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: 22 October 2012
• Main ID: EUCTR2011-000261-12-NL
• Date of registration: 31/08/2011
• 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: 06/01/2012
• 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

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:
1. At least 18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place)
2. Confirmed diagnosis of MDS, according to WHO or FAB pathologic
classification, with an IPSS score 0, 0.5, or 1.0, indicating Low- or INT-1-
risk disease. Subjects with 5q- or PDGFR gene mutations are eligible if
they are intolerant to or have failed prior specific therapy (eg,
lenalidomide and imatinib mesylate).
3. 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.
4. Adequate iron stores, demonstrated by either the presence of
stainable iron in the bone marrow or a serum ferritin of > 100 ng/mL
5. ECOG performance status score of 0 to 2
6. Symptomatic anemia (defined by a score > 0 on the NCA-SS).
7. Women of childbearing potential must agree to use adequate birth
control measures during the study and for 3 months after receiving the
last dose of study agent, and have a negative serum or urine beta human
chorionic gonadotropin (beta hCG) pregnancy test at screening. Men
must agree to use a double barrier method of birth control and to not
donate sperm during the study and for 3 months after receiving the last
dose of study agent
8.Be willing and able to adhere to the prohibitions and restrictions
specified in this protocol
9.Sign (or their legally acceptable representatives must sign) an
informed consent document indicating that they understand the purpose
of and procedures required for the study and are willing to participate in
the study.
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:
1.Had treatment with ESAs, androgens, hypomethylating agents,
immunomodulatory drugs (IMiDs), or other agents targeting IL-6 or its
receptor within 4 weeks of randomization
2.Any condition that, in the opinion of the investigator, would make
participation not be in the best interest (eg, compromise the well-being)
of the subject or that could prevent, limit, or confound the protocolspecified
assessments (eg, has a history of clinically significant,
uncontrolled disease of the pulmonary, cardiovascular, endocrine,
neurologic, gastrointestinal, or genitourinary systems that is not
attributable to MDS). Subjects with Chronic Myelomonocytic Leukemia
(CMML) are to be excluded from the study.
3.Causes other than MDS contributing to anemia, such as Vitamin B12 or
folate deficiency, bleeding, hemolysis, hemoglobinopathy, or chronic
renal failure
4.Known unmanageable allergies, hypersensitivity, or intolerance to
monoclonal antibodies or to murine, chimeric, or human proteins or their
excipients
5.A history of seropositivity for human immunodeficiency virus (HIV),
hepatitis B virus (HBV), or hepatitis C virus (HCV) (Note: HBV antibodypositivity
is not a reason for exclusion from the study)
6.Received an investigational drug (including investigational vaccines)
or used an invasive investigational medical device within 30 days or 5
half lives before randomization or is currently enrolled in an
investigational study
7.Had a modification of an effective preexisting therapy for the explicit
purpose of entering the study.
8.Is a woman who is pregnant, or breast-feeding, or planning to become
pregnant or is a man who plans to father a child while enrolled in this
study or within 12 weeks after the last dose of study agent
9.Had hospitalization for infection or major surgery, (eg, requiring
general anesthesia) within 2 weeks before randomization or will not
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have fully recovered from surgery.
Note: subjects with planned surgical procedures to be conducted under
local anesthesia may participate
10.Been vaccinated with live, attenuated vaccines within 4 weeks of
randomization
11.Has clinically significant laboratory abnormalities:
•Platelets < 20 x 109/L
•Estimated glomerular filtration rate (eGFR) <=20 mL/min
•Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =
2.5 x upper limit of normal (ULN)
•Bilirubin > 2.5 x ULN
•Alkaline phosphatase = 3 x ULN
12.Is an employee of the investigator or study site, with direct
involvement in the proposed study or other studies under the direction
of that investigator or study site, as well as family members of the
employees or the investigator
NOTE: Investigators should ensure that all study enrollment criteria
have been met at screening. If a subject's status (including laboratory
results) changes after screening but before the first dose of study agent
is given such that they now meet an exclusion criterion, then they should
be excluded from participation in the study.


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: 14.0 Level: LLT Classification code 10028534 Term: Myelodysplastic syndrome NOS System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.0 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)

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.

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

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

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

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)

2011-000261-12-BE

CNTO328MDS2001

Source(s) of Monetary Support

Janssen Research & Development