Tuberculosis, PulmonaryPhase 2NCT01638520
Safety and Efficacy of Blocking IL-4 With Pascolizumab in Patients Receiving Standard Therapy for Pulmonary Tuberculosis
A Phase 2 study testing Pascolizumab in people with Tuberculosis, Pulmonary, run by National University Hospital, Singapore at 7 sites in 3 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 21 to 75 years
- Conditions the study is for
- Tuberculosis, Pulmonary
- What is being tested?
- Pascolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 7 sitesin 3 countries
- Study dates
- Jun 2012to Jul 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged 21 -75 years of age
- 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.
- Confirmed pulmonary TB by smear microscopy and Gene Xpert™
- Absence of rifampicin resistance on molecular probe (Gene Xpert™)
- Estimated to be able to produce at least 5ml of sputum per 24 hour period.
- No previous history of anti-TB therapy for active disease (treatment for latent disease acceptable).
- Willing to comply with the study visits and procedures
- Willing and able to provide written informed consent
Who cannot join
- More than 28 days of standard anti-TB chemotherapy at the time of randomization.
- Disseminated TB (lymphadenopathy is acceptable)
- 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.
- History of myocardial infarction, congestive heart failure or arrhythmia within 6 months of screening
- History or evidence of chronic alcohol consumption or drug abuse
- Current autoimmune disease or history of autoimmune disease.
Show all 16Show fewer
- Known or suspected hypersensitivity to any component of the trial medication (sodium phosphate, sodium chloride, glycine, sucrose, polysorbate 80)
- Chronic use of an immunosuppressant
- Treatment with any monoclonal antibody within 6 months of randomization
- Vaccination within the 6 weeks prior to randomization (patients who have received influenza vaccination can enroll at 2 weeks following vaccination).
- Seropositive for human immunodeficiency virus-1 or 2; hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies at screening
- Creatinine > 1.4 times upper limit of normal or ALT greater than 2.5 times upper limit of normal on screening blood tests
- QTc >450 msec on ECG performed at screening
- Women who are currently pregnant or breastfeeding
- Any other significant condition that would, in the opinion of the investigator, compromise the patient's safety or outcome in the trial.
- 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 locations and contacts
7 sites in 3 countries.
7 sites in 3 countries
Singapore3 sites
Changi General Hospital
Singapore
National University Hospital, Singapore
Singapore
Ng Teng Fong General Hospital
Singapore
Malaysia2 sites
Institute of Respiratory Medicine
Kuala Lumpur
University Malaya Medical Centre
Kuala Lumpur
Philippines2 sites
Lung Centre Philippines
Manila
Philippines Tuberculosis Society Inc.
Manila
About this study
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
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.
- Conditions
- Tuberculosis, Pulmonary
- Being tested
- Pascolizumab, Placebo
- Keywords
- Immune Therapy, Interleukin 4, monoclonal antibody
- Medical subject headings
- Tuberculosis, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PascolizumabDrug
0.05mg/kg - 10mg/kg Pascolizumab according to dosing cohort
PlaceboDrug
Saline (volume determined based on weight of patient, and cohort of enrollment)
| Study group | Role | What they receive |
|---|---|---|
| Pascolizumab | Experimental | 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. Receives: Drug: Pascolizumab |
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy - Time to detection on liquid culture of sputum on Week 8
Measured: 8 weeks post intervention
Co-primary outcome measure - safety
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
Measured: Upto 24 weeks via follow-up visits/assessments and 24-96 weeks via phone assessments
Secondary outcomes (13)
Sputum culture status (positive or negative) on liquid culture at week 8
Measured: 8 weeks
Rate of change (area under the curve) from baseline to week 8 in the time to positivity in liquid culture of sputum
Measured: 8 weeks
Rate of change in serial sputum colony counts on solid cultures from baseline to week 8
Measured: 8 weeks
Rate of change of RPF-dependent serial sputum colony counts from baseline to week 8
Measured: 8 weeks
Sputum culture status (positive or negative) on solid culture at week 8
Measured: 8 weeks
Rate of change of sputum smear lipid-body positive mycobacteria from baseline to week 8
Measured: 8 weeks
Serum IL-4 levels (free and drug-bound)
Measured: 24 weeks
Time to resolution of fever
Measured: 24 weeks
Time to resolution of all TB symptoms
Measured: 24 weeks
Resolution of chest X-ray changes at week 24
Measured: 24 weeks
Resolution of PET/MRI changes at week 8 and week 24
Measured: 24 weeks
TB relapse at any time up to week 96
Measured: 96 weeks
Anti-pascolizumab antibodies
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2012 (estimated)
- Study startJun 2012
- Primary completionFeb 2017
- Study completionJul 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Tuberculosis, PulmonaryStudies of the same condition, open and under way.
- More trials run by National University Hospital, SingaporeThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Collaborators
- National University of Singapore
- Responsible party
- Sponsor
- Investigators
- Nick Paton, Principal investigator, National Univesity, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01638520
- Sponsor's protocol ID
- DSRB 2012/02212
- Status last verified
- Mar 2017
- First submitted
- 9 Jul 2012
- Last updated
- 4 Apr 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Paton NI, Gurumurthy M, Lu Q, Leek F, Kwan P, Koh HWL, Molton J, Mortera L, Naval S, Bakar ZA, Pang YK, Lum L, Lim TK, Cross GB, Lekurwale G, Choi H, Au V, Connolly J, Hibberd M, Green JA; Pascolizumab Tuberculosis Trial Team. Adjunctive Pascolizumab in Rifampicin-Susceptible Pulmonary Tuberculosis: Proof-of-Concept, Partially-Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Trial. J Infect Dis. 2024 Sep 23;230(3):590-597. doi: 10.1093/infdis/jiae104.
PubMed 38527849
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01638520
- Acronym / sponsor ID
- DSRB 2012/02212
- Conditions
- Tuberculosis, Pulmonary
- Keywords
- Immune Therapy, Interleukin 4, monoclonal antibody
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 32 participants (actual)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Collaborators
- National University of Singapore
- Study start
- Jun 2012
- Primary completion
- Feb 2017 (actual)
- Study completion
- Jul 2017 (estimated)
- First posted
- 11 Jul 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pascolizumab | Experimental | Drug: PascolizumabThe 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. |
| Placebo | Placebo comparator | Drug: PlaceboFor 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. |
Who may qualify
- Ages
- 21 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Aged 21 -75 years of age
- 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.
- Confirmed pulmonary TB by smear microscopy and Gene Xpert™
- Absence of rifampicin resistance on molecular probe (Gene Xpert™)
- Estimated to be able to produce at least 5ml of sputum per 24 hour period.
Key exclusion criteria (16 listed)
- More than 28 days of standard anti-TB chemotherapy at the time of randomization.
- Disseminated TB (lymphadenopathy is acceptable)
- 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.
- History of myocardial infarction, congestive heart failure or arrhythmia within 6 months of screening
- History or evidence of chronic alcohol consumption or drug abuse
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pascolizumab0.05mg/kg - 10mg/kg Pascolizumab according to dosing cohort | Drug | Pascolizumab |
| PlaceboSaline (volume determined based on weight of patient, and cohort of enrollment) | Drug | Placebo |
Primary outcome
Efficacy - Time to detection on liquid culture of sputum on Week 8
Time frame: 8 weeks post intervention
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
13 secondary outcomes
Sputum culture status (positive or negative) on liquid culture at week 8
Time frame: 8 weeks
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
Rate of change in serial sputum colony counts on solid cultures from baseline to week 8
Time frame: 8 weeks
Rate of change of RPF-dependent serial sputum colony counts from baseline to week 8
Time frame: 8 weeks
Sputum culture status (positive or negative) on solid culture at week 8
Time frame: 8 weeks
Rate of change of sputum smear lipid-body positive mycobacteria from baseline to week 8
Time frame: 8 weeks
Serum IL-4 levels (free and drug-bound)
Time frame: 24 weeks
Time to resolution of fever
Time frame: 24 weeks
Time to resolution of all TB symptoms
Time frame: 24 weeks
Resolution of chest X-ray changes at week 24
Time frame: 24 weeks
Resolution of PET/MRI changes at week 8 and week 24
Time frame: 24 weeks
TB relapse at any time up to week 96
Time frame: 96 weeks
Anti-pascolizumab antibodies
Time frame: 24 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2017.
- Derived from this study: PubMed 38527849Paton NI, Gurumurthy M, Lu Q, Leek F, Kwan P, Koh HWL, Molton J, Mortera L, Naval S, Bakar ZA, Pang YK, Lum L, Lim TK, Cross GB, Lekurwale G, Choi H, Au V, Connolly J, Hibberd M, Green JA; Pascolizumab Tuberculosis Trial Team. Adjunctive Pascolizumab in Rifampicin-Susceptible Pulmonary Tuberculosis: Proof-of-Concept, Partially-Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Trial. J Infect Dis. 2024 Sep 23;230(3):590-597. doi: 10.1093/infdis/jiae104.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nick Paton principal investigator
National Univesity, Singapore
7 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pascolizumab in people with Tuberculosis, Pulmonary, run by National University Hospital, Singapore at 7 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 4 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Singapore, Malaysia, Philippines. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy - Time to detection on liquid culture of sputum on Week 8 (time frame: 8 weeks post intervention). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01638520, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2017.