pascolizumab, an anti-IL-4 monoclonal antibody, might be of value as an adjunct to standard treatment.

The aims of this trial are to determine whether administration of pascolizumab as an adjunct to standard combination treatment for drug-sensitive TB produces changes in one or more parameters of bacterial or host response (including bacterial clearance, host clinical status, immune response, bacterial and host transcriptomics, lung imaging) that may indicate potential for enhanced sterilization and to confirm the safety of blocking IL-4 (previously demonstrated in healthy volunteers and patients with asthma) in patients with TB.

Enrollment: 32 patients

Sex: All

Ages: 21 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Aged 21 -75 years of age
2. Male or female: females eligible only if not of childbearing potential or agree to remain abstinent or use an appropriate contraceptive method during the study.
3. Confirmed pulmonary TB by smear microscopy and Gene Xpert™
4. Absence of rifampicin resistance on molecular probe (Gene Xpert™)
5. Estimated to be able to produce at least 5ml of sputum per 24 hour period.
6. No previous history of anti-TB therapy for active disease (treatment for latent disease acceptable).
7. Willing to comply with the study visits and procedures
8. Willing and able to provide written informed consent

Exclusion criteria

1. More than 28 days of standard anti-TB chemotherapy at the time of randomization.
2. Disseminated TB (lymphadenopathy is acceptable)
3. Underlying serious chronic diseases such as those of the liver, kidney disease, blood disorders and Type I diabetes (controlled Type II diabetes is acceptable) or any significant organ dysfunction.
4. History of myocardial infarction, congestive heart failure or arrhythmia within 6 months of screening
5. History or evidence of chronic alcohol consumption or drug abuse
6. Current autoimmune disease or history of autoimmune disease.
7. Known or suspected hypersensitivity to any component of the trial medication (sodium phosphate, sodium chloride, glycine, sucrose, polysorbate 80)
8. Chronic use of an immunosuppressant
9. Treatment with any monoclonal antibody within 6 months of randomization
10. Vaccination within the 6 weeks prior to randomization (patients who have received influenza vaccination can enroll at 2 weeks following vaccination).
11. Seropositive for human immunodeficiency virus-1 or 2; hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies at screening
12. Creatinine > 1.4 times upper limit of normal or ALT greater than 2.5 times upper limit of normal on screening blood tests
13. QTc >450 msec on ECG performed at screening
14. Women who are currently pregnant or breastfeeding
15. Any other significant condition that would, in the opinion of the investigator, compromise the patient's safety or outcome in the trial.
16. Participation in other clinical intervention trial or research protocol (Participation in other studies that do not involve an intervention may be allowed, but this must be discussed and approved by Chief Investigator )

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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32 participants in 2 patient groups, including a placebo group

Pascolizumab

Experimental group

Description:

The dose of study medication will be calculated using the patient's body weight and the appropriate dosing regimen based on the cohort of enrollment. The medication will be administered by slow intravenous infusion over 1 hour under close medical supervision.

Treatment:

Drug: Pascolizumab

Placebo

Placebo Comparator group

Description:

For patients randomized to placebo, Sterile 0.9% w/v Sodium Chloride will be used for Injection, using the same volume that would have been prepared if the patient had been randomized to receive pascolizumab.

Treatment:

Drug: Placebo