A Study of Elritercept Alone or Together With Ruxolitinib in Adults With Myelofibrosis

Exclusion Criteria53

• Medical History:
• 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.
• Presence of the following cardiac conditions:
• New York Heart Association Class 3 or 4 heart failure
• QTcF (QT interval corrected by Fridericia's formula) >500 milliseconds (msec) on the screening or C1D1 electrocardiogram (ECG; mean of 3 measurements)
• Uncontrolled clinically significant arrhythmia (participants with rate-controlled atrial fibrillation are not excluded)
• Acute myocardial infarction or unstable angina pectoris ≤6 months prior to C1D1
• Body mass index (BMI) ≥40 kilograms per meter square (kg/m\^2).
• Presence of uncontrolled hypertension, defined as systolic blood pressure ≥160 millimeters of mercury (mmHg) or diastolic blood pressure ≥100 mmHg despite adequate treatment.
• History of drug or alcohol abuse (as defined by the Investigator) within the past 2 years.
• History of stroke, deep venous thrombosis, or arterial embolism within 6 months prior to C1D1.
• 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.
• Known positive for human immunodeficiency virus (HIV), active infectious hepatitis B with positive viral load (hepatitis B virus \[HBV\] deoxyribonucleic acid \[DNA\]), or active infectious hepatitis C with positive viral load (hepatitis C virus \[HCV\] ribonucleic acid \[RNA\]). Participants without a known positive history of HIV, HBV, and/or HCV do not require further testing, unless testing is mandated per local guidelines.
• 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.
• History of solid organ or hematological transplantation.
• 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.
• Diagnosis of hemolytic anemia, active bleeding, hemoglobinopathies, or congenital disorders as a cause of the participant's anemia.
• History of intracranial hemorrhage (any grade).
• National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2 bleeding events within the 3 months prior to C1D1.
• 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:
• Prior treatment with luspatercept, sotatercept, or other commercially available or investigational transforming growth factor-beta (TGF-β) inhibitors (all arms).
• Treatment within 28 days prior to C1D1 with:
• Erythropoiesis-stimulating agent (ESA)
• Granulocyte colony-stimulating factor (G-CSF)
• Granulocyte-macrophage colony-stimulating factor (GM-CSF)
• Thrombopoietin (TPO) agonists
• Immunomodulator imide drugs (IMiDs) (e.g., thalidomide, pomalidomide, lenalidomide)
• Interferon
• Hydroxyurea
• Steroids at doses exceeding corticosteroid equivalent of 10 mg/day prednisone
• Newly initiated iron chelation therapy within the 8 weeks prior to C1D1. Stable doses of iron chelators are allowed if prescribed per label.
• Vitamin B12 and/or folate therapy initiated within 4 weeks before randomization. Participants on stable replacement doses for ≥4 weeks and without concurrent vitamin B12 or folate deficiency are allowed.
• 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.
• 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):
• Bone marrow aspirate blast percentage >5 percent (%)
• 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.
• Peripheral blood blast percentage ≥10%
• Platelet count <25 × 10\^9 per liter (10\^9/)L or >450 × 10\^9/L
• Persistent Hgb <7 g/dL despite RBC transfusions
• Transferrin saturation <15%
• Ferritin <50 nanograms per mililiters (ng/mL)
• Folate <4.5 nanomoles per liter (nmol/L) (<2.0 picograms per liter (pg/L))
• Vitamin B12 <148 picomoles per liter (pmol/L) (<200 picograms per milliliter (pg/mL))
• Estimated glomerular filtration rate <30 milliliters per minute per 1.73 square meter (mL/min/1.73 m\^2) (as determined by the Chronic Kidney Disease Epidemiology Collaboration equation)
• Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) >3 × upper limit of normal (ULN)
• Total bilirubin >2 × ULN
• International normalized ratio (INR) >1.2 × ULN, unless participant is receiving anticoagulation, in which instance the INR must fall within the participant's designated therapeutic range.
• Miscellaneous:
• Pregnant or lactating females.
• 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.
• 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.