Clinical Trials Register

Summary
EudraCT Number:	2021-001838-19
Sponsor's Protocol Code Number:	KER050-MD-201
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-11-02
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Czechia - SUKL

A.2

EudraCT number

2021-001838-19

A.3

Full title of the trial

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)

Otevřené klinické hodnocení fáze 2 se vzestupnou dávkou přípravku KER-
050 k léčbě anémie u pacientů s myelodysplastickým syndromem (MDS) s
velmi nízkým, nízkým nebo středním rizikem.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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)

A.4.1

Sponsor's protocol code number

KER050-MD-201

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Keros Therapeutics, Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Keros Therapeutics, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Keros Therapeutics, Inc.
B.5.2	Functional name of contact point	Central Contact Person
B.5.3	Address:
B.5.3.1	Street Address	1050 Waltham Street, Suite 302
B.5.3.2	Town/ city	Lexington
B.5.3.3	Post code	02421
B.5.3.4	Country	United States
B.5.6	E-mail	ker050-md-201@kerostx.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	KER-050
D.3.2	Product code	PRD8997233
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PRD8997233
D.3.9.1	CAS number	2727114-26-1
D.3.9.2	Current sponsor code	KER-050
D.3.9.3	Other descriptive name	KER-050
D.3.9.4	EV Substance Code	SUB224243
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	68 - 82
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Anemia in Patients with Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MDS).

E.1.1.1

Medical condition in easily understood language

Myelodysplastic syndromes (MDS) are conditions that are observed when the blood-forming cells in the bone marrow become abnormal.

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10028533
E.1.2	Term	Myelodysplastic syndrome
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10002272
E.1.2	Term	Anemia
E.1.2	System Organ Class	100000004851

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

Part 1: Dose Escalation
• To evaluate the safety and tolerability of ascending doses of KER-050 in participants with very low, low, or intermediate risk MDS in order to determine the dose(s) that will be evaluated in Part 2 of the study.
Part 2: Dose Confirmation
• To confirm the safety and tolerability of the dose(s) selected in Part 1.
Long-Term Extension
• To evaluate the long-term safety and tolerability of KER-050 in participants with very low, low, or intermediate risk MDS.

E.2.2

Secondary objectives of the trial

Secondary Objectives (All Parts)
• To evaluate the progression to higher risk MDS or acute myeloid leukemia (AML).
• To evaluate the PD effects of KER-050 on erythropoiesis in participants with very low, low, or intermediate risk MDS, separately for ring sideroblast (RS) positive and non-RS populations.
• To evaluate the efficacy of KER-050 on anemia in participants with very low, low or intermediate risk MDS, separately for RS positive and non-RS populations.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. 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.
2. < 5% blasts in bone marrow during the Pretreatment Period.
3. Peripheral blood white blood cell (WBC) count < 13,000/µL during the Pretreatment Period.
4. Anemia defined as:
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
b. In HTB participants (defined as requiring > or = 4 units of RBCs for hemoglobin < or = 9.0 g/dL within 8 weeks)
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (if related to anemia).
6. Females of child-bearing potential and sexually active males must agree to use effective methods of contraception.

E.4

Principal exclusion criteria

1. 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.
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 with ESA within 56 days prior to C5D1.
6. Prior or concurrent chronic treatment with G-CSF or GM-CSF.
7. Iron chelation therapy if initiated within 8 weeks prior to Cycle 1 Day 1.
8. Vitamin B12 therapy within 8 weeks prior to Cycle 1 Day 1.
9. 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.
10. Platelet count > 450 x 10*9/L or < 30 x 10*9/L.
11. Transferrin saturation < 15%.
12. Ferritin < 50 µg/L.
13. Folate < 4.5 nmol/L (< 2.0 ng/mL).
14. Vitamin B12 < 148 pmol/L (< 200 pg/mL).
15. Estimated glomerular filtration rate (GFR) < 40 mL/min/1.73 m2 (as determined by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI].
16. Pregnant or lactating females.

E.5 End points

E.5.1

Primary end point(s)

Part 1 and Part 2:
Safety and tolerability (the primary endpoint) is evaluated from assessments taken at every visit (Safety and tolerability as determined by the incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs).
Long-Term Extension:
Safety and tolerability as determined by the incidence of TEAEs and SAEs over time

E.5.1.1

Timepoint(s) of evaluation of this end point

105 Weeks unless participants elect to continue in the Long-term Extension (LTE)

E.5.2

Secondary end point(s)

1. Incidence of progression to higher risk MDS or AML per World Health Organization (WHO) 2016 criteria.
2. 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.
3. Proportion of participants who achieve modified 2006 International Working Group (IWG) Hematologic Improvement-Erythroid (HI E) response overall and by RS status, where:
- In LTB participants and participants with non-transfused anemia, response is defined as a mean hemoglobin (Hgb) increase of ≥ 1.5 g/dL from Baseline during any 8 week period during the treatment period.
- In HTB participants, response is defined as a reduction by ≥ 4 units of RBCs transfused during any 8-week period on study compared with the 8-week period prior to study Cycle 1 Day 1 (C1D1).
4. 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.
5. Proportion of participants who achieve erythropoietic improvement overall and by RS status, where:
- In low-transfusion burden (LTB) participants and participants with non-transfused anemia, improvement is defined as a mean hemoglobin (Hgb) increase of ≥ 1.5 g/dL from Baseline for ≥ 14 days (in the absence of red blood cell [RBC] transfusions).
- In high transfusion burden (HTB) participants, improvement is defined as a reduction of ≥ 50% or ≥ 4 RBC units transfused compared to pretreatment over an 8-week period.
6. Mean change from baseline in hemoglobin [Time Frame: Measured over the course of study, up to approximately 25 weeks from study day 1 unless participants elect to continue on in the LTE].
7. Time to HI-E response [Time Frame: From treatment initiation to End of Study visit (approximately 25 weeks unless participants elect to continue on in the LTE)].
8. Duration of HI-E response [Time Frame: From treatment initiation to End of Study visit (approximately 25 weeks unless participants elect to continue on in the LTE)].
9. Time to TI response.
10. Duration of TI response.
11. Proportion of LTB and HTB participants who achieve TI ≥ 12 weeks, 16 weeks, 24 weeks, 48 weeks.
12. Change from baseline of red cell parameters, including reticulocyte count, mean corpuscular volume, mean corpuscular hemoglobin, and reticulocyte count, mean corpuscular volume, mean corpuscular volume, mean corpuscular hemoglobin and reticulocyte cell Hgb by visit. [Time Frame: From treatment initiation to End of Study visit (approximately 25 weeks unless participants elect to continue on in the LTE)].

E.5.2.1

Timepoint(s) of evaluation of this end point

Timepoints indicated above.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Tolerability

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

2-part Ascending Dose and Long-term Extension

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Israel

New Zealand

United States

Czechia

France

Germany

Spain

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The end of the study (EOS) for a participant is the time that they complete their final Safety Follow-up Visit and associated assessments after the EOT Visit. Participants who discontinue study treatment prematurely may complete the EOT Visit and enter the Safety Follow-up Period followed by the Survival Follow-up Period at the time of discontinuation.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

140

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Patients will continue with standard of care after trial participation ends.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2022-03-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-11-03

P. End of Trial
P.	End of Trial Status	Ongoing

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials