Exploratory Phase II Study of INC424 Patients With Primary Myelofibrosis (PMF) or Post Polycythaemia Myelofibrosis (PPV MF) or Post Essential Thrombocythaemia Myelofibrosis (PET-MF)

Treatment success was defined as a 50% or greater reduction in palpable spleen length versus baseline at 48 weeks and/or a 50% or greater improvement in total symptom score (derived from the MF symptom assessment form (MFSAF) questionnaire) versus baseline at the week 48 time point. The MFSAF assesses the following symptoms (all scored from absent (0) to worst imaginable (10)): general fatigue, abdominal pain (and discomfort), inactivity (ability to move and walk around), cough, night sweats, itching (pruritus), bone pain (diffuse not joint pain or arthritis), fever, change in appetite/unintentional weight loss (or gain) in past 6 months, overall quality of life (QoL).

Time frame: 48 Weeks

Population: Full analysis set (FAS): The FAS included all participants who received at least one administration of study drug and had at least one post-baseline efficacy assessment.

The EQ-5D is a standardized instrument used for measuring health outcomes in a wide range of health conditions and treatment. It consists of a descriptive system and a visual analogue scale (EQ-VAS). The descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. The EQ-VAS records the participant's self-rated health on a vertical, VAS where the endpoints are labeled 'best imaginable health state' and 'worst imaginable health state'. The EQ-5D health state was converted to a single summary index by applying a formula that attaches a weight to each of the levels in each dimension. The final EQ5D preference index scores range from 0 to 1 with higher scores indicating better health.

Time frame: Baseline, week 4, week 12, week 24, week 48

Population: Only participants from the full analysis set (FAS), who had evaluable measurements at both baseline and the post-baseline week time point, was included in the analysis for that time point. The FAS included all participants who received at least one administration of study drug and had at least one post-baseline efficacy assessment.

The MF-SAF consists of seven questions about key symptoms and impact of MF. Questions are scored on a scale of 0-10, with higher scores indicating more severe symptoms and greater inactivity. Questions 1-6, which together comprise a Total Symptom Score (TSS), investigate the following symptoms: night sweats, pruritus/itching, abdominal discomfort, pain under the ribs, early satiety and bone/muscle pain. Question 7 asks patients to report levels of inactivity. The TSS reflects the sum of the scores of these symptoms excluding inactivity, with the maximum possible score being 60 (most severe symptom experienced).

Time frame: Baseline, week 4, week 12, week 24, week 48

Population: Only participants from the full analysis set (FAS), who had evaluable measurements at both baseline and the post-baseline week time point, was included in the analysis for that time point. The FAS included all participants who received at least one administration of study drug and had at least one post-baseline efficacy assessment.

MRU was assessed according to the mean duration of hospitalization visits.

Time frame: week 48

Population: Participants from the full analysis set, who were hospitalized between baseline and week 48, were included in the analysis.

MRU was assessed according to the number of accidents and emergency room visits.

Time frame: baseline to week 12, week 12 to week 24, week 24 to week 36, week 36 to week 48

Population: Only participants from the full analysis set (FAS), who had evaluable measurements at each timeframe, e.g. from baseline to week 12, were included in the analysis for that timeframe. The FAS included all participants who received at least one administration of study drug and had at least one post-baseline efficacy assessment.

MRU was assessed according to the number of GP, specialists', and urgent care visits.

Time frame: baseline to week 12, week 12 to, week 24, week 24 to week 36, week 36 to week 48

Population: Only participants from the full analysis set (FAS), who had evaluable measurements at each timeframe, e.g. from baseline to week 12, were included in the analysis for that timeframe. The FAS included all participants who received at least one administration of study drug and had at least one post-baseline efficacy assessment.

Medical resource utilization (MRU) was assessed according to the number of hospitalizations.

Time frame: week 12, week 24, week 26, week 48

Population: Only participants from the full analysis set (FAS), who had evaluable measurements at the post-baseline week time point, were included in the analysis for that time point. The FAS included all participants who received at least one administration of study drug and had at least one post-baseline efficacy assessment.

Response to treatment and disease progression was assessed by physical examination, specifically assessing changes in spleen size by palpation. Disease response and progression was evaluated using the International Working Group for myelofibrosis Research and Treatment Response Criteria.

Time frame: week 48

Population: Full Analysis Set (FAS): The FAS included all participants who received at least one administration of study drug and had at least one post-baseline efficacy assessment.

Transfusion dependency status from baseline through the end of study was assessed. New onset of transfusion dependency was defined as the use of 2 or more units of red blood cell products during the 8 weeks prior to a study visit. New onset of transfusion independency was defined as the use of 0 or 1 unit of red blood cell products during the 8 weeks prior to a study visit.

Time frame: baseline (BL), end of treatment (up to 28 days post last treatment) (EOT)

Population: Full analysis set (FAS): The FAS included all participants who received at least one administration of study drug and had at least one post-baseline efficacy assessment.