A Clinical Study of Anfibatide in Acquired Thrombotic Thrombocytopenic Purpura (TTP)

A Multicenter, Randomized, Double-blind, Placebo-parallel, Phase II Clinical Trial of the Efficacy and Safety of Anfibatide in Treating Patients With Acquired Thrombotic Thrombocytopenic Purpura (TTP)

This is a multicenter, randomized, double-blind, parallel, placebo-controlled phase II clinical study. It is planned to recruit 74 patients with acquired thrombotic thrombocytopenic purpura (TTP). To evaluate the efficacy and safety of Anfibatide as an adjuvant therapy for plasma exchange in patients with acquired TTP.

Study Overview

• Status: Unknown
• Conditions: Acquired Thrombotic Thrombocytopenic Purpura
• Intervention / Treatment: Drug: Anfibatide; Drug: Placebos

Detailed Description

The study will consist of 3 periods: screening(up to 7 days), treatment and follow-up(up to 3 months). Subjects are assigned in a 1:1 ratio to Anfibatide or placebo during plasma exchange with the use of a computerized randomization schedule. The administration is 5 IU/60kg intravenous infusion and 0.002 IU/kg/h continuous intravenous infusion. Plasma exchange as the main treatment method is performed daily on the 5th day of solstice and then adjusted to every other day. Fresh frozen plasma（FFP）and cryoprecipitate-reduced plasma are preferred. Subjects will receive the study drug immediately after daily plasma exchange.

• Study Type: Interventional
• Enrollment (Anticipated): 74
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Weili Zhao, MD; Phone Number: 13512112076; Email: zhaoweili-sih@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Shanghai Ruijing Hospital
      • Contact: Weili Zhao, MD; Phone Number: 13512112076; Email: zhaoweili-sih@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Female and male subjects with 18 years of age or older.
2. Subjects with diagnosis of TTP.
3. Necessitating plasma exchange.
4. Obtained, signed and dated informed consent.

Exclusion Criteria:

1. Platelet count greater or equal to 100*10^9/μL.
2. Severe heart, liver and kidney dysfunction, including those with glutamic-pyruvic transaminase ≥ 5xULN，glomerular filtration rate <30ml/min.
3. Uncontrolled severe active infection.
4. Known congenital TTP.
5. Subjects with malignant tumors in the past 5 years.
6. Other diseases that cause microangiopathy hemolytic anemia and thrombocytopenia, such as disseminated intravascular coagulation (DIC), antiphospholipid antibody syndrome, hemolytic uremic syndrome, malignant hypertension, and transplant-related microangiopathy.
7. Pregnant or lactating women. Subjects of reproductive age, are unable to use effective contraceptive methods during the study period.
8. Severe active bleeding or progressive aggravation of bleeding symptoms.
9. Subjects who have received plasmapheresis during the treatment of the onset of the disease.
10. Subject is participating in other clinical stuy or is less than 3 months away from the end of previous clinical study.
11. Subject who have participated in other clinical trials related to Anfibatide.
12. Severe or life threatening clinical condition other than TTP that would impair participation in the trial.
13. Life expectation less than 1 week.
14. Known to be allergic to the drugs or ingredients in the study.
15. Inability to follow programme requirements and procedures.
16. Subjects who are not eligible to participate in this clinical study as determined by the investigator.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebos; 5 IU/60kg intravenous infusion follow by 0.002 IU/kg/h continuous intravenous infusion
Experimental: Anfibatide	Drug: Anfibatide; 5 IU/60kg intravenous infusion follow by 0.002 IU/kg/h continuous intravenous infusion; Other Names: Anti-platelet thrombolysin for injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to response of treatment	Time to response of treatment ,defined by a recovery of platelets ≥100*10^9/l	up to 21days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Remission rate	Number of subjects with remission	up to 21days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete remission rate	Number of subjects with complete remission	up to 21 days
Number of plasma exchange	The number of plasma exchange to achieved remission.	up to 21 days
Volume of plasma	The volume of plasma to achieved remission.	up to 21 days
Time to achieve threshold values of biological markers.	The biological markers include platelets，LDH and creatinine.	up to 3 months
Total mortality	Total mortality within the plasma exchange treatment period and the ensuing 30 days.	up to 21days and the ensuing 30 days
Number of exacerbations of TTP and time to first exacerbation of TTP.	Exacerbation is defined as recurrent thrombocytopenia following a response and requiring a reinitiation of daily plasma exchange treatment after ≥ 1 day but ≤ 30 days of no plasma exchange treatment.	up to 1 month
Number of subjects relapsing of TTP for maximum of 3 months and time to first relapse of TTP.	Relapse is defined as novo event of TTP that occurs later than 30 days after the last plasma exchange.	up to 3 months

Collaborators and Investigators

• Sponsor: Lee's Pharmaceutical Limited
• Investigators: Study Director: Weili Zhao, MD, Shanghai Ruijing Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2019
• Primary Completion (Anticipated): July 1, 2021
• Study Completion (Anticipated): November 1, 2021

Study Registration Dates

• First Submitted: July 15, 2019
• First Submitted That Met QC Criteria: July 15, 2019
• First Posted (Actual): July 16, 2019

Study Record Updates

• Last Update Posted (Actual): July 17, 2019
• Last Update Submitted That Met QC Criteria: July 15, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Hematologic Diseases; Hemorrhage; Blood Coagulation Disorders; Skin Manifestations; Thrombocytopenia; Blood Platelet Disorders; Thrombophilia; Thrombotic Microangiopathies; Purpura; Purpura, Thrombocytopenic; Purpura, Thrombotic Thrombocytopenic; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Fibrinolysin
• Other Study ID Numbers: APT-ZK-201901

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