Safety and Efficacy of Blocking IL-4 With Pascolizumab in Patients Receiving Standard Therapy for Pulmonary Tuberculosis
30 maart 2017 bijgewerkt door: National University Hospital, Singapore
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.
Studie Overzicht
Toestand
Onbekend
Conditie
Interventie / Behandeling
Studietype
Ingrijpend
Inschrijving (Werkelijk)
32
Fase
- Fase 2
Contacten en locaties
In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.
Studie Locaties
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Manila, Filippijnen
- Lung Centre Philippines
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Manila, Filippijnen
- Philippines Tuberculosis Society Inc.
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Kuala Lumpur, Maleisië
- University Malaya Medical Centre
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Kuala Lumpur, Maleisië
- Institute of Respiratory Medicine
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Singapore, Singapore
- Changi General Hospital
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Singapore, Singapore
- National University Hospital, Singapore
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Singapore, Singapore
- Ng Teng Fong General Hospital
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Deelname Criteria
Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
21 jaar tot 75 jaar (Volwassen, Oudere volwassene)
Accepteert gezonde vrijwilligers
Nee
Geslachten die in aanmerking komen voor studie
Allemaal
Beschrijving
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
- 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 )
Studie plan
Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Dubbele
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Experimenteel: 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.
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0.05mg/kg - 10mg/kg Pascolizumab according to dosing cohort
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Placebo-vergelijker: 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.
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Saline (volume determined based on weight of patient, and cohort of enrollment)
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Efficacy - Time to detection on liquid culture of sputum on Week 8
Tijdsspanne: 8 weeks post intervention
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8 weeks post intervention
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Co-primary outcome measure - safety
Tijdsspanne: Upto 24 weeks via follow-up visits/assessments and 24-96 weeks via phone assessments
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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
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Upto 24 weeks via follow-up visits/assessments and 24-96 weeks via phone assessments
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Secundaire uitkomstmaten
Uitkomstmaat |
Tijdsspanne |
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Sputum culture status (positive or negative) on liquid culture at week 8
Tijdsspanne: 8 weeks
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8 weeks
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Rate of change (area under the curve) from baseline to week 8 in the time to positivity in liquid culture of sputum
Tijdsspanne: 8 weeks
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8 weeks
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Rate of change in serial sputum colony counts on solid cultures from baseline to week 8
Tijdsspanne: 8 weeks
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8 weeks
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Rate of change of RPF-dependent serial sputum colony counts from baseline to week 8
Tijdsspanne: 8 weeks
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8 weeks
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Sputum culture status (positive or negative) on solid culture at week 8
Tijdsspanne: 8 weeks
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8 weeks
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Rate of change of sputum smear lipid-body positive mycobacteria from baseline to week 8
Tijdsspanne: 8 weeks
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8 weeks
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Serum IL-4 levels (free and drug-bound)
Tijdsspanne: 24 weeks
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24 weeks
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Time to resolution of fever
Tijdsspanne: 24 weeks
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24 weeks
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Time to resolution of all TB symptoms
Tijdsspanne: 24 weeks
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24 weeks
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Resolution of chest X-ray changes at week 24
Tijdsspanne: 24 weeks
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24 weeks
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Resolution of PET/MRI changes at week 8 and week 24
Tijdsspanne: 24 weeks
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24 weeks
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TB relapse at any time up to week 96
Tijdsspanne: 96 weeks
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96 weeks
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Anti-pascolizumab antibodies
Tijdsspanne: 24 weeks
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24 weeks
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Medewerkers en onderzoekers
Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.
Medewerkers
Onderzoekers
- Hoofdonderzoeker: Nick Paton, National Univesity, Singapore
Studie record data
Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.
Bestudeer belangrijke data
Studie start
1 juni 2012
Primaire voltooiing (Werkelijk)
1 februari 2017
Studie voltooiing (Verwacht)
1 juli 2017
Studieregistratiedata
Eerst ingediend
9 juli 2012
Eerst ingediend dat voldeed aan de QC-criteria
9 juli 2012
Eerst geplaatst (Schatting)
11 juli 2012
Updates van studierecords
Laatste update geplaatst (Werkelijk)
4 april 2017
Laatste update ingediend die voldeed aan QC-criteria
30 maart 2017
Laatst geverifieerd
1 maart 2017
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- DSRB 2012/02212
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