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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01638520
Recruitment Status : Active, not recruiting
First Posted : July 11, 2012
Last Update Posted : April 4, 2017
National University, Singapore
Information provided by (Responsible Party):
National University Hospital, Singapore

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Tuberculosis, Pulmonary Drug: Pascolizumab Drug: Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Safety and Efficacy of Blocking IL-4 With Pascolizumab in Patients Receiving Standard Combination Therapy for Pulmonary Tuberculosis (TB): a Randomized, Double-blind, Placebo-controlled, Proof-of-concept Clinical Trial
Study Start Date : June 2012
Actual Primary Completion Date : February 2017
Estimated Study Completion Date : July 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Tuberculosis

Arm Intervention/treatment
Experimental: Pascolizumab
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.
Drug: Pascolizumab
0.05mg/kg - 10mg/kg Pascolizumab according to dosing cohort

Placebo Comparator: Placebo
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.
Drug: Placebo
Saline (volume determined based on weight of patient, and cohort of enrollment)

Primary Outcome Measures :
  1. Efficacy - Time to detection on liquid culture of sputum on Week 8 [ Time Frame: 8 weeks post intervention ]
  2. Co-primary outcome measure - safety [ Time Frame: Upto 24 weeks via follow-up visits/assessments and 24-96 weeks via phone assessments ]
    Adverse events considered at least possibly related to study medication and that are classified by the site investigator as serious and/or grade IV severity

Secondary Outcome Measures :
  1. Sputum culture status (positive or negative) on liquid culture at week 8 [ Time Frame: 8 weeks ]
  2. Rate of change (area under the curve) from baseline to week 8 in the time to positivity in liquid culture of sputum [ Time Frame: 8 weeks ]
  3. Rate of change in serial sputum colony counts on solid cultures from baseline to week 8 [ Time Frame: 8 weeks ]
  4. Rate of change of RPF-dependent serial sputum colony counts from baseline to week 8 [ Time Frame: 8 weeks ]
  5. Sputum culture status (positive or negative) on solid culture at week 8 [ Time Frame: 8 weeks ]
  6. Rate of change of sputum smear lipid-body positive mycobacteria from baseline to week 8 [ Time Frame: 8 weeks ]
  7. Serum IL-4 levels (free and drug-bound) [ Time Frame: 24 weeks ]
  8. Time to resolution of fever [ Time Frame: 24 weeks ]
  9. Time to resolution of all TB symptoms [ Time Frame: 24 weeks ]
  10. Resolution of chest X-ray changes at week 24 [ Time Frame: 24 weeks ]
  11. Resolution of PET/MRI changes at week 8 and week 24 [ Time Frame: 24 weeks ]
  12. TB relapse at any time up to week 96 [ Time Frame: 96 weeks ]
  13. Anti-pascolizumab antibodies [ Time Frame: 24 weeks ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   21 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 )

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01638520

Institute of Respiratory Medicine
Kuala Lumpur, Malaysia
University Malaya Medical Centre
Kuala Lumpur, Malaysia
Lung Centre Philippines
Manila, Philippines
Philippines Tuberculosis Society Inc.
Manila, Philippines
Changi General Hospital
Singapore, Singapore
National University Hospital, Singapore
Singapore, Singapore
Ng Teng Fong General Hospital
Singapore, Singapore
Sponsors and Collaborators
National University Hospital, Singapore
National University, Singapore
Principal Investigator: Nick Paton National Univesity, Singapore

Responsible Party: National University Hospital, Singapore Identifier: NCT01638520     History of Changes
Other Study ID Numbers: DSRB 2012/02212
First Posted: July 11, 2012    Key Record Dates
Last Update Posted: April 4, 2017
Last Verified: March 2017

Keywords provided by National University Hospital, Singapore:
Immune Therapy
Interleukin 4
monoclonal antibody

Additional relevant MeSH terms:
Tuberculosis, Pulmonary
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections