Efficacy and Safety of Simtuzumab in Adults With Primary, Post Polycythemia Vera or Post Essential Thrombocythemia Myelofibrosis

Inclusion Criteria:

   - Must be diagnosed with PMF or post ET/PV MF with intermediate-1, intermediate-2 or
   high risk disease according to the international working group (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:

   - Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤ 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.

   - In Stage 2, participants must be on ruxolitinib for at least 8 weeks and on a stable
   dose for at least 4 weeks.

   - Eastern cooperative oncology group (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. Definition of female of
   child bearing potential and a list of acceptable contraceptive methods for this study
   applies per protocol.

Exclusion Criteria:

   - Any serious medical condition or psychiatric illness that would prevent, (as judged by
   the treating physician) the participant from signing the informed consent form or any
   condition, including the presence of laboratory abnormalities, which places the
   participant 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 immune modulators
   (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.