Trial Outcomes & Findings for Exploratory Phase II Study of INC424 Patients With Primary Myelofibrosis (PMF) or Post Polycythaemia Myelofibrosis (PPV MF) or Post Essential Thrombocythaemia Myelofibrosis (PET-MF) (NCT NCT01558739)
NCT ID: NCT01558739
Last Updated: 2015-03-03
Results Overview
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).
COMPLETED
PHASE4
48 participants
48 Weeks
2015-03-03
Participant Flow
54 patients were screened. 48 patients were enrolled as planned.
Participant milestones
| Measure |
INC424
Patients diagnosed with PMF, PPV MF, or PET-MF were treated with oral INC424 at a dose of 15 - 20 mg (dose based on Baseline platelet count) twice daily.
|
|---|---|
|
Overall Study
STARTED
|
48
|
|
Overall Study
COMPLETED
|
31
|
|
Overall Study
NOT COMPLETED
|
17
|
Reasons for withdrawal
| Measure |
INC424
Patients diagnosed with PMF, PPV MF, or PET-MF were treated with oral INC424 at a dose of 15 - 20 mg (dose based on Baseline platelet count) twice daily.
|
|---|---|
|
Overall Study
Adverse Event
|
7
|
|
Overall Study
Withdrawal by Subject
|
2
|
|
Overall Study
Death
|
3
|
|
Overall Study
Disease Progression
|
4
|
|
Overall Study
Protocol Violation
|
1
|
Baseline Characteristics
Exploratory Phase II Study of INC424 Patients With Primary Myelofibrosis (PMF) or Post Polycythaemia Myelofibrosis (PPV MF) or Post Essential Thrombocythaemia Myelofibrosis (PET-MF)
Baseline characteristics by cohort
| Measure |
INC424
n=48 Participants
Patients diagnosed with PMF, PPV MF, or PET-MF were treated with oral INC424 at a dose of 15 - 20 mg (dose based on Baseline platelet count) twice daily.
|
|---|---|
|
Age, Continuous
|
69.12 Years
STANDARD_DEVIATION 10.419 • n=5 Participants
|
|
Sex: Female, Male
Female
|
21 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
27 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 48 WeeksPopulation: 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.
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).
Outcome measures
| Measure |
INC424
n=48 Participants
Patients diagnosed with PMF, PPV MF, or PET-MF were treated with oral INC424 at a dose of 15 - 20 mg (dose based on Baseline platelet count) twice daily.
|
|---|---|
|
Percentage of Participants With Treatment Success
|
50 Percentage of participants
|
SECONDARY outcome
Timeframe: week 48Population: 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.
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.
Outcome measures
| Measure |
INC424
n=48 Participants
Patients diagnosed with PMF, PPV MF, or PET-MF were treated with oral INC424 at a dose of 15 - 20 mg (dose based on Baseline platelet count) twice daily.
|
|---|---|
|
Percentage of Participants With Best Overall Response
Clinical improvement
|
6.3 Percentage of participants
|
|
Percentage of Participants With Best Overall Response
Complete response
|
6.3 Percentage of participants
|
|
Percentage of Participants With Best Overall Response
Partial response
|
39.6 Percentage of participants
|
|
Percentage of Participants With Best Overall Response
Stable disease
|
47.9 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, week 4, week 12, week 24, week 48Population: 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).
Outcome measures
| Measure |
INC424
n=48 Participants
Patients diagnosed with PMF, PPV MF, or PET-MF were treated with oral INC424 at a dose of 15 - 20 mg (dose based on Baseline platelet count) twice daily.
|
|---|---|
|
Change From Baseline in Myelofibrosis Symptoms Assessment Form (MF-SAF)
Week 4 (n=37)
|
-8.78 score on a scale
Standard Deviation 10.638
|
|
Change From Baseline in Myelofibrosis Symptoms Assessment Form (MF-SAF)
Week 12 (n=35)
|
-8.46 score on a scale
Standard Deviation 12.871
|
|
Change From Baseline in Myelofibrosis Symptoms Assessment Form (MF-SAF)
Week 24 (n=30)
|
-9.13 score on a scale
Standard Deviation 11.950
|
|
Change From Baseline in Myelofibrosis Symptoms Assessment Form (MF-SAF)
Week 48 (n=18)
|
-7.83 score on a scale
Standard Deviation 9.966
|
SECONDARY outcome
Timeframe: Baseline, week 4, week 12, week 24, week 48Population: 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 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.
Outcome measures
| Measure |
INC424
n=48 Participants
Patients diagnosed with PMF, PPV MF, or PET-MF were treated with oral INC424 at a dose of 15 - 20 mg (dose based on Baseline platelet count) twice daily.
|
|---|---|
|
Change From Baseline in EQ5D Preference Index (5 Level EuroQol Questionnaire Determining Quality of Life) From Baseline
week 4 (n=40)
|
0.06 unit on a scale
Standard Deviation 0.173
|
|
Change From Baseline in EQ5D Preference Index (5 Level EuroQol Questionnaire Determining Quality of Life) From Baseline
week 12 (n=38)
|
0.05 unit on a scale
Standard Deviation 0.178
|
|
Change From Baseline in EQ5D Preference Index (5 Level EuroQol Questionnaire Determining Quality of Life) From Baseline
week 24 (n=34)
|
0.05 unit on a scale
Standard Deviation 0.231
|
|
Change From Baseline in EQ5D Preference Index (5 Level EuroQol Questionnaire Determining Quality of Life) From Baseline
week 48 (n=29)
|
0.03 unit on a scale
Standard Deviation 0.222
|
SECONDARY outcome
Timeframe: week 12, week 24, week 26, week 48Population: 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.
Medical resource utilization (MRU) was assessed according to the number of hospitalizations.
Outcome measures
| Measure |
INC424
n=48 Participants
Patients diagnosed with PMF, PPV MF, or PET-MF were treated with oral INC424 at a dose of 15 - 20 mg (dose based on Baseline platelet count) twice daily.
|
|---|---|
|
Number of Hospitalizations
week 12 (n=48)
|
0.10 number of hospitalizations
Standard Deviation 0.371
|
|
Number of Hospitalizations
week 24 (n=40)
|
0.03 number of hospitalizations
Standard Deviation 0.158
|
|
Number of Hospitalizations
week 36 (n=37)
|
0.05 number of hospitalizations
Standard Deviation 0.229
|
|
Number of Hospitalizations
week 48 (n=35)
|
0.09 number of hospitalizations
Standard Deviation 0.284
|
SECONDARY outcome
Timeframe: week 48Population: 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 mean duration of hospitalization visits.
Outcome measures
| Measure |
INC424
n=9 Participants
Patients diagnosed with PMF, PPV MF, or PET-MF were treated with oral INC424 at a dose of 15 - 20 mg (dose based on Baseline platelet count) twice daily.
|
|---|---|
|
Duration of Hospitalizations
|
9.00 days
Standard Deviation 5.852
|
SECONDARY outcome
Timeframe: baseline to week 12, week 12 to week 24, week 24 to week 36, week 36 to week 48Population: 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 accidents and emergency room visits.
Outcome measures
| Measure |
INC424
n=48 Participants
Patients diagnosed with PMF, PPV MF, or PET-MF were treated with oral INC424 at a dose of 15 - 20 mg (dose based on Baseline platelet count) twice daily.
|
|---|---|
|
Number of Accident & Emergency Visits From Baseline
baseline to week 12 (n=48)
|
0.00 Number of visits
Full Range 0.412 • Interval 0.0 to 2.0
|
|
Number of Accident & Emergency Visits From Baseline
week 12 to week 24 (n=39)
|
0.00 Number of visits
Full Range 0.160 • Interval 0.0 to 1.0
|
|
Number of Accident & Emergency Visits From Baseline
week 24 to week 36 (n=33)
|
0.00 Number of visits
Full Range 0.415 • Interval 0.0 to 2.0
|
|
Number of Accident & Emergency Visits From Baseline
week 36 to week 48 (n=33)
|
0.00 Number of visits
Full Range 0.242 • Interval 0.0 to 1.0
|
SECONDARY outcome
Timeframe: baseline to week 12, week 12 to, week 24, week 24 to week 36, week 36 to week 48Population: 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.
Outcome measures
| Measure |
INC424
n=48 Participants
Patients diagnosed with PMF, PPV MF, or PET-MF were treated with oral INC424 at a dose of 15 - 20 mg (dose based on Baseline platelet count) twice daily.
|
|---|---|
|
Number of General Practitioner (GP), Specialists' and Urgent Care Visits
GP visits, week 12 to week 24 (n=36)
|
0.0 number of visits
Interval 0.0 to 1.0
|
|
Number of General Practitioner (GP), Specialists' and Urgent Care Visits
GP visits, baseline to week 12 (n=45)
|
0.0 number of visits
Interval 0.0 to 4.0
|
|
Number of General Practitioner (GP), Specialists' and Urgent Care Visits
GP visits, week 24 to week 36 (n=33)
|
0.0 number of visits
Interval 0.0 to 2.0
|
|
Number of General Practitioner (GP), Specialists' and Urgent Care Visits
GP visits, week 36 to week 48 (n=33)
|
0.0 number of visits
Interval 0.0 to 3.0
|
|
Number of General Practitioner (GP), Specialists' and Urgent Care Visits
Specialists visits, baseline to week 12 (n=47)
|
0.00 number of visits
Interval 0.0 to 8.0
|
|
Number of General Practitioner (GP), Specialists' and Urgent Care Visits
Specialists visits, week 12 to week 24 (n=36)
|
0.00 number of visits
Interval 0.0 to 2.0
|
|
Number of General Practitioner (GP), Specialists' and Urgent Care Visits
Specialists visits, week 24 to week 36 (n=33)
|
0.00 number of visits
Interval 0.0 to 4.0
|
|
Number of General Practitioner (GP), Specialists' and Urgent Care Visits
Specialists visits, week 36 to week 48 (n=33)
|
0.00 number of visits
Interval 0.0 to 3.0
|
|
Number of General Practitioner (GP), Specialists' and Urgent Care Visits
Urgent care visits, baseline to week 12 (n=48)
|
0.00 number of visits
Interval 0.0 to 1.0
|
|
Number of General Practitioner (GP), Specialists' and Urgent Care Visits
Urgent care visits, week 12 to week 24 (n=39)
|
0.00 number of visits
Interval 0.0 to 0.0
|
|
Number of General Practitioner (GP), Specialists' and Urgent Care Visits
Urgent care visits, week 24 to week 36 (n=33)
|
0.00 number of visits
Interval 0.0 to 1.0
|
|
Number of General Practitioner (GP), Specialists' and Urgent Care Visits
Urgent care visits, week 36 to week 48 (n=33)
|
0.00 number of visits
Interval 0.0 to 1.0
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
INC424
n=48 Participants
Patients diagnosed with PMF, PPV MF, or PET-MF were treated with oral INC424 at a dose of 15 - 20 mg (dose based on Baseline platelet count) twice daily.
|
|---|---|
|
Percentage of Participants With Transfusion Dependency Status
From independency at BL to independency at EOT
|
0.0 Percentage of participants
|
|
Percentage of Participants With Transfusion Dependency Status
From dependency at BL to independency at EOT
|
2.1 Percentage of participants
|
|
Percentage of Participants With Transfusion Dependency Status
From missing at BL to independency at EOT
|
0.0 Percentage of participants
|
|
Percentage of Participants With Transfusion Dependency Status
From independency at BL to dependency at EOT
|
0.0 Percentage of participants
|
|
Percentage of Participants With Transfusion Dependency Status
From dependency at BL to dependency at EOT
|
10.4 Percentage of participants
|
|
Percentage of Participants With Transfusion Dependency Status
From missing at BL to dependency at EOT
|
35.4 Percentage of participants
|
|
Percentage of Participants With Transfusion Dependency Status
From independency at BL to missing at EOT
|
0.0 Percentage of participants
|
|
Percentage of Participants With Transfusion Dependency Status
From dependency at BL to missing at EOT
|
0.0 Percentage of participants
|
|
Percentage of Participants With Transfusion Dependency Status
From missing at BL to missing at EOT
|
52.1 Percentage of participants
|
Adverse Events
INC424
Serious adverse events
| Measure |
INC424
n=48 participants at risk
Patients diagnosed with PMF, PPV MF, or PET-MF were treated with oral INC424 at a dose of 15 - 20 mg (dose based on Baseline platelet count) twice daily.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
6.2%
3/48
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
2.1%
1/48
|
|
Blood and lymphatic system disorders
Splenomegaly
|
4.2%
2/48
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
2.1%
1/48
|
|
Cardiac disorders
Atrial fibrillation
|
2.1%
1/48
|
|
Eye disorders
Cataract
|
2.1%
1/48
|
|
Eye disorders
Eyelid ptosis
|
2.1%
1/48
|
|
Gastrointestinal disorders
Abdominal pain
|
4.2%
2/48
|
|
Gastrointestinal disorders
Diarrhoea
|
2.1%
1/48
|
|
Gastrointestinal disorders
Dysphagia
|
2.1%
1/48
|
|
Gastrointestinal disorders
Vomiting
|
2.1%
1/48
|
|
General disorders
Hernia
|
2.1%
1/48
|
|
General disorders
Pyrexia
|
2.1%
1/48
|
|
Infections and infestations
Bronchopneumonia
|
2.1%
1/48
|
|
Infections and infestations
Infected skin ulcer
|
2.1%
1/48
|
|
Infections and infestations
Kidney infection
|
2.1%
1/48
|
|
Infections and infestations
Lower respiratory tract infection
|
2.1%
1/48
|
|
Infections and infestations
Progressive multifocal leukoencephalopathy
|
2.1%
1/48
|
|
Infections and infestations
Staphylococcal sepsis
|
4.2%
2/48
|
|
Injury, poisoning and procedural complications
Fall
|
2.1%
1/48
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
2.1%
1/48
|
|
Nervous system disorders
Dizziness
|
2.1%
1/48
|
|
Nervous system disorders
Dysarthria
|
2.1%
1/48
|
|
Nervous system disorders
Migraine
|
2.1%
1/48
|
|
Nervous system disorders
VIIth nerve paralysis
|
2.1%
1/48
|
|
Psychiatric disorders
Disorientation
|
2.1%
1/48
|
|
Renal and urinary disorders
Renal impairment
|
2.1%
1/48
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
2.1%
1/48
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
2.1%
1/48
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
4.2%
2/48
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
2.1%
1/48
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
2.1%
1/48
|
|
Surgical and medical procedures
Cataract operation
|
2.1%
1/48
|
Other adverse events
| Measure |
INC424
n=48 participants at risk
Patients diagnosed with PMF, PPV MF, or PET-MF were treated with oral INC424 at a dose of 15 - 20 mg (dose based on Baseline platelet count) twice daily.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
41.7%
20/48
|
|
Blood and lymphatic system disorders
Neutropenia
|
6.2%
3/48
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
35.4%
17/48
|
|
Gastrointestinal disorders
Abdominal distension
|
6.2%
3/48
|
|
Gastrointestinal disorders
Abdominal pain
|
22.9%
11/48
|
|
Gastrointestinal disorders
Abdominal pain upper
|
6.2%
3/48
|
|
Gastrointestinal disorders
Constipation
|
6.2%
3/48
|
|
Gastrointestinal disorders
Diarrhoea
|
22.9%
11/48
|
|
Gastrointestinal disorders
Mouth ulceration
|
8.3%
4/48
|
|
Gastrointestinal disorders
Nausea
|
14.6%
7/48
|
|
Gastrointestinal disorders
Vomiting
|
8.3%
4/48
|
|
General disorders
Fatigue
|
22.9%
11/48
|
|
General disorders
Pyrexia
|
10.4%
5/48
|
|
Infections and infestations
Lower respiratory tract infection
|
14.6%
7/48
|
|
Infections and infestations
Nasopharyngitis
|
6.2%
3/48
|
|
Infections and infestations
Upper respiratory tract infection
|
10.4%
5/48
|
|
Infections and infestations
Urinary tract infection
|
16.7%
8/48
|
|
Injury, poisoning and procedural complications
Contusion
|
22.9%
11/48
|
|
Injury, poisoning and procedural complications
Fall
|
12.5%
6/48
|
|
Investigations
Alanine aminotransferase increased
|
8.3%
4/48
|
|
Investigations
Platelet count decreased
|
6.2%
3/48
|
|
Investigations
Weight increased
|
6.2%
3/48
|
|
Metabolism and nutrition disorders
Gout
|
10.4%
5/48
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
8.3%
4/48
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
12.5%
6/48
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
6.2%
3/48
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
14.6%
7/48
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
8.3%
4/48
|
|
Nervous system disorders
Dizziness
|
18.8%
9/48
|
|
Nervous system disorders
Headache
|
22.9%
11/48
|
|
Nervous system disorders
Lethargy
|
20.8%
10/48
|
|
Nervous system disorders
Paraesthesia
|
6.2%
3/48
|
|
Psychiatric disorders
Depression
|
6.2%
3/48
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
10.4%
5/48
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
12.5%
6/48
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
25.0%
12/48
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
6.2%
3/48
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
6.2%
3/48
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
12.5%
6/48
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
10.4%
5/48
|
Additional Information
Study Director
Novartis Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER