A Phase 2 Study to Evaluate the Efficacy and Safety of GS-6624 in Adults With Myelofibrosis

This is a Phase 2, prospective, open-label study to determine the efficacy and safety of AB0024 in subjects with Primary myelofibrosis (PMF) and Post Polycythemia Vera or Post Essential Thrombocythemia Myelofibrosis (ET/PV MF).

The study is designed as a two stage trial. In the stage 1, patients will be randomized into two cohorts to receive either 200 or 700 mg of study drug.

In the stage 2, patients on ruxolitinib will be randomized to receive either 200 or 700 mg of study drug.

• Drug: GS-6624 at 700 mg
  700 mg of GS-6624
  Other Name: Ruxolitinib
• Drug: GS-6624 at 200 mg
  GS-6624 at 200 mg
  Other Name: Ruxolitinib

• Experimental: GS-6624 - 200 mg
  Intervention: Drug: GS-6624 at 200 mg
• Experimental: GS-6624 - 700 mg
  Intervention: Drug: GS-6624 at 700 mg

Inclusion Criteria:

• Must be diagnosed with PMF or post ET/PV MF with intermediate-1, intermediate-2 or high risk disease according to the IWG prognostic scoring system, or if with low risk disease then with symptomatic splenomegaly that is ≥ 10 cm below left costal margin by physical exam.
• Must have adequate organ function as demonstrated by the following:
• ALT (SGPT) and/or AST (SGOT) ≤ 2.5x upper limit of normal (ULN), or ≤ 4x ULN (if upon judgment of the treating physician, it is believed to be due to extramedullary hematopoiesis [EMH] related to MF);
• Direct bilirubin ≤ 1.5 x ULN; or ≤ 2x ULN (if upon judgment of the treating physician, it is believed to be due to extramedullary hematopoiesis [EMH] related to MF);
• Serum creatinine ≤ 2.5 mg/dL. 2.5 mg/dL.
• In Stage 2, subjects must be on ruxolitinib for at least 8 weeks and on a stable dose for at least 4 weeks.
• ECOG performance status (PS) ≤ 2
• Treatment-related toxicities from prior therapies must have resolved to Grade ≤ 1
• Women of childbearing potential and men must agree to using one medically approved (ie, mechanical or pharmacological) contraceptive measure and have their partners agree to an additional barrier method of contraception for the duration of the study and for 90 days after the last administration of study drug. Please refer to Section 11 for a definition of female of child bearing potential and a list of acceptable contraceptive methods for this study.

Exclusion Criteria:

• Any serious medical condition or psychiatric illness that would prevent, (as judged by the treating physician) the subject from signing the informed consent form or any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
• Pregnant or lactating.
• Known history of human immunodeficiency virus (HIV), hepatitis C, or hepatitis B.
• History or presence of any form of cancer within the 3 years prior to enrollment, with the exception of excised basal cell or squamous cell carcinoma of the skin, or cervical carcinoma in situ or breast carcinoma in situ that has been excised or resected completely and is without evidence of local recurrence or metastasis.
• Participation in an investigational drug or device trial within 2 weeks prior to study Day 1 or within 5 times the half-life of the investigational agent in the other clinical study, if known.
• Use of any cytotoxic chemotherapeutic agents (eg, hydroxyurea), corticosteroids (prednisone ≤ 10 mg/day or corticosteroid equivalent is allowed), or immunodulators (eg, thalidomide) within 2 weeks and interferon use within 4 weeks prior to study Day 1.
• Symptomatic congestive heart failure (New York Heart Association Classification > Class II), unstable angina, or unstable cardiac arrhythmia requiring medication.
• History of surgery within 2 weeks prior to enrollment or anticipated surgery during the study period.
• Any other condition that might reduce the chance of obtaining data required by the protocol or that might compromise the ability to give truly informed consent.