The primary objective of this study is to evaluate the efficacy of INC424 in patients with PMF, PPV MF, or PET-MF using a composite measure of either an objective endpoint (\> 50% reduction in splenomegaly using palpitation at 48 weeks) and/or a subjective endpoint (\>50% reduction in total symptom score at 48 weeks).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
48
Ruxolitinib was provided in 5 mg tablets, packaged in bottles. 15 - 20 mg (dose based on Baseline platelet count) twice daily.
Novartis Investigative Site
Cardiff, Wales, United Kingdom
Novartis Investigative Site
Bournemouth, United Kingdom
Novartis Investigative Site
East Yorkshire, United Kingdom
Novartis Investigative Site
Edinburgh, United Kingdom
Novartis Investigative Site
Leicester, United Kingdom
Novartis Investigative Site
Liverpool, United Kingdom
Novartis Investigative Site
London, United Kingdom
Novartis Investigative Site
London, United Kingdom
Novartis Investigative Site
Manchester, United Kingdom
Novartis Investigative Site
Oxford, United Kingdom
Percentage of Participants With Treatment Success
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
Percentage of Participants With Best Overall Response
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
Change From Baseline in Myelofibrosis Symptoms Assessment Form (MF-SAF)
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
Change From Baseline in EQ5D Preference Index (5 Level EuroQol Questionnaire Determining Quality of Life) From Baseline
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
Number of Hospitalizations
Medical resource utilization (MRU) was assessed according to the number of hospitalizations.
Time frame: week 12, week 24, week 26, week 48
Duration of Hospitalizations
MRU was assessed according to the mean duration of hospitalization visits.
Time frame: week 48
Number of Accident & Emergency Visits From Baseline
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
Number of General Practitioner (GP), Specialists' and Urgent Care Visits
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
Percentage of Participants With Transfusion Dependency Status
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)
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