Clinical trial NCT04056195: Study of Oral SKI-O-703, SYK Inhibitor, in Patients With Persistent and Chronic Immune Thrombocytopenia (ITP)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Immune Thrombocytopenia
Lead sponsor: Oscotec Inc.
Sponsor class: INDUSTRY
First posted: 2019-08-14
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Platelet Response
timeFrame: Up to week 12
Secondary outcomes:
measure: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Discontinuation
timeFrame: Up to week 16
measure: Number of Participants With Vital Sign Abnormalities
timeFrame: Up to week 16
measure: Number of Participants With 12-lead Electrocardiogram (ECG) Abnormalities
timeFrame: Up to week 16
measure: Number of Participants With Physical Examination Abnormalities
timeFrame: Up to week 16
measure: Quality of Life Score
timeFrame: Up to week 16
measure: Consecutive Increased Platelet Counts (≥2 Consecutive PLT ≥ 30,000/µL)
timeFrame: Up to week 12
measure: Consecutive Increased Platelet Counts (≥2 Consecutive PLT ≥ 50,000/µL)
timeFrame: Up to week 12
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California, 1441 Eastlake Ave.
state: California
city: Durham
country: United States
facility: Duke University Medical Center, 2301 Erwin Road
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University, 600 Moye Boulevard
state: North Carolina
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation, 9500 Euclid Avenue
state: Ohio
city: Patras
country: Greece
facility: University General Hospital of Patras, Department of Internal Medicine, Hematology Division, Rio Patra
state: Achaia
city: Athens
country: Greece
facility: Laiko General Hsoptial of Athens, 16 Sevastoupoleos Street
state: Attiki
city: Larissa
country: Greece
facility: University Hospital of Larissa, Mezourlo
city: Thessaloníki
country: Greece
facility: AHEPA University General Hospital of Thessaloniki, Kyriakidi Stilponos 1
city: Thessaloníki
country: Greece
facility: Hippokration Hospital, Konstantinoupoleos 49
city: Thessaloníki
country: Greece
facility: Georgios Papanikolaou General Hospital of Thessaloniki, Exohi
city: Suwon-si
country: Korea, Republic of
facility: Ajou University Hospital, 164 World Cup-ro, Yeongtong-gu
state: Gyeonggido
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center - PPDS, 88 Olympic-ro 43-gil, Songpa-gu
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center PPDS, 81 Irwon-dong Gangnam-gu
city: Soeul
country: Korea, Republic of
facility: Seoul National University Hospital, 101 Daehak-ro, Jongno-gu
city: Soeul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System, 50-1 Yonsei-Ro, Seodaemun-Gu
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki Nr 2 im. Dr Jana Biziela w Bydgoszczy, Ujejskiego 75
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii, Smoluchowskiego 17
city: Gdańsk
country: Poland
facility: Copernicus PL Sp. z o.o. Wojewodzkie Centrum Onkologii, Aleja Zwyciestwa 31/32
city: Wrocław
country: Poland
facility: EMC Instytut Medyczny S.A Przychondnia przy Łowieckiej, Łowiecka
city: Pozuelo De Alarcón
country: Spain
facility: Hospital Universitario Quironsalud Madrid, Calle Diego De Velazquez 1
state: Madrid
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal, Carretera de Colmenar Viejo Km. 9100
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre, Avenida de Cordoba, s/n
city: Madrid
country: Spain
facility: Hospital Universitario La Paz, Paseo Castellana 261
city: Málaga
country: Spain
facility: Hosptial Regional Universitario de Malaga - Hospital General, Avenida Carlos Haya, s/n
city: Salamanca
country: Spain
facility: Complejo Asistencial Universitario de Salamanca - H. Clinico, Paseo de San Vincent, 58
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio, Avenida Manuel Siurot, Centro de Diagnostico y Tratamiento
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia, Avda Fernando Abril Martorell no° 106
Study officials:
References: