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

30 de marzo de 2017 actualizado por: 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.

Descripción general del estudio

Estado

Desconocido

Condiciones

Intervención / Tratamiento

Tipo de estudio

Intervencionista

Inscripción (Actual)

32

Fase

  • Fase 2

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

  • Filipinas
      • Manila, Filipinas
        • Lung Centre Philippines
      • Manila, Filipinas
        • Philippines Tuberculosis Society Inc.
  • Malasia
      • Kuala Lumpur, Malasia
        • University Malaya Medical Centre
      • Kuala Lumpur, Malasia
        • Institute of Respiratory Medicine
  • Singapur
      • Singapore, Singapur
        • Changi General Hospital
      • Singapore, Singapur
        • National University Hospital, Singapore
      • Singapore, Singapur
        • Ng Teng Fong General Hospital

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

21 años a 75 años (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

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 )

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Doble

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
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.
Droga: Pascolizumab
0.05mg/kg - 10mg/kg Pascolizumab according to dosing cohort
Comparador de placebos: 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.
Droga: Placebo
Saline (volume determined based on weight of patient, and cohort of enrollment)

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Efficacy - Time to detection on liquid culture of sputum on Week 8
Periodo de tiempo: 8 weeks post intervention
8 weeks post intervention
Co-primary outcome measure - safety
Periodo de tiempo: 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
Upto 24 weeks via follow-up visits/assessments and 24-96 weeks via phone assessments

Medidas de resultado secundarias

Medida de resultado
Periodo de tiempo
Sputum culture status (positive or negative) on liquid culture at week 8
Periodo de tiempo: 8 weeks
8 weeks
Rate of change (area under the curve) from baseline to week 8 in the time to positivity in liquid culture of sputum
Periodo de tiempo: 8 weeks
8 weeks
Rate of change in serial sputum colony counts on solid cultures from baseline to week 8
Periodo de tiempo: 8 weeks
8 weeks
Rate of change of RPF-dependent serial sputum colony counts from baseline to week 8
Periodo de tiempo: 8 weeks
8 weeks
Sputum culture status (positive or negative) on solid culture at week 8
Periodo de tiempo: 8 weeks
8 weeks
Rate of change of sputum smear lipid-body positive mycobacteria from baseline to week 8
Periodo de tiempo: 8 weeks
8 weeks
Serum IL-4 levels (free and drug-bound)
Periodo de tiempo: 24 weeks
24 weeks
Time to resolution of fever
Periodo de tiempo: 24 weeks
24 weeks
Time to resolution of all TB symptoms
Periodo de tiempo: 24 weeks
24 weeks
Resolution of chest X-ray changes at week 24
Periodo de tiempo: 24 weeks
24 weeks
Resolution of PET/MRI changes at week 8 and week 24
Periodo de tiempo: 24 weeks
24 weeks
TB relapse at any time up to week 96
Periodo de tiempo: 96 weeks
96 weeks
Anti-pascolizumab antibodies
Periodo de tiempo: 24 weeks
24 weeks

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

National University Hospital, Singapore

Colaboradores

National University, Singapore

Investigadores

  • Investigador principal: Nick Paton, National Univesity, Singapore

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio

1 de junio de 2012

Finalización primaria (Actual)

1 de febrero de 2017

Finalización del estudio (Anticipado)

1 de julio de 2017

Fechas de registro del estudio

Enviado por primera vez

9 de julio de 2012

Primero enviado que cumplió con los criterios de control de calidad

9 de julio de 2012

Publicado por primera vez (Estimar)

11 de julio de 2012

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

4 de abril de 2017

Última actualización enviada que cumplió con los criterios de control de calidad

30 de marzo de 2017

Última verificación

1 de marzo de 2017

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • DSRB 2012/02212

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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