A Study of HS-20106 to Treat Anemia Due to Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes

Phase II Study on the Efficacy, Safety, and Pharmacokinetics of HS-20106 in Patients With IPSS-R Very Low-risk, Low-risk, or Moderate-risk Myelodysplastic Syndrome (MDS) Anemia

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Myelodysplastic Syndromes; Anemia; MDS; Bone Marrow Disease
• Intervention / Treatment: Drug: HS-20106

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.

• Study Type: Interventional
• Enrollment (Estimated): 176
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhijian Xiao, PhD; Phone Number: (0086)022-23909184; Email: xiaozj_mds026@163.com

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China
      • Institute of Hematology and Blood Diseases Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HS-20106 Cohort 1; Part A: Non-transfusion dependent population	Drug: HS-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.
Experimental: HS-20106 Cohort 2; Part A: Transfusion-Dependent Population（low-transfusion burden (LTB) and high-transfusion burden (HTB)）	Drug: HS-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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants who achieve modified 2006 International Working Group (IWG)Hematologic Improvement-Erythroid (HI-E) response	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	Week 1 through Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HI-E Duration	the maximum duration of meeting the HI-E criteria for a subject who achieved HI-E.	Throughout the study period, assessed up to 48 weeks.
Time to HI-E	the time from the first dose of study drug to the first achievement of HI-E.	Week 1 through Week 24
Proportion of participants with RBC-TI ≥ 8 Weeks（cohort 2 only）	the proportion of participants who did not require RBC transfusion for at least 1 consecutive 8-week period.	Week 1 through Week 24
Duration of TI response	the longest duration of response for participants who achieved RBC-TI of ≥ 8 weeks during the treatment period	Throughout the study period, assessed up to 48 weeks.
Time to RBC-TI ≥ 8 weeks	the time from the first dose of study drug to the first achievement of RBC-TI ≥ 8 weeks.	Week 1 through Week 24
The proportion of participants with progression to intermediate-risk (IPSS-R score > 3.5) and higher MDS or AML.	Percentage of participants progressing to intermediate-risk (IPSS-R score > 3.5) or higher MDS or AML throughout the course of the study	Week 1 through Week 24
Time to progression to intermediate-risk (IPSS-R score > 3.5) or higher MDS or AML.	Time to progression was defined as the time between the first dose date and the first diagnosis of progression.	Week 1 through Week 24
Incidence of adverse events (AEs) and serious adverse events (SAEs).	Type, frequency, severity of AEs and relationship of AEs to HS-20106	Throughout the study period, assessed up to 48 weeks.
Pharmacokinetic- AUC	Pharmacokinetics of HS-20106	Throughout the study period, assessed up to 48 weeks.
Pharmacokinetic- Cmax	Maximum plasma concentration of drug	Throughout the study period, assessed up to 48 weeks.
Antidrug antibodies (ADA)	Frequency of antidrug antibodies and effects on efficacy, safety or PK	Throughout the study period, assessed up to 48 weeks.

Collaborators and Investigators

• Sponsor: Hansoh BioMedical R&D Company

Study record dates

Study Major Dates

• Study Start (Estimated): October 30, 2024
• Primary Completion (Estimated): October 30, 2025
• Study Completion (Estimated): October 30, 2026

Study Registration Dates

• First Submitted: September 10, 2024
• First Submitted That Met QC Criteria: September 10, 2024
• First Posted (Estimated): September 13, 2024

Study Record Updates

• Last Update Posted (Estimated): September 19, 2024
• Last Update Submitted That Met QC Criteria: September 14, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: MDS; TGF-β; fusion protein; HS-20106; KER-050
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia; Anemia; Bone Marrow Diseases
• Other Study ID Numbers: HS-20106-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No