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Trial registered on ANZCTR


Registration number
ACTRN12620000696998
Ethics application status
Approved
Date submitted
7/05/2020
Date registered
22/06/2020
Date last updated
22/06/2020
Date data sharing statement initially provided
22/06/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 2, Open-Label, Ascending Dose Study of KER-050 for the Treatment of Anemia in Patients with Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MDS)
Scientific title
A Phase 2, Open-Label, Ascending Dose Study of KER-050 for the Treatment of Anemia in Patients with Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MDS)
Secondary ID [1] 301093 0
KER050-MD-201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myelodysplastic Syndromes 317165 0
Condition category
Condition code
Blood 315317 315317 0 0
Anaemia
Blood 315318 315318 0 0
Haematological diseases
Blood 315319 315319 0 0
Normal development and function of platelets and erythrocytes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants in all cohorts will receive Investigational Medicinal Product (IMP) KER-050, administered subcutaneously (SC), every 4 weeks for up to 4 cycles, through Week 13.

The study contains two parts:
Part 1 Dose Escalation will consist of 4 cohorts ranging from a proposed dose level of .75 mg/kg to 3.75 mg/kg in approximately 6 participants per cohort.
Part 2 Dose Confirmation will consist of a single cohort at a dose level to be determined based on Part 1 in approximately 18-30 participants.

The study is open label, sequentially assigning participants to cohorts.
Intervention code [1] 317402 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 323570 0
Evaluate safety and tolerability of KER-050 in participants with very low, low, or intermediate risk MDS.

To be assessed by monitoring
• Incidence and severity of AE;
• Incidence of serious adverse events (SAE) and suspected unexpected serious adverse reactions;
• Clinically significant changes from baseline in:
- Laboratory evaluations (hematology, chemistry, urinalysis, urine collection, coagulation, lipid profile tests);
- Electrocardiograms (ECG);
- Vital signs;
- Physical examinations;
- Eastern Cooperative Oncology Group (ECOG) Performance Status;
- Anti-drug antibody.
Timepoint [1] 323570 0
Monitored from time of signing informed consent throughout the course of the study through Day 183.
Primary outcome [2] 323872 0
Progression to higher-risk MDS/AML. Assessed based on progression to AML as per WHO classification, further confirmatory histology or cytology results, etc. may be requested.
Timepoint [2] 323872 0
Assessed at screening, Day 99 and Day 183.
Secondary outcome [1] 382291 0
Maximum concentrations of KER-050. Assessments based on non-compartmental analyses will be conducted including summary statistics across individuals (number of participants, arithmetic mean, geometric mean, coefficient of variation, standard deviation, median, minimum and maximum) for specific PK measurements will be produced by dose level and time window.
Timepoint [1] 382291 0
PK is assessed at the following timepoints during the study: Days 1, 22, 29, 43, 57, 71, 85, and 99.
Secondary outcome [2] 382292 0
Erythroid response in low-transfusion-burden (LTB) and high-transfusion-burden (HTB).

Assessed in LTB participants, the proportion of participants who have a hemoglobin increase of greater than or equal to 1.5 g/dL from Baseline for greater than or equal to 14 days (in the absence of RBC transfusions) and in HTB participants, the proportion of participants having a reduction of greater than or equal to 50% or by greater than or equal to 4 RBC units transfused compared to pretreatment over an 8-week period.
Timepoint [2] 382292 0
Assessed from screening throughout the course of the study at Days 1, 8, 15, 22, 29, 43, 57, 71, 85, 99, every 2 weeks from Day 127 to 155, and at end of study Day 183.
Secondary outcome [3] 383112 0
Modified 2006 International Working Group (IWG) Hematologic Improvement Erythroid (HI-E) response.

Assessed in LTB participants, the proportion of participants with an increase of greater thank or equal to 1.5 g/dL from pretreatment hemoglobin during any 8-week period on study compared to Baseline and in HTB participants, the proportion of participants having a reduction by greater than or equal to 4 units of RBCs transfused (for a hemoglobin less than or equal to 9.0 g/dL) during any 8-week period on study, compared with the 8-week period prior to study Cycle 1 Day 1.
Timepoint [3] 383112 0
Assessed from screening throughout the course of the study at Days 1, 8, 15, 22, 29, 43, 57, 71, 85, 99, every 2 weeks from Day 127 to 155, and at end of study Day 183.
Secondary outcome [4] 383113 0
Mean change in hemoglobin. Assessed by change from baseline in hemoglobin, change from baseline in RBC and change from baseline in reticulocytes.
Timepoint [4] 383113 0
Assessed from screening throughout the course of the study at Days 1, 8, 15, 22, 29, 43, 57, 71, 85, 99, every 2 weeks from Day 127 to 155, and at end of study Day 183.
Secondary outcome [5] 383134 0
Frequency of RBC transfusions and rate of RBC transfusion independence. Assessed by greater than or equal to 8 weeks of transfusion independence.
Timepoint [5] 383134 0
Assessed from baseline through end of study Day 183.

Eligibility
Key inclusion criteria
1. Male or female > or = 18 years of age, at the time of signing informed consent.
2. Diagnosis of MDS according to World Health Organization (WHO)/French American British (FAB) classification that meets Revised International Prognostic Scoring System (IPSS-R) classification of very low, low, or intermediate risk disease.
3. < 5% blasts in bone marrow.
4. Peripheral blood white blood cell (WBC) count < 13,000/µL.
5. Anemia defined as:
- In LTB participants (defined as having received < 4 units of RBCs within 8 weeks), mean hemoglobin concentration < 10.0 g/dL of two measurements (one performed within 1 day prior to Cycle 1 Day 1 and the other performed 7-28 days prior, not influenced by RBC transfusion within 7 days of measurement) OR
- In HTB participants (defined as requiring > or = 4 units of RBCs for hemoglobin < or = 9.0 g/dL within 8 weeks)
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (if related to anemia).
7. Females of child-bearing potential and sexually active males must agree to use effective methods of contraception.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Any active infection requiring parenteral antibiotic therapy within 28 days prior to Cycle 1 Day 1 or oral antibiotics within 14 days of Cycle 1 Day 1.
2. 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).
3. Vitamin B12 deficiency.
4. Prior treatment with azacitidine, decitabine, lenalidomide, luspatercept, or sotatercept.
5. Treatment within 28 days prior to Cycle 1 Day 1 with:
a. Erythropoiesis stimulating agent (ESA) OR
b. Granulocyte colony-stimulating factor (G-CSF) OR
c. Granulocyte-macrophage colony-stimulating factor (GM-CSF)
6. Iron chelation therapy if initiated within 8 weeks prior to Cycle 1 Day 1.
7. Vitamin B12 therapy within 8 weeks prior to Cycle 1 Day 1.
8. Treatment with another investigational drug or device or approved therapy for investigational use < or = 28 days prior to Cycle 1 Day 1, or if the half-life of the previous product is known, within 5 times the half-life prior to Cycle 1 Day 1, whichever is longer.
9. Platelet count > 450 x 10*9/L or < 30 x 10*9/L.
10. Transferrin saturation < 15%.
11. Ferritin < 50 µg/L.
12. Folate < 4.5 nmol/L (< 2.0 ng/mL).
13. Vitamin B12 < 148 pmol/L (< 200 pg/mL).
14. Estimated glomerular filtration rate (GFR) < 60 mL/min/1.73 m2 (as determined by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI].
15. Pregnant or lactating females.

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)
Allocation is not concealed
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
Other
Other design features
Part 1 Dose Escalation
Part 2 Dose Confirmation (Single Group)

Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Adverse events (AEs) will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). The number and percentage of participants with treatment-emergent AEs and number of events will be summarized by system organ class and by preferred term. Treatment-emergent AEs by severity and relationship to the study drug will be summarized. Treatment-emergent SAEs and treatment-emergent AEs leading to premature discontinuation will also be summarized.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 16559 0
Ballarat Oncology and Haematology Services - Wendouree
Recruitment hospital [2] 16561 0
Border Medical Oncology - Albury
Recruitment hospital [3] 16562 0
Box Hill Hospital - Box Hill
Recruitment hospital [4] 16563 0
The Tweed Hospital - Tweed Heads
Recruitment hospital [5] 16566 0
Flinders Private Hospital - Bedford Park
Recruitment hospital [6] 16567 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 30126 0
2485 - Tweed Heads
Recruitment postcode(s) [2] 30124 0
2640 - Albury
Recruitment postcode(s) [3] 30125 0
3128 - Box Hill
Recruitment postcode(s) [4] 30122 0
3355 - Wendouree
Recruitment postcode(s) [5] 30130 0
5000 - Adelaide
Recruitment postcode(s) [6] 30129 0
5042 - Bedford Park
Recruitment outside Australia
Country [1] 22514 0
New Zealand
State/province [1] 22514 0
2025

Funding & Sponsors
Funding source category [1] 305534 0
Commercial sector/Industry
Name [1] 305534 0
Keros Therapeutics Australia Pty Ltd
Address [1] 305534 0
Floor 19, HWT Tower
40 City Road
Southbank, Vic, 3006
Country [1] 305534 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Keros Therapeutics Australia Pty Ltd
Address
Floor 19, HWT Tower
40 City Road
Southbank, Vic, 3006
Country
Australia
Secondary sponsor category [1] 305937 0
None
Name [1] 305937 0
Address [1] 305937 0
Country [1] 305937 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305840 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 305840 0
123 Glen Osmond Road
Eastwood, SA 5063
Ethics committee country [1] 305840 0
Australia
Date submitted for ethics approval [1] 305840 0
26/02/2020
Approval date [1] 305840 0
20/04/2020
Ethics approval number [1] 305840 0
2020-02-147

Summary
Brief summary
KER-050 is being developed by Keros Therapeutics Australia Pty Ltd as a potential treatment for anaemia in patients with very low, low or intermediate risk myelodysplastic syndromes (MDS). KER-050 is a therapeutic protein designed to increase red blood cell and platelet production by inhibiting the signaling of a subset of the TGF-ß family of proteins to promote hematopoiesis. The main purpose of this study is to test how safe the study drug is and how well the body can handle taking it (called tolerability).
The study will also look at whether the study drug works (called efficacy), the amount of the study drug in the blood (called pharmacokinetics) and how the study drug affects the body (called pharmacodynamics).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 101778 0
A/Prof David M Ross
Address 101778 0
Flinders Medical Centre
Flinders Drive, Bedford Park SA 5042
Country 101778 0
Australia
Phone 101778 0
+61 8 8204 5231
Fax 101778 0
+61 8 8204 5114
Email 101778 0
David.Ross@sa.gov.au
Contact person for public queries
Name 101779 0
Ms Rachel Barger
Address 101779 0
Keros Therapeutics
99 Hayden Avenue
Bldg. E, Suite 120
Lexington, MA 02421
Country 101779 0
United States of America
Phone 101779 0
+011 603 548 3907
Fax 101779 0
Email 101779 0
clinicalstudies@kerostx.com
Contact person for scientific queries
Name 101780 0
Dr Claudia Ordonez
Address 101780 0
Keros Therapeutics
99 Hayden Avenue
Bldg. E, Suite 120
Lexington, MA 02421
Country 101780 0
United States of America
Phone 101780 0
+011 603 548 3907
Fax 101780 0
Email 101780 0
clinicalstudies@kerostx.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual participant data will not be available. data will be analyzed by group and descriptive statistics generated.
What supporting documents are/will be available?
No other documents available
Summary results
No Results