A Phase III trial with caplacizumab in patients with acquired thrombotic thrombocytopenic purpura.

• Register: EUCTR
• Last refreshed on: 23 October 2017
• Main ID: EUCTR2015-001098-42-Outside-EU/EEA
• Date of registration: 16/10/2017
• Prospective Registration: Yes
• Primary sponsor: Ablynx NV
• Public title: A Phase III trial with caplacizumab in patients with acquired thrombotic thrombocytopenic purpura.
• Scientific title: A Phase III double-blind, randomized, parallel group, multicenter placebo-controlled trial to study the efficacy and safety of caplacizumab in patients with acquired thrombotic thrombocytopenic purpura. - HERCULES
• Target sample size: 132
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-001098-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: For children & adolescents open-label treatment with Caplacizumab If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Canada, Israel, Switzerland, Turkey, United States

Contacts

• Name: [e-mail]
• Affiliation: Ablynx NV

• Name: [e-mail]
• Affiliation: Ablynx NV

Key inclusion & exclusion criteria

Inclusion criteria:
1. Adult male or female = 18 years of age at the time of signing the informed consent form (ICF) or Male or female child (aged = 2 to < 12 years) or adolescent (aged = 12 to <18 years) at the time of obtaining informed consent/assent (as applicable)
2. Clinical diagnosis of acquired TTP (initial or recurrent), which includes thrombocytopenia and microscopic evidence of red blood cell fragmentation (e.g. schistocytes)
3.Requires initiation of daily PE treatment and has received PE treatment prior to randomization and prior to start of first dose of study drug for pediatric subjects.
Are the trial subjects under 18? yes
Number of subjects for this age range: 10
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 119
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 3

Exclusion criteria:
1. Platelet count =100×10E9/L
2. Serum creatinine level >200 µmol/L in case platelet count is > 30×109/L
3. Known other causes of thrombocytopenia
4. Congenital TTP (known at the time of study entry)
5. Pregnancy or breast-feeding.
6. Subjects who were previously enrolled in a clinical study with caplacizumab and received caplacizumab or for whom the assigned treatment arm is unknown.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Acquired Thrombotic thrombocytopenic purpura
MedDRA version: 20.0 Level: PT Classification code 10043648 Term: Thrombotic thrombocytopenic purpura System Organ Class: 10005329 - Blood and lymphatic system disorders

Intervention(s)

Product Name: Caplacizumab
Product Code: ALX-0081
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: Caplacizumab
CAS Number: 915810-67-2
Current Sponsor code: ALX-0081
Other descriptive name: ALX-0081
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 11.1-
Pharmaceutical form of the placebo: Powder and solvent for solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: For adults: To evaluate efficacy of caplacizumab in more rapidly restoring normal platelet counts as measure of prevention of further microvascular thrombosis.
For pediatric subjects: To explore the efficacy, safety, PK and PD properties and immunogenicity of caplacizumab in pediatric subjects experiencing an acute episode of acquired TTP

Primary end point(s): For adults only: Time to platelet count response defined as initial platelet count = 150×10E9/L with subsequent stop of daily PE within 5 days.
Data of pediatric subjects will be analyzed separately from data of adult subjects. No endpoints are defined for the pediatric subjects. Data will be analyzed descriptively.

Secondary Objective: To evaluate the effect of study drug on a composite endpoint consisting of TTP-related mortality, recurrence of TTP and major thromboembolic events during study drug treatment
- to evaluate the effect of study drug on prevention of recurrence of TTP over the entire study period
- to evaluate the effect of study drug on refractoriness to treatment
- to evaluate the effect of study drug on biomarkers of organ damage: lactate dehydrogenase (LDH), cardiac troponin I (cTnI), and serum creatinine
- to evaluate the effect of study drug on PE parameters (days of PE and volume), days in intensive care unit (ICU), days in hospital

Timepoint(s) of evaluation of this end point: daily PE period, for maximum of 6 months

Secondary Outcome(s)

Secondary end point(s): 1. Proportion of subjects with TTP-related death, a recurrence of TTP, or at least one treatment-emergent major thromboembolic event during the study drug treatment period (including extensions).
2. Proportion of subjects with a recurrence of TTP in the overall study period (including 4-week FU period).
3. Proportion of subjects with refractory TTP, defined as absence of platelet count doubling after 4 days of standard treatment, and LDH >ULN
4. Time to normalization of all 3 of the following organ damage marker
levels:
- Time to LDH = 1 x upper limit of normal (ULN), and
- Time to cTnI = 1 x ULN, and
- Time to serum creatinine = 1 x ULN

Timepoint(s) of evaluation of this end point: 1. During the treatment period (ie daily PE period + post-daily PE treatment period)
2. During the overall study period (including the FU period)
3. Will be evaluated during the daily PE period
4. During the overall study period (including the FU period)

Secondary ID(s)

ALX0681-C301

2015-001098-42-BE

NCT02553317

Source(s) of Monetary Support

Ablynx NV