Clinical Trial: A Study to Evaluate the Safety of Long-term Treatment With Siltuximab in Patients With Multicentric Castleman's Disease

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: An Open-label, Multicenter Study to Evaluate the Safety of Long-term Treatment With Siltuximab in Subjects With Multicentric Castleman's Disease

Brief Summary: The purpose of this study is to evaluate the long-term safety of siltuximab in patients with multicentric Castleman's disease (MCD).

Detailed Summary: This is an open-label (all people know the identity of the intervention), multicenter (study conducted in multiple sites), non-randomized (patients are not assigned by chance to treatment groups), Phase 2b study. Up to 75 patients with MCD will be eligible for the study, the majority of whom will be on active therapy with siltuximab at the time of enrollment. Patients will be either siltuximab-naive or have not progressed on siltuximab in the opinion of the investigator. Duration of disease control and survival will be assessed. Data collection for patients who discontinue treatment will be limited to survival, occurrence of malignancies, and subsequent therapies for MCD, which will be assessed twice per year until the patient has been lost to follow up or has withdrawn consent for the study, whichever occurs first. An interim analysis will be conducted (no later than 2 years after the start of enrollment) to further evaluate the benefit and safety of long-term treatment with siltuximab in patients with MCD. A data will occur at 6 years after the start of enrollment and for those patients remaining on treatment after the data cutoff, data collection will be limited to pregnancies and serious adverse events (SAEs), including information on study agent administration and concomitant medications associated with an SAE. Safety evaluations for adverse events, clinical laboratory tests, vital signs, and physical examination will be performed throughout the study. The end of study is the date of the last assessment for the last patient.
Sponsor: Janssen Research & Development, LLC

Current Primary Outcome: Number of Patients with Adverse Events [ Time Frame: Up to 6 years ]

An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.


Original Primary Outcome: The occurrence of adverse events [ Time Frame: Up to 4 years ]

Current Secondary Outcome:

  • Number of multicentric Castleman's disease patients evaluated for assessment of atypical IL-6 splice variants or cleavage fragments [ Time Frame: Up to 6 years ]
    Pharmacodynamic biomarker evaluations include assessment of atypical IL-6 splice variants or cleavage fragments.
  • Number of multicentric Castleman's disease patients evaluated for assessment of C-reactive protein [ Time Frame: Up to 6 years ]
    Pharmacodynamic biomarker evaluations include assessment of C-reactive protein.
  • Number of previously responding multicentric Castleman's disease patients and siltuximab-naive patients who maintain disease control [ Time Frame: Up to 6 years ]
    Disease assessments (including cutaneous assessments), are provided as a guide for assessing multicentric Castleman's disease.
  • Duration of multicentric Castleman's disease control [ Time Frame: Up to 6 years ]
    Disease assessments (including cutaneous assessments), are provided as a guide for assessing multicentric Castleman's disease.
  • Duration of survival for patients with multicentric Castleman's disease [ Time Frame: From randomization up to death, lost to follow-up or withdrawal of consent, whichever come first; until 6 years ]
    Disease assessments (including cutaneous assessments), are provided as a guide for assessing multicentric Castleman's disease.
  • Multicentric Castleman's Disease Symptom Scale scores [ Time Frame: Up to 12 weeks ]
    Multicentric Castleman's Disease Symptom Scale scores questionnaire will only be completed by the sub-population from the C0328T03 study. These scores will be calculated as a measure of severity of symptoms.
  • Assessment of glycoform clearance analysis [ Time Frame: Up to 6 weeks ]
    For evaluating the clearance and degradation of glycoforms after administration of siltuximab, 6 serum samples will be collected from 5 former C0328T03 patients (a limited number of samples are needed for this analysis).
  • Assessment of in vivo protein degradation analysis [ Time Frame: Up to 6 weeks ]
    Siltuximab will be isolated from the serum samples using an anti-Id antibody. The purified protein will be analyzed by liquid chromatography/mass spectroscopy techniques (intact mass and peptide mapping).


Original Secondary Outcome:

  • The Multicentric Castleman's Disease Symptom Scale (MCDSS) as a measure of the severity of symptoms [ Time Frame: Up to 12 weeks ]
  • Pharmacodynamic assessments of interleukin-6 (IL-6) [ Time Frame: Up to 4 years ]
  • Glycoform clearance [ Time Frame: Up to 6 weeks ]
  • In vivo protein degradation analysis [ Time Frame: Up to 6 weeks ]
  • Proportion of previously responding patients and siltuximab-naive patients who maintain disease control [ Time Frame: Up to 4 years ]
  • Duration of disease control and survival [ Time Frame: Up to and after the 4-year data cutoff ]


Information By: Janssen Research & Development, LLC

Dates:
Date Received: April 21, 2011
Date Started: April 1, 2011
Date Completion: February 2, 2018
Last Updated: May 26, 2017
Last Verified: May 2017