Eltrombopag Phase III Study In Chinese Chronic ITP Patients

NCT01762761 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: 113765CETB115B2301
• Study Type: interventional
• Target: 155
• Locations: 1 country
• Sites: 18

Brief Summary

This randomized, double-blind and open-label phase III study aimed to determine the efficacy, tolerance and safety of eltrombopag in Chinese chronic primary immune thrombocytopenia (ITP) adult subjects. This study was be conducted in Chinese adult chronic ITP subjects who had not responded to or had relapsed after previous treatment of ITP, including first line therapy and /or splenectomy. The primary objective of this study was to determine the efficacy of oral eltrombopag as a thrombopoietic agent treating previously treated chronic Chinese ITP patients compared to placebo. The secondary objective was to assess the safety and tolerability of eltrombopag when administered for 6 weeks to previously treated adult chronic ITP patients compared with placebo. In addition, the long-term efficacy and safety of eltrombopag treatment was also evaluated in the 24-week extension open-label phase after the double-blind phase as one of other study objectives. If the subject benefited from the eltrombopag treatment based on the investigator's discretion, the subject could continue on eltrombopag treatment until the commercial launch of eltrombopag in China. Furthermore, to understand the pharmacokinetics (PK) profile of eltrombopag and to explore the relationship between the PK and pharmacodynamics (PD) (platelet response), a PK/PD analysis was embedded in this phase III study and conducted in the same patient population who participated this phase III study.

Conditions

Purpura, Thrombocytopenic, Idiopathic and Hepatitis C

Keywords

eltrombopag; TPO-R agonist; Chronic ITP; ETB115; Chinese chronic ITP patients

Outcome Measures

Primary Outcomes (1)

• Number of Participants (Responders) Achieving a Platelet Count >=50×10^9/L After the First 6 Weeks of Stage 1

  The number of participants (responders) with platelet count \>=50x10\^9/L after 6 weeks of Stage 1 were compared between treatments using a logistic regression model adjusted for use of primary immune thrombocytopenia (ITP) medication at Baseline (yes/no), splenectomy (yes/no), Baseline platelet count \<=15×10\^9/L (yes/no) and treatment. Complete blood count including platelet count was done at Week 1, Week 2, Week 3, Week 4, Week 5 and Week 6. Primary Analysis Data Set: a participant who withdrawals from Stage 1 or is emergently unblinded was classified as a negative response from the time of withdrawal or unblinding date and for all subsequent visits. In the event of a participant dying, information for all subsequent assessments would be considered missing. All intermittent missing data (apart from withdrawals) will be treated as missing.

  From the start of study treatment (Day 1) up to the end of Week 6 of Stage 1

Secondary Outcomes (29)

• Number of Participants Achieving a Platelet Count >=50×10^9/L at Least Once During the First 6 Weeks of Stage 1

  From the start of study treatment (Day 1) up to the end of Week 6 of Stage 1

• Number of Participants Achieving a Platelet Count >=30×10^9/L and at Least 2 Times the Baseline Platelet Count at Least Once During the 6 Weeks of Stage 1, the Whole Stage 2 and the Whole Stage 3

  From the start of study treatment (Day 1) up to the end of Stage 3

• Number of Participants With Bleeding as Assessed Using the World Health Organization (WHO) Bleeding Scale

  From the start of study treatment (Day 1) up to the end of Stage 3

• Number of Participants With Clinically Significant Bleeding as Assessed Using the World Health Organization (WHO) Bleeding Scale

  From the start of study treatment (Day 1) up to the end of Stage 3

• Time to Response

  From the start of study treatment (Day 1) up to the end of Week 6 of Stage 1

Study Arms (2)

Eltrombopag (ETB115)

EXPERIMENTAL

Thrombopoietin- receptor (TPO-R) agonist

Drug: eltrombopag

Placebo

PLACEBO COMPARATOR

Placebo

Drug: placebo

Interventions

eltrombopag DRUG

TPO-R agonist

Also known as: ETB115

Eltrombopag (ETB115)

placebo DRUG

placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is ≥18 years old.
• Diagnosed with ITP for at least 12 months prior to screening, and have a platelet count of \<30 X109/L on Day 1 (or within 48 hours prior to dosing on Day 1).
• Patients who have no response or relapsed after splenectomy. Or patients who have not been splenectomised and have either not responded to one or more prior therapies (except splenectomy), or who have relapsed prior therapy.
• Previous therapy for ITP including rescue must have been completed at least 2 weeks prior to randomization.
• Subjects treated with maintenance immunosuppressive therapy must be receiving a dose that has been stable for at least 1 month.
• No pre-existing cardiac disease within the last 3 months. No arrhythmia known to increase the risk of thrombolic events (e.g. atrial fibrillation), or patients with a Corrected QT interval (QTc) \>450msec or QTc \>480 for patients with a Bundle Branch Block.
• No history of clotting disorder, other than ITP.
• A complete blood count (CBC), within the reference range, with the following exceptions:
• Blood chemistry test result no exceed normal by more than 20%. Total albumin must not be below the lower limit of normal (LLN) by more than 10%.
• Subject is non-childbearing potential of childbearing potential and use acceptable methods of contraception from two weeks prior to administration of study medication, throughout the study, and 28 days after completion or premature discontinuation from the study.

You may not qualify if:

• Patients with any prior history of arterial or venous thrombosis, AND ≥ two of the following risk factors: hormone replacement therapy, systemic contraception (containing estrogen), smoking, diabetes, hypercholesterolemia, medication for hypertension, cancer, hereditary thrombophilic disorders (e.g., Factor V Leiden, ATIII deficiency, antiphospholipid syndrome, etc).
• Any clinically relevant abnormality, other than ITP,which in the opinion of the investigator makes the subject unsuitable for participation in the study.
• Female subjects who are nursing or pregnant at screening or pre-dose on Day 1.
• History of alcohol/drug abuse or dependence within 12 months of the study.
• Treatment with thrombopoietin or an investigational drug within 30 days or five half-lives (whichever is longer) preceding the first dose of study medication.
• Subjects who have previously received eltrombopag or any other thrombopoietin receptor agonist.
• Subject has consumed aspirin, aspirin-containing compounds, salicylates, anticoagulants, quinine or non-steroidal anti-inflammatories (NSAIDs) for \>3 consecutive days within 2 weeks of the study start and until the end of the study.
• Consumption of any herbal or dietary supplements, excluding vitamin or mineral supplements, within 1 week of the study start.
• History of platelet aggregation that prevents reliable measurement of platelet counts.
• An abnormality in bone marrow examination result, other than ITP, identified on the screening examination, which in the opinion of the investigator makes the subject unsuitable for participation in the study (e.g. ≥MF-2 according to EU consensus scale \[Thiele, 2005\]) or suggests another primary diagnosis (e.g. Thrombocytopenia is secondary to another disease).
• Any laboratory or clinical evidence for HIV infection.
• Any clinical history for hepatitis C infection; chronic hepatitis B infection; or any evidence for active hepatitis at the time of subject screening. Laboratory test shows positive serology for Hepatitis C or Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test will be performed and if positive the subject will be excluded.
• Patients expected to require rescue on Day 1 of the study.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (18)

Novartis Investigative Site

Fuzhou, Fujian, 350001, China

Location

Novartis Investigative Site

Guangzhou, Guangdong, 510080, China

Location

Novartis Investigative Site

Guangzhou, Guangdong, 510515, China

Location

Novartis Investigative Site

Zhongshan, Guangdong, 528403, China

Location

Novartis Investigative Site

Changsha, Hunan, 410013, China

Location

Novartis Investigative Site

Nanjing, Jiangsu, 210029, China

Location

Novartis Investigative Site

Suzhou, Jiangsu, 215006, China

Location

Novartis Investigative Site

Nanchang, Jiangxi, 330006, China

Location

Novartis Investigative Site

Jianan, Shandong, 250012, China

Location

Novartis Investigative Site

Hangzhou, Zhejiang, 310003, China

Location

Novartis Investigative Site

Beijing, 100034, China

Location

Novartis Investigative Site

Beijing, 100044, China

Location

Novartis Investigative Site

Beijing, 100083, China

Location

Novartis Investigative Site

Beijing, 100730, China

Location

Novartis Investigative Site

Chengdu, 610041, China

Location

Novartis Investigative Site

Shanghai, 200025, China

Location

Novartis Investigative Site

Shanghai, China

Location

Novartis Investigative Site

Tianjin, 300020, China

Location

Related Publications (1)

• Liu X, Hou M, Li J, Jin J, Huang M, Yu Z, Xu X, Zhang X, Yang R. Efficacy and safety of eltrombopag in Chinese patients with chronic immune thrombocytopenia: stage 2 results from a multicenter phase III study. Platelets. 2022 Jan 2;33(1):82-88. doi: 10.1080/09537104.2020.1847267. Epub 2020 Nov 29.

  PMID: 33251910 DERIVED

MeSH Terms

Conditions

Purpura; Hepatitis C

Interventions

eltrombopag

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Clinical Disclosure Office
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2012
• First Posted: January 8, 2013
• Study Start: February 18, 2013
• Primary Completion: June 5, 2014
• Study Completion: November 22, 2018
• Last Updated: December 3, 2019
• Results First Posted: March 9, 2015

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will share

Locations

CN (18)