Study of Oral SKI-O-703, SYK Inhibitor, in Patients With Persistent and Chronic Immune Thrombocytopenia (ITP)

Study Overview
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Brief Summary
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Study in patients with persistent and chronic Immune Thrombocytopenia (ITP), who have failed to respond or relapsed after prior therapy, with a platelet count <30,000/µL. Patient will be randomly assigned in 2 groups with two dose levels of SKI-O-703 200mg BID, 400 mg BID, and placebo; administered orally twice a day.

Detailed Description
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This study will evaluate the efficacy, safety, tolerability,pharmacokinetics (PK), and pharmacodynamics (PD) of select (200 mg BID and 400 mg BID) doses of SKI-O-703 in persistent and chronic ITP patients who have failed to respond or relapsed after prior therapy, with a platelet count <30,000/µL. on 2 occasions at least 7 days apart with the confirmatory count on the first day of treatment. subjects will participate in 3 treatment groups (24 subjects in each of the active treatment groups and 12 subjects in the placebo group). The total study duration will be 20 weeks per subject, which consists of up to 4 weeks of screening period, 12 weeks of treatment period, and 4 weeks of follow-up period.

Official Title
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A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Dose Study to Evaluate the Efficacy and Safety of Oral SKI-O-703, SYK Inhibitor, in Patients With Persistent and Chronic Immune Thrombocytopenia (ITP)

Conditions
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Immune Thrombocytopenia

Intervention / Treatment
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* Drug: SKI-O-703
* Drug: Placebo oral tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of primary ITP (persistent or chronic) Failed to respond or relapsed after at least 1 prior therapy, with a platelet count of <30,000/µL on 2 occasions at least 7 days apart with the confirmatory count on the first day of treatment Adequate hematologic, hepatic, and renal function ECOG performance status of 0, 1, or 2 Male and female subjects, the subject and their partners of childbearing potential agree to use medically acceptable methods of contraception during the study and for 6 months following discontinuation of study drug (excluding women who are not of childbearing potential and men who have been sterilized. Men who have been sterilized should be confirmed to have negative sperm count on 2 consecutive occasions.) Male subjects agree not to donate sperm for 90 days after the last dose of study drug Female subjects have negative pregnancy tests at Screening. Exclusion Criteria: History of current, active malignancy requiring or likely to require chemotherapeutic or surgical treatment during the study, with the exception of non-melanoma skin cancer, carcinoma in situ of the cervix, and localized prostate cancer managed by active surveillance Transfusion with blood or blood products or plasmapheresis within 2 weeks before the first administration of study drug History of known inherited coagulopathy, or recent arterial or deep venous thrombosis within the preceding 6 months Change in corticosteroid or immunosuppressant dose within 2 weeks prior to Day 1 Treatment with thrombopoietin receptor agonists within 2 weeks before Day 1 Treatment with rituximab or splenectomy within the 8 weeks prior to Day 1 Treatment with intravenous immunoglobulins (IVIGs) within 4 weeks prior to Day 1 Acute infection requiring oral antibiotics within 2 weeks Infections requiring intravenous antibiotics or hospitalization within 3 months Positive test results at Screening for human immunodeficiency virus, hepatitis B surface antigen, or hepatitis C virus antibody or positive result for hepatitis B core antibody with a negative result for hepatitis B surface antigen Received live vaccine within 28 days prior to Day 1 or plan to receive one during the study History or presence of any gastrointestinal, hepatic, or renal disease or any other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs Uncontrolled hypertension Subject had 12-lead electrocardiogram (ECG) findings of corrected QT interval by Fridericia formula (QTcF) > 450 msec (males) or > 470 msec (females), cardiac arrhythmias, or clinically significant cardiac or ECG abnormalities Subject received any investigational medication within 30 days or 5 half-lives - Concomitant use of any anticoagulants and platelet aggregation inhibiting drugs including aspirin (within 14 days of planned dosing through end of follow-up) Female subject who is currently pregnant or breastfeeding Prior treatment with a SYK inhibitor Planned surgery in the time frame of the dosing period.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SKI-O-703 200 mg<br>2 capsules of 100 mg SKI-O-703 BID (twice a day) 12 hours apart + 2 capsules of placebo during 12 weeks | Drug: SKI-O-703<br>* The SKI-O-703 capsules will contain 100 mg of drug substance.<br>Drug: Placebo oral tablet<br>* Placebo capsules are filled with microcrystalline cellulose.<br>|
| Experimental: SKI-O-703 400 mg<br>4 capsules of 100 mg SKI-O-703 + 0 capsules of placebo during 12 weeks | Drug: SKI-O-703<br>* The SKI-O-703 capsules will contain 100 mg of drug substance.<br>|
| Placebo Comparator: Placebo<br>4 capsules of placebo during 12 weeks | Drug: Placebo oral tablet<br>* Placebo capsules are filled with microcrystalline cellulose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Platelet Response | Platelet count >= 30,000/µL and doubling the baseline (average of 2 previous counts) | Up to week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs leading to Discontinuation |  | Up to week 16 | 
| Number of participants with vital sign abnormalities |  | Up to week 16 | 
| Number of participants with 12-lead electrocardiogram (ECG) abnormalities |  | Up to week 16 | 
| Number of participants with physical examination abnormalities |  | Up to week 16 | 
| Number of participants with clinical laboratory abnormalities |  | Up to week 16 | 
| Bleeding score | Measured by Immune thrombocytopenic purpura (ITP) bleeding score (Br. J. Haematol 2007;138(2): 245-8) | Up to week 16 | 
| Quality of Life score | Measured by the SF-36 score | Up to week 16 |