Anemia, Bone Marrow Disease, MDS, Myelodysplastic Syndromes
Conditions
Keywords
MDS, HS-20106, KER-050, fusion protein, TGF-β
Brief summary
The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics of HS-20106 on anemia in patients with very low, low or intermediate risk MDS.
Detailed description
Anemia is considered to be one of the most prevalent cytopenias in patients who have myelodysplastic syndromes, an umbrella term used to describe disorders relating to the ineffective production of red blood cells, white blood cells, and/or platelets. The goal of this study is to assess the efficacy, safety and PK of HS-20106 on anemia in Chinese patients with very low, low or intermediate risk MDS. Eligible subjects will be treated with HS-20106. Patients should be treated for at least 24 weeks in the core treatment period to assess their response to treatment.
Interventions
DRUGHS-20106
HS-20106 administered subcutaneously every 4 weeks for up to 6 cycles. Eligible participants may be able to continue to receive subcutaneously administered HS-20106 after completing 6 cycles in the extended treatment period.
Sponsors
Hansoh BioMedical R&D Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of MDS according to World Health Organization (WHO) classification that meets Revised International Prognostic Scoring System (IPSS-R) classification of very low, low, or intermediate risk disease（IPSS-R ≤ 3.5）. 2. \< 5% blasts in bone marrow and \< 1% blasts in peripheral blood. 3. Each cohort is defined as: Cohort 1： In NTD participants, having received no red blood cell (RBC) transfusions within 16 weeks Hgb concentration between 60 and 100g/L. Cohort 2： In LTB participants, having received an average of \< 4 units of RBC transfused within 8 weeks (i.e., total blood transfused over 16 weeks/2) Hgb concentration between 60 and 100 g/L. In HTB participants, having received an average of ≥ 4 units of RBC transfused within 8 weeks (i.e., total blood transfused over 16 weeks/2) Hgb concentration between 60 and 100 g/L. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (if related to anemia. 5. Females of child-bearing potential and sexually active males must agree to use effective methods of contraception.
Exclusion criteria
1. Chromosome 5q deletion, del (5q). 2. Anemia caused by other reasons, such as iron deficiency anemia, megaloblastic anemia, aplastic anemia, renal anemia or blood loss. 3. Diagnosis of secondary MDS (i.e., MDS known to have arisen as the result of chemical injury or treatment with chemotherapy and/or radiation for other diseases). 4. Prior treatment with azacitidine, decitabine, lenalidomide, luspatercept, or sotatercept. 5. Treatment within 4 weeks prior to C1D1 with: 1\) Erythropoiesis stimulating agent (ESA) OR 2) Granulocyte colony-stimulating factor (G-CSF) OR 3) Granulocyte-macrophage colony-stimulating factor (GM-CSF) 6. Iron chelation therapy if initiated within 8 weeks prior to C1D1. 7. Vitamin B12 therapy if initiated within 8 weeks prior to C1D1. 8. Treatment with another investigational drug or device or approved therapy for investigational use \< or = 4 weeks prior to C1D1, or if the half-life of the previous product is known, within 5 times the half-life prior to C1D1, whichever is longer. 9\. Peripheral blood white blood cell count \>13.0 x 10\*9/L. 10. Neutrophil count \< 1.0 x 10\*9/L. 11. Platelet count \> 450 x 10\*9/L or \< 30 x 10\*9/L. 12. Transferrin saturation \< 15%. 13. Ferritin \< 15 μg/L. 14. Folate \< 4.5 nmol/L (\< 2.0 ng/mL). 15. Vitamin B12 \< 148 pmol/L (\< 200 pg/mL). 16. Estimated glomerular filtration rate (GFR) \< 40 mL/min/1.73 m2 (as determined by the Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\]. 17\. Pregnant or lactating females
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants who achieve modified 2006 International Working Group (IWG)Hematologic Improvement-Erythroid (HI-E) response | Week 1 through Week 24 | * In NTD and LTB participants, response is defined as a mean hemoglobin (Hgb) increase of ≥ 15 g/L from Baseline during any consecutive 8-week period during the treatment period (in the absence of RBC transfusions) * In HTB participants, response is defined as a reduction by ≥ 4 units of RBCs transfused during any consecutive 8-week period on study compared with Baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to HI-E | Week 1 through Week 24 | the time from the first dose of study drug to the first achievement of HI-E. |
| Proportion of participants with RBC-TI ≥ 8 Weeks（cohort 2 only） | Week 1 through Week 24 | the proportion of participants who did not require RBC transfusion for at least 1 consecutive 8-week period. |
| Duration of TI response | Throughout the study period, assessed up to 48 weeks. | the longest duration of response for participants who achieved RBC-TI of ≥ 8 weeks during the treatment period |
| Time to RBC-TI ≥ 8 weeks | Week 1 through Week 24 | the time from the first dose of study drug to the first achievement of RBC-TI ≥ 8 weeks. |
| The proportion of participants with progression to intermediate-risk (IPSS-R score > 3.5) and higher MDS or AML. | Week 1 through Week 24 | Percentage of participants progressing to intermediate-risk (IPSS-R score \> 3.5) or higher MDS or AML throughout the course of the study |
| HI-E Duration | Throughout the study period, assessed up to 48 weeks. | the maximum duration of meeting the HI-E criteria for a subject who achieved HI-E. |
| Incidence of adverse events (AEs) and serious adverse events (SAEs). | Throughout the study period, assessed up to 48 weeks. | Type, frequency, severity of AEs and relationship of AEs to HS-20106 |
| Pharmacokinetic- AUC | Throughout the study period, assessed up to 48 weeks. | Pharmacokinetics of HS-20106 |
| Pharmacokinetic- Cmax | Throughout the study period, assessed up to 48 weeks. | Maximum plasma concentration of drug |
| Antidrug antibodies (ADA) | Throughout the study period, assessed up to 48 weeks. | Frequency of antidrug antibodies and effects on efficacy, safety or PK |
| Time to progression to intermediate-risk (IPSS-R score > 3.5) or higher MDS or AML. | Week 1 through Week 24 | Time to progression was defined as the time between the first dose date and the first diagnosis of progression. |
Countries
China
Contacts
Primary ContactZhijian Xiao, PhD
Outcome results
None listed