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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01400503
First received: April 21, 2011
Last updated: August 26, 2014
Last verified: August 2014

April 21, 2011
August 26, 2014
April 2011
March 2015   (final data collection date for primary outcome measure)
Number of Patients with Adverse Events [ Time Frame: Up to 6 years ] [ Designated as safety issue: Yes ]
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.
The occurrence of adverse events [ Time Frame: Up to 4 years ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01400503 on ClinicalTrials.gov Archive Site
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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).
  • The Multicentric Castleman's Disease Symptom Scale (MCDSS) as a measure of the severity of symptoms [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
  • Pharmacodynamic assessments of interleukin-6 (IL-6) [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
  • Glycoform clearance [ Time Frame: Up to 6 weeks ] [ Designated as safety issue: No ]
  • In vivo protein degradation analysis [ Time Frame: Up to 6 weeks ] [ Designated as safety issue: No ]
  • Proportion of previously responding patients and siltuximab-naive patients who maintain disease control [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
  • Duration of disease control and survival [ Time Frame: Up to and after the 4-year data cutoff ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Study to Evaluate the Safety of Long-term Treatment With Siltuximab in Patients With Multicentric Castleman's Disease
An Open-label, Multicenter Study to Evaluate the Safety of Long-term Treatment With Siltuximab in Subjects With Multicentric Castleman's Disease

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

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.

Interventional
Phase 2
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Multicentric Castleman's Disease
Drug: Siltuximab
Type=exact number, unit=mg/kg, number=11, form=intravenous solution, route=intravenous. Siltuximab given as a 1-hour infusion every 3 weeks.
Experimental: Siltuximab
Siltuximab 11 mg/kg, intravenous infusion, given as a 1-hour infusion every 3 weeks.
Intervention: Drug: Siltuximab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
60
March 2017
March 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Has multicentric Castleman's disease
  • Have previously been enrolled in Study C0328T03 or CNTO328MCD2001 (either treatment arm)
  • Have had their last administration of study treatment (siltuximab or placebo) less than 6 weeks (window of plus 2 weeks) prior to first dose
  • Patients must not have had disease progression while receiving siltuximab. For those patients originally assigned to placebo in the CNTO328MCD2001 study, patients who have received less than 4 months of siltuximab following crossover will also be eligible
  • Have adequate clinical laboratory parameters within 2 weeks prior to the first dose of siltuximab for this study

Exclusion Criteria:

  • Unmanageable toxicity, an adverse event, progression of disease, or withdrawal of consent as reason for discontinuing treatment from previous sponsor-initiated siltuximab study
  • Vaccination with live, attenuated vaccines within 4 weeks of first dose of this study
  • Known unmanageable allergies, hypersensitivity, intolerance to monoclonal antibodies, to murine, chimeric, human proteins or their excipients
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Belgium,   Brazil,   Canada,   China,   Egypt,   France,   Germany,   Hong Kong,   Israel,   Korea, Republic of,   New Zealand,   Norway,   Singapore,   Spain,   Taiwan,   United Kingdom
 
NCT01400503
CR018469, CNTO328MCD2002, 2010-022837-27
No
Janssen Research & Development, LLC
Janssen Research & Development, LLC
Not Provided
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
Janssen Research & Development, LLC
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP