Mieloma Múltiple

Principales Criterios de Inclusión:

• Subject is ≥18 years of age at the time of signing the ICF.
• Subject has a diagnosis of PMF according to the 2016 World Health Organization (WHO) criteria or diagnosis of post-ET or post-PV MF according to the IWG-MRT 2007 criteria , confirmed by the most recent local pathology report.
• Subject is requiring RBC transfusions as defined as:
  – a. Average RBC-transfusion frequency: 4 to 12 RBC units/12 weeks immediately up to randomization. There must be no interval > 6 weeks (42 days) without ≥ 1 RBC transfusion.
  – b. RBC transfusions are scored in determining eligibility when given for treatment of:
• Symptomatic (ie, fatigue or shortness of breath) anemia with a pretransfusion Hgb ≤ 9.5 g/dL or Asymptomatic anemia with a pretransfusion Hgb ≤ 7 g/dL c. RBC transfusions given for worsening of anemia due to bleeding or infections are not scored in determining eligibility.
• Subjects on continuous (eg, absent of dose interruptions lasting ≥ 2 consecutive weeks) JAK2 inhibitor therapy as approved in the country of the study site for the treatment for MPN-associated MF as part of their standard-of-care therapy for at least 32 weeks, on stable daily dose for at least 16 weeks immediately up to the date of randomization and anticipated to be on a stable daily dose of that JAK2 inhibitor for at least 24 weeks after randomization.
• Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2.
• A female of childbearing potential (FCBP) for this study is defined as a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (eg, has had menses at any time in the preceding 24 consecutive months). Females of childbearing potential (FCBP)participating in the study must:
  – a. Have 2 negative pregnancy tests as verified by the Investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the study, and after end of IP. This applies even if the subject practices true abstinence* from heterosexual contact.
  – b. Either commit to true abstinence* from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with, effective contraception** without interruption, 28 days prior to starting IP, during the study therapy (including dose interruptions), and for 12 weeks (approximately 5 times the mean terminal half-life of IP based on multiple-dose PK data) after discontinuation of study therapy.
• Male subjects must: Practice true abstinence* (which must be reviewed on a monthly basis) or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential** while participating in the study, during dose interruptions and for at least 12 weeks (approximately 5 times the mean terminal half-life of IP based on multiple-dose PK data) following IP discontinuation, even if he has undergone a successful vasectomy.

* True abstinence is acceptable when it is in line with the preferred and usual lifestyle of the subject. [Periodic abstinence (eg, calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception.]

** Agreement to use highly effective methods of contraception that alone or in combination result in a failure rate of a Pearl index of less than 1% per year when used consistently and correctly throughout the course of the study. Such methods include: Combined (estrogen and progestogen containing) hormonal contraception: Oral, Intravaginal, Transdermal; Progestogen-only hormonal contraception associated with inhibition of ovulation: Oral, Injectable hormonal contraception, Implantable hormonal contraception; Placement of an intrauterine device (IUD); Placement of an intrauterine hormone-releasing system (IUS); Bilateral tubal occlusion; Vasectomized partner; Sexual Abstinence.

• Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
• Subject is willing and able to adhere to the study visit schedule and other protocol requirements including the use of the electronic patient reported outcomes device.