Clinical Trials List
Protocol Number1423M0634
NCT Number(ClinicalTrials.gov Identfier)NCT02389621
2015-09-01 - 2016-07-31
Phase III
Terminated2
ICD-10D69.6
Thrombocytopenia, unspecified
ICD-9287.5
Thrombocytopenia, unspecified
A Phase 3 Randomised, Double-blind, Placebo-controlled Study to Assess the Safety and Efficacy of S-888711 (Lusutrombopag) for the Treatment of Thrombocytopenia in Patients with Chronic Liver Disease Undergoing Elective Invasive Procedures (L-PLUS 2)
-
Trial Applicant
IQVIA RDS Taiwan Ltd.
-
Sponsor
Shionogi Inc.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Ming-Lun Yeh Digestive System Department
- Ming-Lung Yu Digestive System Department
- Chia-Yen Dai Digestive System Department
- Jee-Fu Huang Digestive System Department
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- PEI-JER CHEN Digestive System Department
- Chen-Hua Liu Digestive System Department
- 楊宏志 Digestive System Department
- Jia-Horng Kao Digestive System Department
- 蘇東弘 Digestive System Department
The Actual Total Number of Participants Enrolled
0 Completed
Audit
None
Condition/Disease
Chronic Liver Disease (CLD)
Objectives
Primary Objective:
To compare the efficacy of S-888711 with placebo for the treatment of
thrombocytopenia in patients with CLD who are undergoing elective invasive
procedures
Secondary Objectives:
To assess the safety and tolerability of S-888711 treatment compared with placebo
To assess the platelet response following treatment with S-888711 compared with
placebo
To assess the pharmacodynamics (PD) and pharmacokinetics (PK) of S-888711
Test Drug
S-888711
Active Ingredient
Lusutrombopag
Dosage Form
tablet
Dosage
3mg
Endpoints
Primary endpoint:
Proportion of patients who require no platelet transfusion prior to the primary invasive
procedure and no rescue therapy for bleeding from randomisation through 7 days after
the primary elective procedure.
Secondary endpoints:
Proportion of patients who require no platelet transfusion during the study
Proportion of responders: patients who achieve a platelet count of ≥ 50 × 109
/L with an
increase of ≥ 20 × 109
/L from baseline at any time during the study
Duration of the platelet count defined as the number of days during which the platelet
count was maintained as ≥ 50 × 109
/L
Proportion of patients who require rescue therapy for bleeding at any time during the
study
Frequency of platelet transfusions
The change from baseline in platelet count over time (time course of platelet count)
Safety and tolerability
Assessment of plasma concentrations of S-888711
Proportion of patients who require no platelet transfusion prior to the primary invasive
procedure and no rescue therapy for bleeding from randomisation through 7 days after
the primary elective procedure.
Secondary endpoints:
Proportion of patients who require no platelet transfusion during the study
Proportion of responders: patients who achieve a platelet count of ≥ 50 × 109
/L with an
increase of ≥ 20 × 109
/L from baseline at any time during the study
Duration of the platelet count defined as the number of days during which the platelet
count was maintained as ≥ 50 × 109
/L
Proportion of patients who require rescue therapy for bleeding at any time during the
study
Frequency of platelet transfusions
The change from baseline in platelet count over time (time course of platelet count)
Safety and tolerability
Assessment of plasma concentrations of S-888711
Inclution Criteria
Inclusion Criteria:
Patients who fulfil the following criteria will be eligible for inclusion in the study:
1. Able to understand the study and comply with all the study procedures.
2. Willing to provide written informed consent prior to Screening.
3. Male or female.
4. 18 years of age or older at the time of signing informed consent.
5. CLD limited to Child-Pugh Class A and Class B disease (see Appendix 3).
6. Platelet count < 50 × 109
/L at baseline on Day 1 prior to randomisation.
7. Undergoing an elective invasive procedure that:
is likely to require administration of platelets
is expected to be performed between Days 9 and 14
does not include laparotomy, thoracotomy, craniotomy, open-heart surgery, organ
resection, or
does not include partial organ resection (however, biopsy and other types of tissue
removal will be allowed if risk of bleeding and invasiveness is considered
comparable or lower than those procedures in the list of example procedures; see
Appendix 4).
8. Eastern Cooperative Oncology Group (ECOG) performance status (PS) grade of 0 or
1 (see Appendix 5).
9. In the opinion of the investigator, able to meet the requirements of the study
10. Male patients who are sterile or who agree to use an appropriate method of
contraception (including use of a condom with spermicide) from Screening to
completion of the Post-treatment period.
11. Female patients who are not postmenopausal or surgically sterile need to agree to use
a highly effective contraception (including contraceptive implant, injectable
contraceptive, combination hormonal contraceptive [including vaginal rings],
intrauterine contraceptive device or vasectomised partner) from Screening to
completion of the Post-treatment period. Barrier method with or without spermicide,
double barrier contraception and oral contraceptive pill are insufficient methods on
their own.
Patients who fulfil the following criteria will be eligible for inclusion in the study:
1. Able to understand the study and comply with all the study procedures.
2. Willing to provide written informed consent prior to Screening.
3. Male or female.
4. 18 years of age or older at the time of signing informed consent.
5. CLD limited to Child-Pugh Class A and Class B disease (see Appendix 3).
6. Platelet count < 50 × 109
/L at baseline on Day 1 prior to randomisation.
7. Undergoing an elective invasive procedure that:
is likely to require administration of platelets
is expected to be performed between Days 9 and 14
does not include laparotomy, thoracotomy, craniotomy, open-heart surgery, organ
resection, or
does not include partial organ resection (however, biopsy and other types of tissue
removal will be allowed if risk of bleeding and invasiveness is considered
comparable or lower than those procedures in the list of example procedures; see
Appendix 4).
8. Eastern Cooperative Oncology Group (ECOG) performance status (PS) grade of 0 or
1 (see Appendix 5).
9. In the opinion of the investigator, able to meet the requirements of the study
10. Male patients who are sterile or who agree to use an appropriate method of
contraception (including use of a condom with spermicide) from Screening to
completion of the Post-treatment period.
11. Female patients who are not postmenopausal or surgically sterile need to agree to use
a highly effective contraception (including contraceptive implant, injectable
contraceptive, combination hormonal contraceptive [including vaginal rings],
intrauterine contraceptive device or vasectomised partner) from Screening to
completion of the Post-treatment period. Barrier method with or without spermicide,
double barrier contraception and oral contraceptive pill are insufficient methods on
their own.
Exclusion Criteria
Exclusion Criteria:
Patients who fulfil any of the following criteria will be excluded from the study:
1. Any of the following diseases:
haematopoietic tumour
aplastic anaemia
myelodysplastic syndrome
myelofibrosis
congenital thrombocytopenia
drug-induced thrombocytopenia
generalised infection requiring treatment except for viral liver disease
immune thrombocytopenia.
2. Any solid malignant tumour if:
the patient requires systemic chemotherapy or radiotherapy for that malignant
tumour during the study
the malignant tumour is associated with nodal metastasis, distant metastasis, or
invasion of the surrounding organs
The exceptions are:
- a malignant tumour that is the treatment target of the primary invasive
procedure
- non-melanoma skin cancer, intramucosal cancer, or carcinoma in situ not
requiring any treatment during the study.
3. History of splenectomy.
4. History of liver transplantation.
5. Any of the following at Screening:
hepatic encephalopathy uncontrolled by drugs
ascites uncontrolled by drugs.
6. Portal vein tumour embolism.
7. Known to be positive for the human immunodeficiency virus.
8. Past or present thrombosis or prothrombotic condition (eg, cerebral infarction,
myocardial infarction, angina pectoris, coronary artery stent placement, angioplasty,
coronary artery bypass grafting, congestive heart failure [New York Heart Association
{NYHA} Grade III/IV], arrhythmia known to increase the risk of thromboembolic
events [eg, atrial fibrillation], pulmonary thromboembolism, deep vein thrombosis, or
disseminated intravascular coagulation syndrome).
9. History or evidence of any of the following diseases:
congenital thrombotic disease (eg, antithrombin deficiency, protein C deficiency,
protein S deficiency, or coagulation factor [Factor V Leiden] mutation)
acquired thrombotic disease (eg, antiphospholipid antibody syndrome, paroxysmal
nocturnal haemoglobinuria, hyperhomocysteinaemia, or increased factor VIII)
Budd-Chiari syndrome.
10. Portal vein thrombosis based on ultrasound, computed tomography (CT), or magnetic
resonance imaging (MRI) within 28 days prior to randomisation or a history of portal
vein thrombosis.
11. Absence of hepatopetal blood flow in the main trunk of the portal vein as demonstrated
by Doppler ultrasonography within 28 days prior to randomisation.
12. Untreated gastro-oesophageal varices that are bleeding or require treatment based on
upper gastrointestinal endoscopy within 180 days prior to randomisation (except for
patients in whom the primary invasive procedure is for the treatment of
gastro-oesophageal varices).
13. History or evidence of disease associated with a risk of bleeding (eg, coagulation factor
deficiency or von Willebrand factor deficiency).
14. Bleeding score at randomisation ≥ Grade 2 according to the World Health
Organization (WHO) Bleeding Scale (see Appendix 7).
15. Any of the following drugs or therapies within 90 days prior to randomisation:
anticancer drugs except for transcatheter arterial chemoembolisation (TACE) and
lipiodolisation
interferon preparations
radiation therapy
exsanguination
other TPO receptor agonist
any investigational agent.
16. Any of the following invasive procedures within 90 days prior to randomisation:
laparotomy, thoracotomy, craniotomy, or open-heart surgery
procedures involving any organ resection or any partial organ resection (tissue
resection associated with an endoscopic examination is permitted)
partial splenic embolisation.
17. Any invasive procedure (except for the treatment of gastro-oesophageal varices)
within 14 days prior to randomisation.
18. Blood transfusion (except for red blood cell products and albumin preparations) within
14 days prior to randomisation.
19. Patients who have received S-888711 before.
20. Pregnant or lactating female.
21. Patients with known or suspected ongoing, active alcohol or substance abuse. Patients
with a recent history who the investigator feels are able to comply with the study
procedures and medications will be allowed to participate.
22. Considered ineligible by the investigator for any other reason.
Patients who fulfil any of the following criteria will be excluded from the study:
1. Any of the following diseases:
haematopoietic tumour
aplastic anaemia
myelodysplastic syndrome
myelofibrosis
congenital thrombocytopenia
drug-induced thrombocytopenia
generalised infection requiring treatment except for viral liver disease
immune thrombocytopenia.
2. Any solid malignant tumour if:
the patient requires systemic chemotherapy or radiotherapy for that malignant
tumour during the study
the malignant tumour is associated with nodal metastasis, distant metastasis, or
invasion of the surrounding organs
The exceptions are:
- a malignant tumour that is the treatment target of the primary invasive
procedure
- non-melanoma skin cancer, intramucosal cancer, or carcinoma in situ not
requiring any treatment during the study.
3. History of splenectomy.
4. History of liver transplantation.
5. Any of the following at Screening:
hepatic encephalopathy uncontrolled by drugs
ascites uncontrolled by drugs.
6. Portal vein tumour embolism.
7. Known to be positive for the human immunodeficiency virus.
8. Past or present thrombosis or prothrombotic condition (eg, cerebral infarction,
myocardial infarction, angina pectoris, coronary artery stent placement, angioplasty,
coronary artery bypass grafting, congestive heart failure [New York Heart Association
{NYHA} Grade III/IV], arrhythmia known to increase the risk of thromboembolic
events [eg, atrial fibrillation], pulmonary thromboembolism, deep vein thrombosis, or
disseminated intravascular coagulation syndrome).
9. History or evidence of any of the following diseases:
congenital thrombotic disease (eg, antithrombin deficiency, protein C deficiency,
protein S deficiency, or coagulation factor [Factor V Leiden] mutation)
acquired thrombotic disease (eg, antiphospholipid antibody syndrome, paroxysmal
nocturnal haemoglobinuria, hyperhomocysteinaemia, or increased factor VIII)
Budd-Chiari syndrome.
10. Portal vein thrombosis based on ultrasound, computed tomography (CT), or magnetic
resonance imaging (MRI) within 28 days prior to randomisation or a history of portal
vein thrombosis.
11. Absence of hepatopetal blood flow in the main trunk of the portal vein as demonstrated
by Doppler ultrasonography within 28 days prior to randomisation.
12. Untreated gastro-oesophageal varices that are bleeding or require treatment based on
upper gastrointestinal endoscopy within 180 days prior to randomisation (except for
patients in whom the primary invasive procedure is for the treatment of
gastro-oesophageal varices).
13. History or evidence of disease associated with a risk of bleeding (eg, coagulation factor
deficiency or von Willebrand factor deficiency).
14. Bleeding score at randomisation ≥ Grade 2 according to the World Health
Organization (WHO) Bleeding Scale (see Appendix 7).
15. Any of the following drugs or therapies within 90 days prior to randomisation:
anticancer drugs except for transcatheter arterial chemoembolisation (TACE) and
lipiodolisation
interferon preparations
radiation therapy
exsanguination
other TPO receptor agonist
any investigational agent.
16. Any of the following invasive procedures within 90 days prior to randomisation:
laparotomy, thoracotomy, craniotomy, or open-heart surgery
procedures involving any organ resection or any partial organ resection (tissue
resection associated with an endoscopic examination is permitted)
partial splenic embolisation.
17. Any invasive procedure (except for the treatment of gastro-oesophageal varices)
within 14 days prior to randomisation.
18. Blood transfusion (except for red blood cell products and albumin preparations) within
14 days prior to randomisation.
19. Patients who have received S-888711 before.
20. Pregnant or lactating female.
21. Patients with known or suspected ongoing, active alcohol or substance abuse. Patients
with a recent history who the investigator feels are able to comply with the study
procedures and medications will be allowed to participate.
22. Considered ineligible by the investigator for any other reason.
The Estimated Number of Participants
-
Taiwan
7 participants
-
Global
200 participants
