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

• Register: EUCTR
• Last refreshed on: 21 August 2017
• Main ID: EUCTR2011-000261-12-BE
• Date of registration: 27/06/2011
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International N.V.
• Public title: A Study Comparing Siltuximab Plus Best Supportive Care to Placebo Plus Best Supportive Care in Anemic Subjects with International Prognostic Scoring System Low- or Intermediate-1-Risk Myelodysplastic Syndrome
• Scientific title: A Phase 2, Randomized, Double-blind, Placebo-controlled, Multicenter Study Comparing Siltuximab Plus Best Supportive Care to Placebo Plus Best Supportive Care in Anemic Subjects with International Prognostic Scoring System Low- or Intermediate-1-Risk Myelodysplastic Syndrome
• Date of first enrolment: 28/09/2011
• Target sample size: 75
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-000261-12
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: Open; study will continue until death, unacceptable toxicity, withdraw consent, or clinical cutoff If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Netherlands, Russian Federation, Spain, Sweden, United States

Contacts

• Name: Clinical Registry Group
• Affiliation: Janssen-Cilag International N.V.

• Name: Clinical Registry Group
• Affiliation: Janssen-Cilag International N.V.

Key inclusion & exclusion criteria

Inclusion criteria:
-Confirmed diagnosis of myelodysplastic syndrome (MDS), according to World Heath Organization or the French-American-British Cooperative Group pathologic classification, with an International Prognostic Scoring System score 0, 0.5, or 1.0, indicating Low- or INT-1-risk disease.
- Documented RBC transfusion of at least 2 units of RBC for the treatment of the anemia of MDS in the 8 weeks preceding the start of the Screening Period. - Adequate iron stores, demonstrated by either the presence of stainable iron in the bone marrow or a serum ferritin of > 100 ng/mL.
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2.
- Symptomatic anemia (defined by a score > 0 on the Non-Chemotherapy Anemia Symptom Scale [NCA-SS]).
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 25
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion criteria:
- Had treatment with drugs or other agents targeting IL-6 or its receptor within 4 weeks of randomization.
- Any condition that, in the opinion of the investigator, would make participation not in the best interest (eg, compromise the well-being) of the patient or that could prevent, limit, or confound the protocol-specified assessments.
- Patients with Chronic Myelomonocytic Leukemia (CMML).
- Causes other than MDS contributing to anemia, such as Vitamin B12 or folate deficiency, bleeding, hemolysis, hemoglobinopathy, or chronic renal failure.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Anemia associated with Low- or Intermediate-1-Risk Myelodysplastic Syndrome
MedDRA version: 14.1 Level: LLT Classification code 10028534 Term: Myelodysplastic syndrome NOS System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1 Level: LLT Classification code 10002272 Term: Anemia System Organ Class: 10005329 - Blood and lymphatic system disorders

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: Siltuximab
Product Code: CNTO328
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Siltuximab
Current Sponsor code: CNTO328
Other descriptive name: Chimeric murine human anti-IL-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 400-
Pharmaceutical form of the placebo: Powder for solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Secondary Objective: • To demonstrate symptomatic improvement of subjects treated with siltuximab compared with the placebo group
• To compare the number of RBC units transfused to treat the anemia of MDS, and the proportion of subjects treated with siltuximab who do not require a RBC transfusion to treat the anemia of MDS, from Week 5 to Week 12, compared with the placebo group
• To assess the change in hemoglobin among MDS subjects treated with siltuximab compared with the placebo group
• To compare disease progression (proportion of bone marrow blasts and cytogenetic change) for subjects treated with siltuximab compared with the placebo group
• To assess the safety profile of siltuximab and RBC transfusions among subjects with Low- or Intermediate-1 (INT-1)-risk MDS
• To assess the pharmacodynamics, pharmacokinetics, and antibodies to siltuximab (immunogenicity) in MDS subjects
•See protocol for additional objectives

Primary end point(s): Proportion of patients achieving a reduction in RBC transfusions

Main Objective: The primary objective is to assess the clinical efficacy of siltuximab,
demonstrated by a reduction in RBC transfusions to treat the anemia of
MDS.

Timepoint(s) of evaluation of this end point: 8 week period from week 5 to week 12

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. At Week 12
2. At Week 13 and every 24 weeks during treatment
3. Daily for 12 weeks, then monthly for remainder of treatment period

Secondary end point(s): 1. Hemoglobin Assessment
2. Bone Marrow Examination
3. Anemia Symptom Assessment

Secondary ID(s)

CNTO328MDS2001

Source(s) of Monetary Support

Janssen Research & Development