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A Study Comparing Siltuximab Plus Best Supportive Care to Placebo Plus Best Supportive Care in Anemic Patients With International Prognostic Scoring System Low- or Intermediate-1-Risk Myelodysplastic Syndrome

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ClinicalTrials.gov Identifier: NCT01513317
Recruitment Status : Terminated (The study was stopped after the interim analysis based on lack of sufficient efficacy. There were no safety concerns.)
First Posted : January 20, 2012
Results First Posted : September 29, 2014
Last Update Posted : September 29, 2014
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Myelodysplastic Syndrome
Interventions Drug: Siltuximab
Drug: Placebo
Drug: Best supportive care (BSC)
Enrollment 76
Recruitment Details 76 participants were enrolled at 6 sites in Spain, 5 sites in the United States, 4 sites in Belgium, 3 sites each in Australia and the Russian Federation, 2 sites in the Netherlands, and 1 site in Sweden.
Pre-assignment Details All 76 participants were enrolled and randomly assigned in the study.
Arm/Group Title Siltuximab Placebo
Hide Arm/Group Description 15 mg/kg of siltuximab administered as a 1-hour infusion every 4 weeks + best supportive care (BSC) Placebo administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)
Period Title: Overall Study
Started 50 26
Completed 16 2
Not Completed 34 24
Reason Not Completed
Withdrawal by Subject             15             4
Death             1             1
Study terminated by sponsor             18             18
Not specified             0             1
Arm/Group Title Siltuximab Placebo Total
Hide Arm/Group Description 15 mg/kg of siltuximab administered as a 1-hour infusion every 4 weeks + best supportive care (BSC) Placebo administered as a 1-hour infusion every 4 weeks + best supportive care (BSC) Total of all reporting groups
Overall Number of Baseline Participants 50 26 76
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 50 participants 26 participants 76 participants
70.2  (7.7) 72  (7.61) 70.8  (7.67)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants 26 participants 76 participants
Female
23
  46.0%
9
  34.6%
32
  42.1%
Male
27
  54.0%
17
  65.4%
44
  57.9%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 50 participants 26 participants 76 participants
Australia 3 2 5
Belgium 4 4 8
Netherlands 2 1 3
Russian Federation 5 3 8
Spain 10 5 15
Sweden 3 0 3
United States 23 11 34
1.Primary Outcome
Title Percentage of Participants Who Achieved a Reduction in Red Blood Cell (RBC) Transfusions to Treat Anemia of Myelodysplastic Syndrome (MDS)
Hide Description Reduction in RBC transfusions to treat the anemia of MDS is defined as a ≥50 percentage relative decrease and a ≥2 unit absolute decrease in RBC transfusions in the 8 weeks before the unblinding (scheduled to occur after 12 weeks of treatment) compared with RBC transfusions in the 8 weeks before the date the informed consent form was signed.
Time Frame Up to Week 13
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: Included all randomized participants
Arm/Group Title Siltuximab Placebo
Hide Arm/Group Description:
15 mg/kg of siltuximab administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)
Placebo administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)
Overall Number of Participants Analyzed 50 26
Measure Type: Number
Unit of Measure: Percentage of participants
12 3.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Siltuximab, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.271
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in proportions
Estimated Value 0.082
Confidence Interval (2-Sided) 95%
-0.03 to 0.20
Estimation Comments The estimated parameter is the difference in proportion of participants who had a reduction in RBC transfusion to treat the anemia of MDS.
2.Secondary Outcome
Title Change From Baseline in the Mean Hemoglobin Concentrations at Week 13
Hide Description [Not Specified]
Time Frame Baseline and Week 13
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: Included all randomized participants with evaluable data at Week 13
Arm/Group Title Siltuximab Placebo
Hide Arm/Group Description:
15 mg/kg of siltuximab administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)
Placebo administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)
Overall Number of Participants Analyzed 31 18
Mean (Standard Deviation)
Unit of Measure: g/dL
-0.07  (1.503) -0.13  (1.375)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Siltuximab, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.872
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value 0.07
Confidence Interval (2-Sided) 95%
-0.79 to 0.93
Estimation Comments The estimated parameter is the difference in LS means of the change from baseline hemoglobin levels at Week 13.
3.Secondary Outcome
Title Percentage of Participants Achieving Hemoglobin Improvement (≥1.5 g/dL Increase From Baseline) Unrelated to Red Blood Cell (RBC) Transfusion at Week 13
Hide Description [Not Specified]
Time Frame Week 13
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: Included all randomized participants
Arm/Group Title Siltuximab Placebo
Hide Arm/Group Description:
15 mg/kg of siltuximab administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)
Placebo administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)
Overall Number of Participants Analyzed 50 26
Measure Type: Number
Unit of Measure: Percentage of Participants
8.0 3.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Siltuximab, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.494
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in proportions
Estimated Value 0.042
Confidence Interval (2-Sided) 95%
-0.06 to 0.15
Estimation Comments The estimated parameter is the difference in proportion of participants achieving hemoglobin improvement at Week 13.
4.Secondary Outcome
Title Percentage of Participants Who Did Not Require a Red Blood Cell (RBC) Transfusions to Treat Anemia of Myelodysplastic Syndrome (MDS) in the 8 Weeks of Treatment Before Unblinding at Week 13
Hide Description [Not Specified]
Time Frame 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: Included all randomized participants
Arm/Group Title Siltuximab Placebo
Hide Arm/Group Description:
15 mg/kg of siltuximab administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)
Placebo administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)
Overall Number of Participants Analyzed 50 26
Measure Type: Number
Unit of Measure: Percentage of Participants
4.0 3.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Siltuximab, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.986
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in proportions
Estimated Value 0.002
Confidence Interval (2-Sided) 95%
-0.09 to 0.09
Estimation Comments The estimated parameter is the difference in proportion of participants who did not require a blood transfusion in the 8 weeks of treatment before unblinding at Week 13.
5.Secondary Outcome
Title Mean Changes From Baseline in Percentages of Bone Marrow Blast Cells at Week 13
Hide Description [Not Specified]
Time Frame Baseline and Week 13
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: Included all randomized participants with evaluable data at Week 13
Arm/Group Title Siltuximab Placebo
Hide Arm/Group Description:
15 mg/kg of siltuximab administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)
Placebo administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)
Overall Number of Participants Analyzed 31 15
Mean (Standard Deviation)
Unit of Measure: Percentage of Bone Marrow Blast Cells
2.1  (8.22) 0.2  (2.08)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Siltuximab, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.363
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value 1.96
Confidence Interval (2-Sided) 95%
-2.35 to 6.27
Estimation Comments The estimated parameter is the difference in LS means for changes from baseline in bone marrow blasts at Week 13.
6.Secondary Outcome
Title Median Number of Red Blood Cell (RBC) Transfusions to Treat Anemia of Myelodysplastic Syndrome (MDS) During the 8 Weeks of Treatment Before Unblinding at Week 13
Hide Description [Not Specified]
Time Frame 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: Included all randomized participants who completed Week 13 unblinding
Arm/Group Title Siltuximab Placebo
Hide Arm/Group Description:
15 mg/kg of siltuximab administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)
Placebo administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)
Overall Number of Participants Analyzed 36 22
Median (Full Range)
Unit of Measure: RBC Transfusions
6.0
(0 to 14)
6.5
(0 to 25)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Siltuximab, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.073
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -1.69
Confidence Interval (2-Sided) 95%
-3.55 to 0.17
Estimation Comments The estimated parameter is the difference in LS means of the number of RBC transfusions during the 8 weeks of treament before unblinding at Week 13.
Time Frame Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose.
Adverse Event Reporting Description Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
 
Arm/Group Title Siltuximab Placebo
Hide Arm/Group Description 15 mg/kg of siltuximab administered as a 1-hour infusion every 4 weeks + best supportive care (BSC) Placebo administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)
All-Cause Mortality
Siltuximab Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Siltuximab Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   10/50 (20.00%)   8/26 (30.77%) 
Blood and lymphatic system disorders     
Neutropenia * 1  0/50 (0.00%)  1/26 (3.85%) 
Cardiac disorders     
Acute Myocardial Infarction * 1  0/50 (0.00%)  1/26 (3.85%) 
Cardiac Failure Congestive * 1  0/50 (0.00%)  1/26 (3.85%) 
Cardiovascular Insufficiency * 1  0/50 (0.00%)  1/26 (3.85%) 
Ventricular Fibrillation * 1  0/50 (0.00%)  1/26 (3.85%) 
Gastrointestinal disorders     
Femoral Hernia * 1  1/50 (2.00%)  0/26 (0.00%) 
Intestinal Ischaemia * 1  1/50 (2.00%)  0/26 (0.00%) 
Nausea * 1  1/50 (2.00%)  0/26 (0.00%) 
Vomiting * 1  1/50 (2.00%)  0/26 (0.00%) 
General disorders     
Mucosal Haemorrhage * 1  0/50 (0.00%)  1/26 (3.85%) 
Hepatobiliary disorders     
Cirrhosis Alcoholic * 1  0/50 (0.00%)  1/26 (3.85%) 
Infections and infestations     
Cellulitis * 1  1/50 (2.00%)  0/26 (0.00%) 
Escherichia Bacteraemia * 1  1/50 (2.00%)  0/26 (0.00%) 
Pneumonia * 1  4/50 (8.00%)  0/26 (0.00%) 
Sepsis * 1  0/50 (0.00%)  1/26 (3.85%) 
Septic Shock * 1  1/50 (2.00%)  0/26 (0.00%) 
Soft Tissue Infection * 1  0/50 (0.00%)  1/26 (3.85%) 
Injury, poisoning and procedural complications     
Hip Fracture * 1  1/50 (2.00%)  1/26 (3.85%) 
Metabolism and nutrition disorders     
Dehydration * 1  1/50 (2.00%)  0/26 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Chronic Obstructive Pulmonary Disease * 1  1/50 (2.00%)  0/26 (0.00%) 
Vascular disorders     
Deep Vein Thrombosis * 1  1/50 (2.00%)  0/26 (0.00%) 
Peripheral Ischaemia * 1  0/50 (0.00%)  1/26 (3.85%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA Version 15.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Siltuximab Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   30/50 (60.00%)   18/26 (69.23%) 
Blood and lymphatic system disorders     
Neutropenia * 1  1/50 (2.00%)  2/26 (7.69%) 
Thrombocytopenia * 1  3/50 (6.00%)  1/26 (3.85%) 
Gastrointestinal disorders     
Abdominal Pain Upper * 1  3/50 (6.00%)  0/26 (0.00%) 
Constipation * 1  3/50 (6.00%)  1/26 (3.85%) 
Diarrhoea * 1  2/50 (4.00%)  4/26 (15.38%) 
Nausea * 1  4/50 (8.00%)  3/26 (11.54%) 
Vomiting * 1  0/50 (0.00%)  2/26 (7.69%) 
General disorders     
Asthenia * 1  2/50 (4.00%)  2/26 (7.69%) 
Oedema Peripheral * 1  8/50 (16.00%)  2/26 (7.69%) 
Hepatobiliary disorders     
Hepatic Function Abnormal * 1  5/50 (10.00%)  3/26 (11.54%) 
Infections and infestations     
Upper Respiratory Tract Infection * 1  2/50 (4.00%)  3/26 (11.54%) 
Metabolism and nutrition disorders     
Hypokalaemia * 1  2/50 (4.00%)  2/26 (7.69%) 
Musculoskeletal and connective tissue disorders     
Back Pain * 1  6/50 (12.00%)  2/26 (7.69%) 
Muscle Spasms * 1  1/50 (2.00%)  2/26 (7.69%) 
Myalgia * 1  3/50 (6.00%)  0/26 (0.00%) 
Pain in Extremity * 1  3/50 (6.00%)  4/26 (15.38%) 
Nervous system disorders     
Dizziness * 1  4/50 (8.00%)  2/26 (7.69%) 
Headache * 1  3/50 (6.00%)  1/26 (3.85%) 
Psychiatric disorders     
Insomnia * 1  2/50 (4.00%)  2/26 (7.69%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  2/50 (4.00%)  4/26 (15.38%) 
Dyspnoea * 1  4/50 (8.00%)  2/26 (7.69%) 
Vascular disorders     
Hypotension * 1  3/50 (6.00%)  0/26 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA Version 15.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: DIRECTOR CLINICAL RESEARCH
Organization: Janssen Research & Development
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01513317     History of Changes
Other Study ID Numbers: CR100752
CNTO328MDS2001 ( Other Identifier: Janssen Research & Development, LLC )
2011-000261-12 ( EudraCT Number )
First Submitted: October 21, 2011
First Posted: January 20, 2012
Results First Submitted: September 24, 2014
Results First Posted: September 29, 2014
Last Update Posted: September 29, 2014