Study of Oral SKI-O-703, SYK Inhibitor, in Patients With Persistent and Chronic Immune Thrombocytopenia (ITP)
- Conditions
- Immune Thrombocytopenia
- Interventions
- Drug: Placebo oral tablet
- Registration Number
- NCT04056195
- Lead Sponsor
- Oscotec Inc.
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 61
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description SKI-O-703 200 mg SKI-O-703 2 capsules of 100 mg SKI-O-703 BID (twice a day) 12 hours apart + 2 capsules of placebo during 12 weeks SKI-O-703 200 mg Placebo oral tablet 2 capsules of 100 mg SKI-O-703 BID (twice a day) 12 hours apart + 2 capsules of placebo during 12 weeks Placebo Placebo oral tablet 4 capsules of placebo during 12 weeks SKI-O-703 400 mg SKI-O-703 4 capsules of 100 mg SKI-O-703 + 0 capsules of placebo during 12 weeks
- Primary Outcome Measures
Name Time Method Platelet Response Up to week 12 Platelet count \>= 30,000/µL and doubling the baseline (average of 2 previous counts)
- Secondary Outcome Measures
Name Time Method Number of Participants With Vital Sign Abnormalities Up to week 16 Vital sign measurements considered to be clinically significant in the medical and scientific judgement of the investigator are recorded as AEs.
Number of Participants With 12-lead Electrocardiogram (ECG) Abnormalities Up to week 16 12-lead electrocardiogram (ECG) abnormalities that were recorded as adverse events
Number of Participants With Physical Examination Abnormalities Up to week 16 Physical examination abnormalities that were recorded as adverse events
Quality of Life Score Up to week 16 Qualtiy of Life as measured by the Short Form Questionnaire (SF-36) consists of eight health domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health. Scale scores range 0-100 scores (theoritically), with higher scores indicating better health.
Each health domain score contributes to the Physical Component Summary(PCS) and Mental Component Summary(MCS) scores. Both PCS and MCS are summary scores that are calculated using associated factor weights for the respective summary score applied to all eight scales.
For overall ranges for PCS and MCS (no theoretical full range available), the SF-36 verion 2 utilizes norm-based scoring involving a linear T-score transformation method so that scores for each of the health domain and component summary measures have a mean of 50 and a standard deviation of 10, based on 2009 U.S. general population. Scores above and below 50 are above and velow the average.Consecutive Increased Platelet Counts (≥2 Consecutive PLT ≥ 30,000/µL) Up to week 12 Proportion of participants achieving two or more consecutive platelet counts of ≥ 30,000/μL separated by at least 5 days and without the use of rescue medication
Consecutive Increased Platelet Counts (≥2 Consecutive PLT ≥ 50,000/µL) Up to week 12 Proportion of participants achieving two or more consecutive platelet counts of ≥ 50,000/μL separated by at least 5 days and without the use of rescue medication
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Discontinuation Up to week 16 The number of participants with Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs leading to Discontinuation each.
Trial Locations
- Locations (27)
Duke University Medical Center, 2301 Erwin Road
🇺🇸Durham, North Carolina, United States
The Cleveland Clinic Foundation, 9500 Euclid Avenue
🇺🇸Cleveland, Ohio, United States
Hospital Universitario Quironsalud Madrid, Calle Diego De Velazquez 1
🇪🇸Pozuelo De Alarcón, Madrid, Spain
Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii, Smoluchowskiego 17
🇵🇱Gdańsk, Poland
Copernicus PL Sp. z o.o. Wojewodzkie Centrum Onkologii, Aleja Zwyciestwa 31/32
🇵🇱Gdańsk, Poland
University General Hospital of Patras, Department of Internal Medicine, Hematology Division, Rio Patra
🇬🇷Patras, Achaia, Greece
University Hospital of Larissa, Mezourlo
🇬🇷Larissa, Greece
Georgios Papanikolaou General Hospital of Thessaloniki, Exohi
🇬🇷Thessaloníki, Greece
Hippokration Hospital, Konstantinoupoleos 49
🇬🇷Thessaloníki, Greece
Samsung Medical Center PPDS, 81 Irwon-dong Gangnam-gu
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital, 101 Daehak-ro, Jongno-gu
🇰🇷Soeul, Korea, Republic of
Severance Hospital Yonsei University Health System, 50-1 Yonsei-Ro, Seodaemun-Gu
🇰🇷Soeul, Korea, Republic of
Hospital Universitario 12 de Octubre, Avenida de Cordoba, s/n
🇪🇸Madrid, Spain
Hospital Universitario La Paz, Paseo Castellana 261
🇪🇸Madrid, Spain
Complejo Asistencial Universitario de Salamanca - H. Clinico, Paseo de San Vincent, 58
🇪🇸Salamanca, Spain
Hospital Universitario Virgen del Rocio, Avenida Manuel Siurot, Centro de Diagnostico y Tratamiento
🇪🇸Sevilla, Spain
University of Southern California, 1441 Eastlake Ave.
🇺🇸Los Angeles, California, United States
East Carolina University, 600 Moye Boulevard
🇺🇸Greenville, North Carolina, United States
Laiko General Hsoptial of Athens, 16 Sevastoupoleos Street
🇬🇷Athens, Attiki, Greece
AHEPA University General Hospital of Thessaloniki, Kyriakidi Stilponos 1
🇬🇷Thessaloníki, Greece
Ajou University Hospital, 164 World Cup-ro, Yeongtong-gu
🇰🇷Suwon-si, Gyeonggido, Korea, Republic of
Asan Medical Center - PPDS, 88 Olympic-ro 43-gil, Songpa-gu
🇰🇷Seoul, Korea, Republic of
Szpital Uniwersytecki Nr 2 im. Dr Jana Biziela w Bydgoszczy, Ujejskiego 75
🇵🇱Bydgoszcz, Poland
EMC Instytut Medyczny S.A Przychondnia przy Łowieckiej, Łowiecka
🇵🇱Wrocław, Poland
Hospital Universitario Ramon y Cajal, Carretera de Colmenar Viejo Km. 9100
🇪🇸Madrid, Spain
Hosptial Regional Universitario de Malaga - Hospital General, Avenida Carlos Haya, s/n
🇪🇸Málaga, Spain
Hospital Universitari i Politecnic La Fe de Valencia, Avda Fernando Abril Martorell no° 106
🇪🇸Valencia, Spain