ELRITERCEPT for Myelodysplastic syndrome | Anemia

Inclusion criteria

• {"criterion_text":"- Diagnosis of MDS (Parts 1 and 2) according to WHO classification that meets International Prognostic Scoring System-Revised (IPSS-R) classification of very low, low, or intermediate risk disease."}
• {"criterion_text":"- < 5% blasts in bone marrow during the Pretreatment Period."}
• {"criterion_text":"- Peripheral blood white blood cell (WBC) count < 13,000/μL during the Pretreatment Period."}
• {"criterion_text":"- Anemia defined as: A). In non-transfused participants, having received no RBC transfusions within 8 weeks, Hgb concentration ≤ 10.0 g/dL during the Pretreatment Period OR B).a. In LTB participants, having received 1 to 3 units of RBCs for Hgb ≤ 9.0 g/dL within 8 weeks of the Pretreatment Period OR C). In HTB participants, having received ≥ 4 units of RBCs for Hgb ≤ 9.0 g/dL within 8 weeks of the Pretreatment Period."}
• {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (if related to anemia)."}
• {"criterion_text":"- Females of child-bearing potential and sexually active males must agree to use highly effective methods of contraception."}

Exclusion criteria

• {"criterion_text":"- Active infection requiring parenteral antibiotic therapy within 28 days prior to C1D1 or oral antibiotics within 14 days of C1D1. Prophylactic antibiotics and/or antifungals for neutropenia are allowed."}
• {"criterion_text":"- Treatment history: Prior treatment with azacitidine, decitabine, lenalidomide, luspatercept, or sotatercept."}
• {"criterion_text":"- Treatment history: Treatment with ESA within 8 weeks prior to C1D1 (or C5D1 for the Part 1 Extension)."}
• {"criterion_text":"- Treatment history for part 2: Prior treatment with luspatercept (Cohorts A, B, C, D, E, and F only)"}
• {"criterion_text":"- Treatment history: Prior or concurrent chronic treatment with granulocyte colony stimulating factor (G-CSF) orgranulocyte-macrophage colony stimulating factor (GM-CSF), for reasons other than the treatment of MDS."}
• {"criterion_text":"- Platelet count > 450 x 10*9/L or < 30 x 10*9/L."}
• {"criterion_text":"- Transferrin saturation < 15%."}
• {"criterion_text":"- Ferritin < 50 μg/L."}
• {"criterion_text":"- Folate < 4.5 nmol/L (< 2.0 ng/mL)."}
• {"criterion_text":"- Vitamin B12 < 148 pmol/L (< 200 pg/mL)."}
• {"criterion_text":"- Estimated glomerular filtration rate (GFR) < 30 mL/min/1.73 m2 (as determined by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]."}
• {"criterion_text":"- Pregnant or lactating females."}
• {"criterion_text":"- For Cohort G ONLY (for part 2): 1. Any luspatercept related AE Grade ≥ 3 that has not resolved to baseline or Grade ≤1 2. No history of allergy/anaphylaxis/hypersensitivity to luspatercept. 3. No prior treatment with imetelstat."}
• {"criterion_text":"- Medical history: Diagnosis of MDS with deletion of chromosome 5q (Del5q)."}
• {"criterion_text":"- Medical history: Presence of uncontrolled heart disease or New York Heart Association Class III or IV heart failure."}
• {"criterion_text":"- Medical history: Presence of uncontrolled hypertension (Grade >/= 2 high blood pressure)."}
• {"criterion_text":"- Diagnosis of secondary MDS (ie, MDS that is known to have arisen as the result of chemical injury or treatment with chemotherapy and/or radiation for other diseases)."}
• {"criterion_text":"- Medical history: Any malignancy other than MDS that has not been in remission and/or has required systemictherapy 1 year prior to C1D1 (or C5D1 for the Part 1 Extension)."}
• {"criterion_text":"- Medical history: History of solid organ or hematological transplantation"}
• {"criterion_text":"- Medical history: Body mass index >/= 40 kg/m2 during the pretreatment period."}

Primary endpoints

• {"endpoint_text":"- Part 1 and Part 2: • Safety and tolerability as determined by the incidence of treatment emergent adverse events(TEAEs) and serious adverse events (SAEs).","definition_or_measurement_approach":"Determined by the incidence of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)."}
• {"endpoint_text":"- Long-term Extension: •Safety and tolerability as determined by the incidence of TEAEs and SAEs over time","definition_or_measurement_approach":"Determined by the incidence of TEAEs and SAEs over time."}

Secondary endpoints

• {"endpoint_text":"- Incidence of progression to higher risk MDS or AML per World Health Organization (WHO) 2016 criteria.","definition_or_measurement_approach":"Per World Health Organization (WHO) 2016 criteria."}
• {"endpoint_text":"- Proportion of low transfusion burden (LTB) and high transfusion burden (HTB) participants who achieve red blood cell (RBC) transfusion independence (TI) ≥ 8 weeks, overall and by RS status.","definition_or_measurement_approach":"Proportion achieving RBC transfusion independence (TI) ≥ 8 weeks, evaluated overall and by ring sideroblast (RS) status."}
• {"endpoint_text":"- Proportion of participants who achieve modified 2006 International Working Group (IWG) Hematologic Improvement-Erythroid (HI E) response overall and by RS status (See Table 3 in Protocol KER050-MD-201 v 7.0).","definition_or_measurement_approach":"Proportion achieving modified 2006 IWG Hematologic Improvement-Erythroid (HI-E) response, overall and by RS status (per protocol Table 3)."}
• {"endpoint_text":"- Efficacy Endpoint: Proportion of participants who achieve overall erythroid response, defined as either HI-E or TI over any 8-week period, overall and by RS status","definition_or_measurement_approach":"Proportion achieving either HI-E or transfusion independence (TI) over any 8-week period, overall and by RS status."}
• {"endpoint_text":"- Efficacy Endpoint: Proportion of participants who achieve erythropoietic improvement overall and by RS status (See Table 3 in Protocol KER050-MD-201 v 7.0).","definition_or_measurement_approach":"Proportion achieving erythropoietic improvement as defined in protocol Table 3, overall and by RS status."}
• {"endpoint_text":"- Efficacy Endpoint: Mean change from Baseline in Hgb by visit","definition_or_measurement_approach":"Mean change from baseline in hemoglobin (Hgb) measured at each visit."}
• {"endpoint_text":"- Efficacy Endpoint: Time to HI-E response.","definition_or_measurement_approach":"Time from baseline to attainment of HI-E response."}
• {"endpoint_text":"- Efficacy Endpoint: Duration of HI-E response.","definition_or_measurement_approach":"Duration (time) of HI-E response from onset to loss of response per protocol definitions."}
• {"endpoint_text":"- Efficacy Endpoint: Time to TI response.","definition_or_measurement_approach":"Time from baseline to transfusion independence (TI) response."}
• {"endpoint_text":"- Efficacy Endpoint: Time to TI response.","definition_or_measurement_approach":"Time from baseline to transfusion independence (TI) response."}
• {"endpoint_text":"- Efficacy Endpoint: Proportion of LTB and HTB participants who achieve TI ≥ 12 weeks, 16 weeks, 24 weeks, 48 weeks.","definition_or_measurement_approach":"Proportion of participants in LTB and HTB groups achieving TI at specified durations (≥12, 16, 24, 48 weeks)."}
• {"endpoint_text":"- Proportion of LTB and HTB participants who achieve TI ≥ 12 weeks, 16 weeks, 24 weeks, 48 weeks.","definition_or_measurement_approach":"Proportion achieving transfusion independence at specified durations (≥12, 16, 24, 48 weeks)."}
• {"endpoint_text":"- Pharmacodynamic Endpoint: Change from baseline of red cell parameters, including reticulocyte count, mean corpuscular volume, mean corpuscular hemoglobin, and reticulocyte cell Hgb by visit.","definition_or_measurement_approach":"Change from baseline in specified red cell parameters measured by laboratory assays at visits."}

Czechia

Latest Decision Or Authorization Date

17-09-2024

Number Of Sites

1

Number Of Participants

2

Germany

Latest Decision Or Authorization Date

20-09-2024

Number Of Sites

8

Number Of Participants

18

Spain

Latest Decision Or Authorization Date

16-09-2024

Number Of Sites

5

Number Of Participants

27

France

Latest Decision Or Authorization Date

20-09-2024

Number Of Sites

5

Number Of Participants

9

Primary sponsor

Full Name

Takeda Development Center Americas Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

4g Clinical LLC

Responsibilities

code: 3

Name

IQVIA Limited

Responsibilities

codes: 1,12,2,6,8

Name

Q Squared Solutions Limited

Responsibilities

Routine clinical pathology testing, clinical chemistry, clinical haematology, histopathology, serology/endocrinology, analytical chemistry, PK/ADA sample analysis and antidrug antibody

Name

Q Squared Solutions LLC

Responsibilities

OPG and RANKL

Name

Almac Clinical Services LLC

Responsibilities

code: 14

Name

Pharmaron (US) Clinical Services Inc.

Responsibilities

code: 10

Third parties

• {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"code: 3","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Almac Clinical Services LLC","duties_or_roles":"code: 14","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Universitaet Leipzig","duties_or_roles":"Analysis of peripheral blood/bone marrow","organisation_type":"Educational Institution"}
• {"country":"Australia","full_name":"360 Biolabs Pty Limited","duties_or_roles":"PK, ADA and Hepcidin","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"Routine clinical pathology testing, clinical chemistry, clinical haematology, histopathology, serology/endocrinology, analytical chemistry, PK/ADA sample analysis and antidrug antibody","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Q Squared Solutions LLC","duties_or_roles":"OPG and RANKL","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"codes: 1,12,2,6,8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Azenta US Inc.","duties_or_roles":"Long term sample storage","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"Cardiac biomarkers","organisation_type":"Pharmaceutical company"}
• {"country":"Sweden","full_name":"Viedoc Technologies AB","duties_or_roles":"code: 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Almac Clinical Services LLC (Durham address)","duties_or_roles":"code: 14","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Pharmaron (US) Clinical Services Inc.","duties_or_roles":"code: 10","organisation_type":"Pharmaceutical company"}