COntrolled MyeloFibrosis Study With ORal JAK Inhibitor Treatment: The COMFORT-I Trial

Patients with spleen growth of greater than 25% based on an increase in spleen volume from
Baseline were eligible for early unblinding, and for patients on placebo, cross over to
ruxolitinib prior to the primary study endpoint being reached. If this spleen growth occurred
before Week 24, it must have been accompanied by specific worsening of symptoms, based on
worsening early satiety accompanied by weight loss or worsening pain requiring daily narcotic
use. After Week 24, asymptomatic spleen growth alone was sufficient for early unblinding and
potential cross over. Patients found to have been randomized to ruxolitinib after early
unblinding prior to Week 24 were discontinued.

When half of the patients remaining in the study completed the Week 36 visit and all patients
enrolled completed Week 24 or discontinued, the database was frozen and the primary analysis
was conducted. Once this was complete, all patients were unblinded and patients who had been
randomized to placebo were given the opportunity to cross over to ruxolitinib treatment,
provided hematology laboratory parameters were adequate; Patients receiving benefit could
continue treatment until the later of marketing approval or when the last randomized patient
remaining in the study had completed Week 144 (36 months).

Inclusion Criteria:

- Subjects must be diagnosed with primary myelofibrosis (PMF), post-polycythemia
vera-myelofibrosis (PPV-MF) or post-essential thrombocythemia-myelofibrosis (PET-MF)
according to the 2008 World Health Organization criteria

- Subjects with myelofibrosis requiring therapy must be classified as high risk OR
intermediate risk level 2 according to the prognostic factors defined by the
International Working Group

- Subjects with an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1,
2 or 3

- Subjects who have not previously received treatment with a Janus kinase (JAK)
inhibitor

Exclusion Criteria:

- Subjects with a life expectancy of less than 6 months

- Subjects with inadequate bone marrow reserve as demonstrated by specific clinical
laboratory counts

- Subjects with inadequate liver or renal function

- Subjects with clinically significant bacterial, fungal, parasitic or viral infection
which require therapy

- Subjects with an active malignancy over the previous 5 years except specific skin
cancers.

- Subjects with severe cardiac conditions

- Subjects who have had splenic irradiation within 12 months