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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04810611




Registration number
NCT04810611
Ethics application status
Date submitted
9/03/2021
Date registered
23/03/2021
Date last updated
17/05/2024

Titles & IDs
Public title
Phase Ib Study of Select Drug Combinations in Patients With Lower Risk MDS
Scientific title
A Phase Ib, Multicenter, Open-label Platform Study of Select Drug Combinations in Adult Patients With Lower Risk (Very Low, Low, or Intermediate Risk) Myelodysplastic Syndrome
Secondary ID [1] 0 0
2019-004623-21
Secondary ID [2] 0 0
CMBG453E12101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myelodysplastic Syndromes 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - MBG453
Treatment: Drugs - NIS793
Treatment: Drugs - canakinumab

Experimental: Arm 1: MBG453 single agent - Treatment with MBG453 single agent Q4W to confirm safety and tolerability of RD.

Experimental: Arm 2: NIS793 single agent - Treatment with NIS793 single agent Q3W to establish RD in this indication and confirm safety and tolerability.

Experimental: Arm 3: canakinumab single agent - Treatment with single agent canakinumab Q4W to confirm safety and tolerability of RD.

Experimental: Arm 4: MBG453 + NIS793 combination - Treatment with combination of MBG453 and NIS793 Q3W to confirm safety and tolerability of combination RD.

Experimental: Arm 5: MBG453 + canakinumab combination - Treatment with MBG453 + canakinumab combination Q4W to confirm safety and tolerability of combination RD.


Treatment: Drugs: MBG453
Anti-TIM3 monoclonal antibody

Treatment: Drugs: NIS793
Anti-TGF-ß monoclonal antibody

Treatment: Drugs: canakinumab
Anti-IL-1ß monoclonal antibody
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose interruption reduction
Timepoint [1] 0 0
30 Months
Primary outcome [2] 0 0
Incidence of DLTs
Timepoint [2] 0 0
30 Months
Primary outcome [3] 0 0
Dose intensity
Timepoint [3] 0 0
30 Months
Primary outcome [4] 0 0
AE and SAE incidence
Timepoint [4] 0 0
30 months
Secondary outcome [1] 0 0
Reduction in red blood cell (RBC) / platelet transfusions from baseline in transfusion dependent patients
Timepoint [1] 0 0
Baseline, 30 Months
Secondary outcome [2] 0 0
Duration of transfusion independence lasting for >=8 weeks, >=12 weeks, >=16 weeks, >=24 weeks in transfusion dependent patients
Timepoint [2] 0 0
30 Months
Secondary outcome [3] 0 0
Change from baseline in hemoglobin (Hb) in transfusion dependent and transfusion independent patients
Timepoint [3] 0 0
Baseline, 30 Months
Secondary outcome [4] 0 0
Change from baseline in platelet count in transfusion dependent and transfusion independent patients
Timepoint [4] 0 0
Baseline, 30 Months
Secondary outcome [5] 0 0
Change from baseline in Absolute Neutrophil Count/White Blood Cells (ANC/WBC) in transfusion dependent and transfusion independent patients
Timepoint [5] 0 0
Baseline, 30 Months
Secondary outcome [6] 0 0
Best Overall Response (BOR) in transfusion dependent and transfusion independent patients
Timepoint [6] 0 0
30 Months
Secondary outcome [7] 0 0
Time to onset of transfusion independence in transfusion dependent patients
Timepoint [7] 0 0
30 Months
Secondary outcome [8] 0 0
Time to onset of BOR in transfusion dependent and transfusion independent patients
Timepoint [8] 0 0
30 Months
Secondary outcome [9] 0 0
Duration of Response (DOR) in transfusion dependent and transfusion independent patients
Timepoint [9] 0 0
30 Months
Secondary outcome [10] 0 0
Overall Response Rate (ORR) in transfusion dependent and transfusion independent patients
Timepoint [10] 0 0
30 Months
Secondary outcome [11] 0 0
Progression free survival (PFS) in transfusion dependent and transfusion independent patients
Timepoint [11] 0 0
30 Months
Secondary outcome [12] 0 0
Time to progression (TTP) in transfusion dependent and transfusion independent patients
Timepoint [12] 0 0
30 Months
Secondary outcome [13] 0 0
Characterize pharmacokinetics for single agents and combinations: Cmax
Timepoint [13] 0 0
30 Months
Secondary outcome [14] 0 0
Characterize pharmacokinetics for single agents and combinations: Tmax
Timepoint [14] 0 0
30 Months
Secondary outcome [15] 0 0
Characterize pharmacokinetics for single agents and combinations: Ctrough
Timepoint [15] 0 0
30 Months
Secondary outcome [16] 0 0
Characterize the prevalence of immunogenicity
Timepoint [16] 0 0
30 Months

Eligibility
Key inclusion criteria
Key

1. Signed informed consent must be obtained prior to participation in the study.
2. Patients must be = 18 years of age at the time of signing the informed consent form (ICF).
3. Patients must have a diagnosis prior to participation in the study of IPSS-R very low, low, or intermediate risk MDS with =10% bone marrow blasts and one or more of the following:

1. Symptomatic anemia with hemoglobin <10 g/dL that has relapsed after or is refractory to ESAs (or the patient is intolerant to ESAs)
2. Symptomatic anemia with hemoglobin <10 g/dL) that is ESA-naive with EPO level = 500 /uL
3. Thrombocytopenia with platelets <30,000/uL or with clinically significant bleeding or bruising and platelets <50,000/uL
4. Neutropenia with an absolute neutrophil count (ANC) <500/ µL or with recurrent and/or severe infections and an ANC that is <1000/ µL and amenable to response assessments by International Working Group (IWG) response criteria in myelodysplasia (Cheson et al 2006)
4. Patients who are refractory to, intolerant of, or ineligible/unable to receive SOC therapeutic options including lenalidomide
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) =2
6. Patient must be a candidate for serial bone marrow aspirate and/or biopsy according to the institutions' guidelines and be willing to undergo a bone marrow aspirate and/or biopsy at screening, during and at the end of therapy on this study -

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Systemic antineoplastic therapy (including cytotoxic chemotherapy, alpha-interferon, kinase inhibitors or other targeted small molecules, and toxin-immunoconjugates) or any experimental therapy within 14 days or 5 half-lives, whichever is longer, before the first dose of study treatment.
2. History of hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes.
3. Patients with chronic myelomonocytic leukemia (CMML) or myelodysplastic/myeloproliferative neoplasms (MDS/MPN)
4. Use of hematopoietic colony-stimulating growth factors (e.g. G-CSF, GM-CSF, M-CSF), thrombopoietin mimetics or ESAs anytime = 2 weeks (or 5 half-lives, whichever is longer) prior to start of study treatment.
5. Systemic chronic corticosteroid therapy (>10 mg/day prednisone or equivalent) or any immunosuppressive therapy within 7 days of first dose of study treatment. Topical, inhaled, nasal and ophthalmic steroids are allowed.
6. For arms containing canakinumab: Patients with ANC < 500 /µL

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/06/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
19/04/2024
Sample size
Target
Accrual to date
Final
33
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Prahran
Recruitment postcode(s) [1] 0 0
3181 - Prahran
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
Ohio
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
Israel
State/province [6] 0 0
Tel Aviv
Country [7] 0 0
Italy
State/province [7] 0 0
MI
Country [8] 0 0
Korea, Republic of
State/province [8] 0 0
Seoul
Country [9] 0 0
Singapore
State/province [9] 0 0
Singapore
Country [10] 0 0
Spain
State/province [10] 0 0
Castilla Y Leon
Country [11] 0 0
Spain
State/province [11] 0 0
Catalunya

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study was to characterize the safety, tolerability and confirm the dose for select single agents and combinations in patients with lower risk (very low, low, and intermediate risk) MDS.
Trial website
https://clinicaltrials.gov/study/NCT04810611
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04810611