Trial Outcomes & Findings for A Efficacy and Safety Study of R935788 in the Treatment of Persistent/Chronic Immune Thrombocytopenic Purpura (ITP) (NCT NCT02076399)

NCT ID: NCT02076399

Last Updated: 2019-02-12

Results Overview

A stable platelet response by Week 24 defined as a platelet count of at least 50,000/μL on at least 4 of the last 6 scheduled visits between Weeks 14 and 24

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 76 participants
• Primary outcome timeframe: From Week 14 to Week 24
• Results posted on: 2019-02-12

Participant Flow

76 patients were enrolled from July 2014 to April 2016

Participant milestones

Measure	Fostamatinib Recipient Fostamatinib (100 mg PO bid or 150 mg PO bid)	Placebo Recipient Placebo
Overall Study STARTED	51	25
Overall Study COMPLETED	12	1
Overall Study NOT COMPLETED	39	24

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Efficacy and Safety Study of R935788 in the Treatment of Persistent/Chronic Immune Thrombocytopenic Purpura (ITP)

Baseline characteristics by cohort

Measure	Fostamatinib Recipient n=51 Participants Fostamatinib (100 mg PO bid or 150 mg PO bid)	Placebo Recipient n=25 Participants Placebo	Total n=76 Participants Total of all reporting groups
Age, Continuous	57.3 years STANDARD_DEVIATION 17.7 • n=5 Participants	53.2 years STANDARD_DEVIATION 16.0 • n=7 Participants	56.0 years STANDARD_DEVIATION 17.2 • n=5 Participants
Sex: Female, Male Female	30 Participants n=5 Participants	17 Participants n=7 Participants	47 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants	8 Participants n=7 Participants	29 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	48 Participants n=5 Participants	24 Participants n=7 Participants	72 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	44 Participants n=5 Participants	21 Participants n=7 Participants	65 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: From Week 14 to Week 24

A stable platelet response by Week 24 defined as a platelet count of at least 50,000/μL on at least 4 of the last 6 scheduled visits between Weeks 14 and 24

Outcome measures

Measure	Fostamatinib Recipient n=51 Participants Fostamatinib (100 mg PO bid or 150 mg PO bid)	Placebo Recipient n=25 Participants Placebo
Number of Participants With Stable Platelet Response (Count of ≥50,000/µL on at Least 4 of the Last 6 Scheduled Visits Between Weeks 14 and 24)	9 Participants	0 Participants

SECONDARY outcome

Timeframe: Week 12

Platelet Count ≥ 50,000/µL at Week 12

Outcome measures

Measure	Fostamatinib Recipient n=51 Participants Fostamatinib (100 mg PO bid or 150 mg PO bid)	Placebo Recipient n=25 Participants Placebo
Number of Participants With Platelet Count ≥ 50,000/µL at Week 12	11 Participants	0 Participants

SECONDARY outcome

Timeframe: Week 24

Platelet Count ≥ 50,000/µL at Week 24

Outcome measures

Measure	Fostamatinib Recipient n=51 Participants Fostamatinib (100 mg PO bid or 150 mg PO bid)	Placebo Recipient n=25 Participants Placebo
Number of Participants With Platelet Count ≥ 50,000/µL at Week 24	8 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline to Week 12

Number of subjects with baseline platelet count <15,000/μL who showed platelet count increase to ≥30,000/μL and ≥20,000/μL from baseline count at Week 12.

Outcome measures

Measure	Fostamatinib Recipient n=25 Participants Fostamatinib (100 mg PO bid or 150 mg PO bid)	Placebo Recipient n=12 Participants Placebo
Platelet Count ≥ 30,000/μL and ≥ 20,000/μL Above Baseline in Subjects With Baseline Platelet Count of <15,000/μL at Week 12.	4 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline to Week 24

Number of subjects with baseline platelet count <15,000/μL who showed platelet count increase to ≥30,000/μL and ≥20,000/μL from baseline count at Week 24.

Outcome measures

Measure	Fostamatinib Recipient n=25 Participants Fostamatinib (100 mg PO bid or 150 mg PO bid)	Placebo Recipient n=12 Participants Placebo
Platelet Count ≥ 30,000/μL and ≥ 20,000/μL Above Baseline in Subjects With Baseline Platelet Count of <15,000/μL at Week 24.	4 Participants	0 Participants

SECONDARY outcome

Timeframe: Assessed over the 24-week study period

The ITP Bleeding Scale (IBLS) is an immune thrombocytopenic purpura (ITP)-specific bleeding score used to analyze the correlation of clinical and laboratory platelet variables with bleeding. The IBLS comprises of 11 grades from 0 (none) to 2 (marked bleeding) by history over the previous week or by exam; 2 being worse. These 11 grades include: skin by physical exam, oral by physical exam, skin by history, oral by history, epistaxis, gastrointestinal, urinary, gynecological, pulmonary, intracranial hemorrhage, and subconjunctival hemorrhage. After each grade is scored, the mean value for all 11 grades is calculated (lowest score being 0 and highest score being 2) for each subject visit. LOCF method was used to impute any missing data.

The mean of the IBLS scores across visits during the 24-week treatment period was summarized by treatment group using descriptive statistics. A 2-sided, 2-sample t-test was used to test for a difference in means between treatments for this endpoint.

Outcome measures

Measure	Fostamatinib Recipient n=51 Participants Fostamatinib (100 mg PO bid or 150 mg PO bid)	Placebo Recipient n=25 Participants Placebo
Mean of the ITP Bleeding Score (IBLS)	0.13 scores on a scale Standard Deviation 0.12	0.14 scores on a scale Standard Deviation 0.10

SECONDARY outcome

Timeframe: Assessed over the 24-week study period

The World Health Organization (WHO) bleeding scale is a standardized grading scale created to measure the severity of bleeding. The scale is a clinical investigator-assessed five-point scale with a score range starting at the lowest 0=No bleeding, 1 = Petechiae, 2=Mild blood loss, 3=Gross blood loss, to the worse 4=Debilitating blood loss. The WHO bleeding scale is scored by history over the previous-week or by exam. After each grade is scored, the mean value is calculated (lowest score being 0 [no bleeding] to the highest score being 4 [debilitating blood loss]) for each visit. LOCF method was used to impute any missing data.

The mean of the WHO bleeding scale across visits during the 24-week treatment period was summarized by treatment group using descriptive statistics. A 2-sided, 2-sample t-test was used to test for a difference in means between treatments for this endpoint.

Outcome measures

Measure	Fostamatinib Recipient n=51 Participants Fostamatinib (100 mg PO bid or 150 mg PO bid)	Placebo Recipient n=25 Participants Placebo
Mean of World Health Organization (WHO) Bleeding Scale	0.61 scores on a scale Standard Deviation 0.66	0.46 scores on a scale Standard Deviation 0.56

Adverse Events

Fostamatinib Recipient

Serious events: 8 serious events

Other events: 49 other events

Deaths: 0 deaths

Placebo Recipient

Serious events: 5 serious events

Other events: 19 other events

Deaths: 1 deaths

Serious adverse events

Measure	Fostamatinib Recipient n=51 participants at risk Fostamatinib (100 mg PO bid or 150 mg PO bid)	Placebo Recipient n=25 participants at risk Placebo
Blood and lymphatic system disorders Anaemia	0.00% 0/51 • 24 Weeks	4.0% 1/25 • Number of events 2 • 24 Weeks
Blood and lymphatic system disorders Febrile Neutropenia	2.0% 1/51 • Number of events 1 • 24 Weeks	0.00% 0/25 • 24 Weeks
Blood and lymphatic system disorders Immune Thrombocytopenic Purpura	2.0% 1/51 • Number of events 1 • 24 Weeks	0.00% 0/25 • 24 Weeks
Blood and lymphatic system disorders Thrombocytopenia	2.0% 1/51 • Number of events 2 • 24 Weeks	0.00% 0/25 • 24 Weeks
Cardiac disorders Cardiac Failure Congestive	0.00% 0/51 • 24 Weeks	4.0% 1/25 • Number of events 1 • 24 Weeks
Eye disorders Retinal Tear	2.0% 1/51 • Number of events 1 • 24 Weeks	0.00% 0/25 • 24 Weeks
Gastrointestinal disorders Diarrhoea	2.0% 1/51 • Number of events 1 • 24 Weeks	0.00% 0/25 • 24 Weeks
Gastrointestinal disorders Gastrointestinal Haemorrhage	0.00% 0/51 • 24 Weeks	4.0% 1/25 • Number of events 2 • 24 Weeks
Infections and infestations Pneumonia	2.0% 1/51 • Number of events 1 • 24 Weeks	0.00% 0/25 • 24 Weeks
Infections and infestations Sepsis	0.00% 0/51 • 24 Weeks	4.0% 1/25 • Number of events 1 • 24 Weeks
Nervous system disorders Syncope	2.0% 1/51 • Number of events 1 • 24 Weeks	0.00% 0/25 • 24 Weeks
Reproductive system and breast disorders Menorrhagia	0.00% 0/51 • 24 Weeks	4.0% 1/25 • Number of events 1 • 24 Weeks
Reproductive system and breast disorders Vaginal Haemorrhage	2.0% 1/51 • Number of events 1 • 24 Weeks	0.00% 0/25 • 24 Weeks
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary Disease	0.00% 0/51 • 24 Weeks	4.0% 1/25 • Number of events 1 • 24 Weeks
Respiratory, thoracic and mediastinal disorders Epistaxis	2.0% 1/51 • Number of events 2 • 24 Weeks	4.0% 1/25 • Number of events 1 • 24 Weeks

Other adverse events

Measure	Fostamatinib Recipient n=51 participants at risk Fostamatinib (100 mg PO bid or 150 mg PO bid)	Placebo Recipient n=25 participants at risk Placebo
Gastrointestinal disorders Diarrhoea	41.2% 21/51 • 24 Weeks	16.0% 4/25 • 24 Weeks
Gastrointestinal disorders Nausea	29.4% 15/51 • 24 Weeks	4.0% 1/25 • 24 Weeks
Gastrointestinal disorders Constipation	5.9% 3/51 • 24 Weeks	4.0% 1/25 • 24 Weeks
Gastrointestinal disorders Abdominal pain	5.9% 3/51 • 24 Weeks	0.00% 0/25 • 24 Weeks
Gastrointestinal disorders Flatulence	5.9% 3/51 • 24 Weeks	0.00% 0/25 • 24 Weeks
Gastrointestinal disorders Vomiting	3.9% 2/51 • 24 Weeks	8.0% 2/25 • 24 Weeks
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/51 • 24 Weeks	8.0% 2/25 • 24 Weeks
Investigations Alanine aminotransferase increased	17.6% 9/51 • 24 Weeks	0.00% 0/25 • 24 Weeks
Investigations Aspartate aminotransferase increased	15.7% 8/51 • 24 Weeks	0.00% 0/25 • 24 Weeks
Investigations Blood pressure increased	5.9% 3/51 • 24 Weeks	4.0% 1/25 • 24 Weeks
Nervous system disorders Headache	13.7% 7/51 • 24 Weeks	24.0% 6/25 • 24 Weeks
Nervous system disorders Dizziness	17.6% 9/51 • 24 Weeks	16.0% 4/25 • 24 Weeks
Nervous system disorders Dysgeusia	7.8% 4/51 • 24 Weeks	0.00% 0/25 • 24 Weeks
Respiratory, thoracic and mediastinal disorders Epistaxis	17.6% 9/51 • 24 Weeks	16.0% 4/25 • 24 Weeks
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.9% 3/51 • 24 Weeks	12.0% 3/25 • 24 Weeks
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	2.0% 1/51 • 24 Weeks	8.0% 2/25 • 24 Weeks
Infections and infestations Upper respiratory tract infection	9.8% 5/51 • 24 Weeks	4.0% 1/25 • 24 Weeks
Infections and infestations Urinary tract infection	5.9% 3/51 • 24 Weeks	0.00% 0/25 • 24 Weeks
General disorders Fatigue	11.8% 6/51 • 24 Weeks	4.0% 1/25 • 24 Weeks
General disorders Pyrexia	3.9% 2/51 • 24 Weeks	8.0% 2/25 • 24 Weeks
General disorders Chest pain	7.8% 4/51 • 24 Weeks	4.0% 1/25 • 24 Weeks
Vascular disorders Hypertension	25.5% 13/51 • 24 Weeks	4.0% 1/25 • 24 Weeks
Vascular disorders Rash	7.8% 4/51 • 24 Weeks	0.00% 0/25 • 24 Weeks
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/51 • 24 Weeks	8.0% 2/25 • 24 Weeks
Blood and lymphatic system disorders Anaemia	3.9% 2/51 • 24 Weeks	8.0% 2/25 • 24 Weeks
Injury, poisoning and procedural complications Contusion	5.9% 3/51 • 24 Weeks	0.00% 0/25 • 24 Weeks

Additional Information

Anne-Marie Duliege, MD

Rigel

Phone: 650-624-1100

Email: clinicaltrials@rigel.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place