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

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 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.

Study Overview

• Status: Completed
• Conditions: Immune Thrombocytopenia
• Intervention / Treatment: Drug: SKI-O-703; Drug: Placebo oral tablet

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.

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 2

Contacts and Locations

Study Locations

• Greece
  • Larissa, Greece, 41110
    • University Hospital of Larissa, Mezourlo
  • Thessaloníki, Greece, 54636
    • AHEPA University General Hospital of Thessaloniki, Kyriakidi Stilponos 1
  • Thessaloníki, Greece, 54642
    • Hippokration Hospital, Konstantinoupoleos 49
  • Thessaloníki, Greece, 57010
    • Georgios Papanikolaou General Hospital of Thessaloniki, Exohi
  • Achaia
    • Patras, Achaia, Greece, 26500
      • University General Hospital of Patras, Department of Internal Medicine, Hematology Division, Rio Patra
  • Attiki
    • Athens, Attiki, Greece, 11526
      • Laiko General Hsoptial of Athens, 16 Sevastoupoleos Street
• Korea, Republic of
  • Seoul, Korea, Republic of, 5505
    • Asan Medical Center - PPDS, 88 Olympic-ro 43-gil, Songpa-gu
  • Seoul, Korea, Republic of, 6351
    • Samsung Medical Center PPDS, 81 Irwon-dong Gangnam-gu
  • Soeul, Korea, Republic of, 3080
    • Seoul National University Hospital, 101 Daehak-Ro, Jongno-Gu
  • Soeul, Korea, Republic of, 3722
    • Severance Hospital Yonsei University Health System, 50-1 Yonsei-Ro, Seodaemun-Gu
  • Gyeonggido
    • Suwon-si, Gyeonggido, Korea, Republic of, 16499
      • Ajou University Hospital, 164 World Cup-ro, Yeongtong-gu
• Poland
  • Bydgoszcz, Poland, 85-168
    • Szpital Uniwersytecki Nr 2 im. Dr Jana Biziela w Bydgoszczy, Ujejskiego 75
  • Gdańsk, Poland, 80-214
    • Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii, Smoluchowskiego 17
  • Gdańsk, Poland, 80-219
    • Copernicus PL Sp. z o.o. Wojewodzkie Centrum Onkologii, Aleja Zwyciestwa 31/32
  • Wrocław, Poland
    • EMC Instytut Medyczny S.A Przychondnia przy Łowieckiej, Łowiecka
• Spain
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal, Carretera de Colmenar Viejo Km. 9100
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre, Avenida de Cordoba, s/n
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz, Paseo Castellana 261
  • Málaga, Spain, 29010
    • Hosptial Regional Universitario de Malaga - Hospital General, Avenida Carlos Haya, s/n
  • Salamanca, Spain, 37007
    • Complejo Asistencial Universitario de Salamanca - H. Clinico, Paseo de San Vincent, 58
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio, Avenida Manuel Siurot, Centro de Diagnostico y Tratamiento
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe de Valencia, Avda Fernando Abril Martorell no° 106
  • Madrid
    • Pozuelo De Alarcón, Madrid, Spain, 28223
      • Hospital Universitario Quironsalud Madrid, Calle Diego De Velazquez 1
• United States
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California, 1441 Eastlake Ave.
  • North Carolina
    • Durham, North Carolina, United States, 22705
      • Duke University Medical Center, 2301 Erwin Road
    • Greenville, North Carolina, United States, 27834
      • East Carolina University, 600 Moye Boulevard
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation, 9500 Euclid Avenue

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SKI-O-703 200 mg; 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; The SKI-O-703 capsules will contain 100 mg of drug substance.; Drug: Placebo oral tablet; Placebo capsules are filled with microcrystalline cellulose.
Experimental: SKI-O-703 400 mg; 4 capsules of 100 mg SKI-O-703 + 0 capsules of placebo during 12 weeks	Drug: SKI-O-703; The SKI-O-703 capsules will contain 100 mg of drug substance.
Placebo Comparator: Placebo; 4 capsules of placebo during 12 weeks	Drug: Placebo oral tablet; Placebo capsules are filled with microcrystalline cellulose.

What is the study measuring?

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	The number of participants with Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs leading to Discontinuation each.	Up to week 16
Number of Participants With Vital Sign Abnormalities	Vital sign measurements considered to be clinically significant in the medical and scientific judgement of the investigator are recorded as AEs.	Up to week 16
Number of Participants With 12-lead Electrocardiogram (ECG) Abnormalities	12-lead electrocardiogram (ECG) abnormalities that were recorded as adverse events	Up to week 16
Number of Participants With Physical Examination Abnormalities	Physical examination abnormalities that were recorded as adverse events	Up to week 16
Quality of Life Score	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.	Up to week 16
Consecutive Increased Platelet Counts (≥2 Consecutive PLT ≥ 30,000/µL)	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	Up to week 12
Consecutive Increased Platelet Counts (≥2 Consecutive PLT ≥ 50,000/µL)	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	Up to week 12

Collaborators and Investigators

• Sponsor: Oscotec Inc.

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2019
• Primary Completion (Actual): January 10, 2023
• Study Completion (Actual): January 10, 2023

Study Registration Dates

• First Submitted: August 12, 2019
• First Submitted That Met QC Criteria: August 12, 2019
• First Posted (Actual): August 14, 2019

Study Record Updates

• Last Update Posted (Actual): July 10, 2024
• Last Update Submitted That Met QC Criteria: July 9, 2024
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Hemorrhage; Hemorrhagic Disorders; Blood Coagulation Disorders; Skin Manifestations; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura, Thrombocytopenic; Purpura; Cytopenia; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia
• Other Study ID Numbers: OSCO-P2101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No