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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05037760




Registration number
NCT05037760
Ethics application status
Date submitted
23/08/2021
Date registered
8/09/2021

Titles & IDs
Public title
Study to Evaluate KER-050 as a Monotherapy or in Combination With Ruxolitinib in Myelofibrosis
Scientific title
A Phase 2 Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of KER-050 as Monotherapy or in Combination With Ruxolitinib in Participants With Myelofibrosis
Secondary ID [1] 0 0
KER050-MF-301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myelofibrosis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - KER-050 monotherapy
Treatment: Drugs - KER-050 in combination with ruxolitinib

Experimental: Arm 1a - Dose Escalation KER-050 (SC, solution for injection, every 4 weeks) monotherapy

Experimental: Arm 1b - Dose Escalation KER-050 (SC, solution for injection, every 4 weeks) in combination with standard of care ruxolitinib (oral, tablet, twice daily)

Experimental: Arm 2a - Dose Expansion KER-050 (SC, solution for injection, every 4 weeks) monotherapy

Experimental: Arm 2b - Dose Expansion KER-050 (SC, solution for injection, every 4 weeks) in combination with standard of care ruxolitinib (oral, tablet, twice daily)

Experimental: Arm 2C (front-line monotherapy, Brazil only) - Dose Expansion KER-050 (SC, solution for injection, every 4 weeks) monotherapy


Treatment: Drugs: KER-050 monotherapy
KER-050 administered (SC) for up to 13 cycles. Participants who may have potential benefit from continued treatment, in the opinion of their investigator, may continue in the Long Term Extension after completing 13 cycles.

Treatment: Drugs: KER-050 in combination with ruxolitinib
KER-050 administered (SC) for up to 13 cycles in combination with standard of care ruxolitinib. Participants who may have potential benefit from continued treatment, in the opinion of their investigator, may continue in the Long Term Extension after completing 13 cycles.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of adverse events (Safety and Tolerability)
Timepoint [1] 0 0
52 Weeks
Secondary outcome [1] 0 0
Evaluate the effect of KER-050 on progression to AML or accelerated MF
Timepoint [1] 0 0
52 weeks
Secondary outcome [2] 0 0
Evaluate the effect of KER-050 on progression to AML or accelerated MF
Timepoint [2] 0 0
52 weeks
Secondary outcome [3] 0 0
Evaluate the effect of KER-050 on anemia
Timepoint [3] 0 0
24 weeks
Secondary outcome [4] 0 0
Evaluate the effect of KER-050 on anemia
Timepoint [4] 0 0
24 weeks
Secondary outcome [5] 0 0
Evaluate the effect of KER-050 on anemia
Timepoint [5] 0 0
24 weeks
Secondary outcome [6] 0 0
Evaluate the effect of KER-050 on anemia
Timepoint [6] 0 0
24 weeks
Secondary outcome [7] 0 0
Evaluate the effect of KER-050 on MF disease manifestations and symptoms
Timepoint [7] 0 0
52 weeks
Secondary outcome [8] 0 0
Evaluate the effect of KER-050 on MF disease manifestations and symptoms
Timepoint [8] 0 0
52 weeks
Secondary outcome [9] 0 0
Evaluate the PK profile of KER-050
Timepoint [9] 0 0
52 weeks
Secondary outcome [10] 0 0
Evaluate the PK profile of KER-050
Timepoint [10] 0 0
52 weeks
Secondary outcome [11] 0 0
Evaluate the PK profile of KER-050
Timepoint [11] 0 0
52 weeks
Secondary outcome [12] 0 0
Evaluate the PK profile of KER-050
Timepoint [12] 0 0
Through Cycle 1 (each cycle is 28 days)
Secondary outcome [13] 0 0
Evaluate the PK profile of KER-050
Timepoint [13] 0 0
52 weeks
Secondary outcome [14] 0 0
Evaluate the PK profile of KER-050
Timepoint [14] 0 0
52 weeks
Secondary outcome [15] 0 0
Evaluate the effect of KER-050 on erythropoiesis
Timepoint [15] 0 0
52 weeks
Secondary outcome [16] 0 0
Evaluate the effect of KER-050 on erythropoiesis
Timepoint [16] 0 0
52 weeks
Secondary outcome [17] 0 0
Evaluate the effect of KER-050 on erythropoiesis
Timepoint [17] 0 0
52 weeks
Secondary outcome [18] 0 0
Evaluate the effect of KER-050 on erythropoiesis
Timepoint [18] 0 0
52 weeks
Secondary outcome [19] 0 0
Evaluate the effect of KER-050 on erythropoiesis
Timepoint [19] 0 0
52 weeks

Eligibility
Key inclusion criteria
1. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information in accordance with national and local study participant privacy regulations.
2. In the opinion of the Investigator, the participant is able and willing to comply with the requirements of the protocol (e.g., all study procedures, return for follow-up visits).
3. Male or female =18 years of age, at the time of signing informed consent.
4. Eastern Cooperative Oncology Group (ECOG) performance score =2 (see Appendix 2).
5. Life expectancy =12 months per Investigator assessment.
6. Confirmed diagnosis of PMF (prefibrotic or overtly fibrotic) according to the 2016 World Health Organization (WHO) criteria (see Appendix 3), post-PV MF, or post-ET MF according to the 2008 International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria (see Appendix 4).
7. Anemia, defined as:

1. Having received =6 units of RBC transfusion for Hgb =8.5 g/dL in the 12 weeks prior to the planned C1D1, including =1 unit of RBC transfusion in the 28 days prior to C1D1; or
2. Having =3 evaluable Hgb measurements at <10.0 g/dL including =1 evaluable Hgb measurement assessed 8 to 13 weeks prior to C1D1. Participants receiving RBC transfusions but not meeting criterion "a." may enroll under criterion "b." following the below parameters:

* All pre-transfusion Hgb values (defined as a Hgb assessed within the 3 days prior to a transfusion) should be recorded, and =1 pre-transfusion Hgb value is required.
* Hgb values collected within the 28 days following a transfusion will not be considered evaluable unless qualifying as a pre-transfusion Hgb; in cases where multiple transfusions are given in succession due to poor Hgb response, only the first pre-transfusion Hgb will be considered evaluable.
8. Arm-specific criteria:

Arms 1A and 2A:
1. Previously treated with JAK inhibitor(s) and, per the Investigator, discontinued due to one of the following reasons:

* Relapsed disease following treatment with JAK inhibitor(s)
* Refractory to treatment with JAK inhibitor(s)
* Intolerance to treatment with JAK inhibitor(s)
* Participant no longer met risk/benefit ratio to continue JAK inhibitor(s) OR
* Participant with prognostic score of intermediate-1 or higher per Dynamic International Prognostic Scoring System (DIPSS; see Appendix 7) and is ineligible for JAK inhibitor(s) in the opinion of the Investigator
2. Participants previously treated with JAK inhibitor(s) must have discontinued JAK inhibitor therapy =8 weeks before C1D1

Arms 1B and 2B:
1. Has been receiving ruxolitinib prescribed for a diagnosis of PMF (prefibrotic or overtly fibrotic), post-PV MF, or post-ET MF for =8 weeks prior to C1D1 and on a stable dose for =4 weeks prior to C1D1. In Arm 2B only, at least 10 participants should have been on ruxolitinib for <6 months prior to C1D1.
2. Meets =1 of the following criteria in the opinion of the Investigator:

* Current ruxolitinib treatment is considered to be providing insufficient control of the disease
* The participant's cytopenias are limiting the participant's ruxolitinib dose intensity
* The participant's disease is symptomatic and warrants additional therapy

Arm 2C (Brazil only):
1. No prior treatment with JAK inhibitor(s) and no access to JAK inhibitor therapy as determined by the Investigator
2. Platelet count = 50 × 109/L
3. Spleen volume = 450 cm3 as assessed by CT or MRI collected during the pretreatment period
4. MF-SAF-TSS meeting at least one of the following criteria during the pretreatment period:

* 2 symptoms with average score = 3
* Average total score = 10
9. Females of childbearing potential and sexually active males must agree to use highly effective methods of contraception as described in the protocol.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Medical History:

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. Presence of the following cardiac conditions:

1. New York Heart Association Class 3 or 4 heart failure
2. QTcF (QT interval corrected by Fridericia's formula) >500 msec on the screening or C1D1 electrocardiogram (ECG; mean of 3 measurements)
3. Uncontrolled clinically significant arrhythmia (participants with rate-controlled atrial fibrillation are not excluded)
4. Acute myocardial infarction or unstable angina pectoris =6 months prior to C1D1
3. Body mass index (BMI) =40 kg/m2.
4. Presence of uncontrolled hypertension, defined as systolic blood pressure =160 mmHg or diastolic blood pressure =100 mmHg despite adequate treatment.
5. History of drug or alcohol abuse (as defined by the Investigator) within the past 2 years.
6. History of stroke, deep venous thrombosis, or arterial embolism within 6 months prior to C1D1.
7. Major surgery within 28 days prior to C1D1. Participants must have completely recovered from any previous surgery prior to C1D1 in the opinion of the Investigator.
8. Known positive for HIV, active infectious hepatitis B with positive viral load (hepatitis B virus [HBV] DNA), or active infectious hepatitis C with positive viral load (hepatitis C virus [HCV] RNA). Participants without a known positive history of HIV, HBV, and/or HCV do not require further testing, unless testing is mandated per local guidelines.
9. Any malignancy other than PMF, post-ET MF, or post-PV MF that has not been in remission and/or has required systemic therapy including radiation, chemotherapy, hormonal therapy, or biologic therapy, within 1 year prior to C1D1. In situ cancers, squamous cell and basal cell carcinomas, and monoclonal gammopathy of unclear significance are allowed at the discretion of the Investigator.
10. History of solid organ or hematological transplantation.
11. History of severe allergic or anaphylactic reaction(s) or hypersensitivity to recombinant proteins or excipients in the investigational drug, or ruxolitinib for participants enrolling in Arm 1B or 2B.
12. Diagnosis of hemolytic anemia, active bleeding, hemoglobinopathies, or congenital disorders as a cause of the participant's anemia.
13. History of intracranial hemorrhage (any grade).
14. NCI CTCAE Grade =2 bleeding events within the 3 months prior to C1D1.
15. Receipt of an RBC or platelet transfusion for any reason(s) or combination of reasons other than underlying MF within the 12 weeks prior to C1D1. If a participant requires a transfusion for an unanticipated reason during the Pretreatment Period, a prolonged screening period may be considered after discussion with the Medical Monitor.

Treatment History:
16. Prior treatment with luspatercept, sotatercept, or other commercially available or investigational TGF-ß inhibitors (all arms).
17. Treatment within 28 days prior to C1D1 with:

1. ESA
2. Granulocyte colony-stimulating factor (G-CSF)
3. Granulocyte-macrophage colony-stimulating factor (GM-CSF)
4. TPO agonists
5. IMiDs (e.g., thalidomide, pomalidomide, lenalidomide)
6. Interferon
7. Hydroxyurea
8. Steroids at doses exceeding corticosteroid equivalent of 10 mg/day prednisone
18. Newly initiated iron chelation therapy within the 8 weeks prior to C1D1. Stable doses of iron chelators are allowed if prescribed per label.
19. Vitamin B12 and/or folate therapy initiated within 28 days prior to C1D1. Participants on stable replacement doses for =8 weeks and without concurrent vitamin B12 or folate deficiency are allowed.
20. Treatment with another investigational drug or device or approved therapy for the treatment of MF or anemia in MF =28 days 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.
21. For Arms 1B and 2B (participants receiving ruxolitinib), initiation of treatment with strong cytochrome P450 (CYP)3A4 inhibitors within 2 weeks prior to C1D1. Participants receiving CYP3A4 inhibitors/inducers as concomitant therapy with ruxolitinib in accordance with ruxolitinib local prescribing information may continue to receive such therapies in this study.

Laboratory Exclusions (during screening):
22. Bone marrow aspirate blast percentage >5%

a. In the event of a non-evaluable pretreatment bone marrow aspirate expected to be due to marrow fibrosis, participants may be enrolled without bone marrow aspirate blast percentage data if all other eligibility criteria are met. Historical bone marrow data may be requested to support confirmation of diagnosis.
23. Peripheral blood blast percentage =10%
24. Platelet count <25 × 109/L or >450 × 109/L
25. Persistent Hgb <7 g/dL despite RBC transfusions
26. Transferrin saturation <15%
27. Ferritin <50 ng/mL
28. Folate <4.5 nmol/L (<2.0 pg/L)
29. Vitamin B12 <148 pmol/L (<200 pg/mL)
30. Estimated glomerular filtration rate <40 mL/min/1.73 m2 (as determined by the Chronic Kidney Disease Epidemiology Collaboration equation)
31. AST or ALT >2.5 × ULN
32. Total bilirubin >1.5 × ULN
33. INR >1.2 × ULN, unless participant is receiving anticoagulation, in which instance the INR must fall within the participant's designated therapeutic range.

Miscellaneous:
34. Pregnant or lactating females.
35. Any other condition not specifically noted above that, in the opinion of the Investigator or Sponsor, would preclude the participant from participating in the study.
36. Participants who are investigational site staff members directly involved in the conduct of the study and their immediate family members, site staff members otherwise supervised by the Investigator, or participants who are Keros or contract research organization (CRO) employees directly involved in the conduct of the study. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.

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)
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
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
16/12/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/01/2029
Actual
Sample size
Target
120
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Concord Hospital - Concord
Recruitment hospital [2] 0 0
The Tweed Hospital - Tweed Heads
Recruitment hospital [3] 0 0
Flinders Medical Centre - Woodville South
Recruitment hospital [4] 0 0
St. Vincent's Hospital Melbourne - Fitzroy
Recruitment hospital [5] 0 0
Royal Melbourne Hospital - Melbourne
Recruitment hospital [6] 0 0
Ballarat Oncology & Hematology Service - Wendouree
Recruitment postcode(s) [1] 0 0
- Concord
Recruitment postcode(s) [2] 0 0
2485 - Tweed Heads
Recruitment postcode(s) [3] 0 0
5042 - Woodville South
Recruitment postcode(s) [4] 0 0
3355 - Fitzroy
Recruitment postcode(s) [5] 0 0
3050 - Melbourne
Recruitment postcode(s) [6] 0 0
3355 - Wendouree
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Washington
Country [2] 0 0
Brazil
State/province [2] 0 0
Porto Alegre
Country [3] 0 0
Brazil
State/province [3] 0 0
São Paulo
Country [4] 0 0
France
State/province [4] 0 0
Amiens
Country [5] 0 0
France
State/province [5] 0 0
Brest
Country [6] 0 0
France
State/province [6] 0 0
Cesson-Sévigné
Country [7] 0 0
France
State/province [7] 0 0
Lyon
Country [8] 0 0
France
State/province [8] 0 0
Nîmes
Country [9] 0 0
France
State/province [9] 0 0
Orléans
Country [10] 0 0
Italy
State/province [10] 0 0
Bari
Country [11] 0 0
Italy
State/province [11] 0 0
Bologna
Country [12] 0 0
Italy
State/province [12] 0 0
Brescia
Country [13] 0 0
Italy
State/province [13] 0 0
Firenze
Country [14] 0 0
Italy
State/province [14] 0 0
Genova
Country [15] 0 0
Italy
State/province [15] 0 0
Milano
Country [16] 0 0
Italy
State/province [16] 0 0
Reggio Emilia
Country [17] 0 0
Italy
State/province [17] 0 0
Roma
Country [18] 0 0
Italy
State/province [18] 0 0
Varese
Country [19] 0 0
Italy
State/province [19] 0 0
Verona
Country [20] 0 0
Korea, Republic of
State/province [20] 0 0
Incheon
Country [21] 0 0
Korea, Republic of
State/province [21] 0 0
Seoul
Country [22] 0 0
Spain
State/province [22] 0 0
Barcelona
Country [23] 0 0
Spain
State/province [23] 0 0
Madrid
Country [24] 0 0
Spain
State/province [24] 0 0
Salamanca
Country [25] 0 0
Spain
State/province [25] 0 0
Valencia
Country [26] 0 0
Spain
State/province [26] 0 0
Zaragoza
Country [27] 0 0
United Kingdom
State/province [27] 0 0
Boston
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Leeds
Country [29] 0 0
United Kingdom
State/province [29] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Keros Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Clinical Study Team
Address 0 0
Country 0 0
Phone 0 0
(617) 314-6297
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05037760