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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01151423




Registration number
NCT01151423
Ethics application status
Date submitted
25/06/2010
Date registered
28/06/2010

Titles & IDs
Public title
Study to Assess Efficacy and Safety of Anti-von Willebrand Factor (vWF) Nanobody in Patients With Acquired Thrombotic Thrombocytopenic Purpura (aTTP)
Scientific title
A Phase II, Single-blind, Randomized, Placebo-controlled Trial to Study the Efficacy and Safety of Anti-von Willebrand Factor Nanobody Administered as Adjunctive Treatment to Patients With Acquired Thrombotic Thrombocytopenic Purpura
Secondary ID [1] 0 0
2010-019375-30
Secondary ID [2] 0 0
ALX0681-2.1/10
Universal Trial Number (UTN)
Trial acronym
TITAN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acquired Thrombotic Thrombocytopenic Purpura 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases
Blood 0 0 0 0
Other blood disorders
Blood 0 0 0 0
Haematological diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Caplacizumab
Treatment: Other - Placebo

Experimental: Caplacizumab - Caplacizumab 10 mg once daily

Placebo comparator: Placebo - Placebo once daily


Treatment: Other: Caplacizumab
* Subjects received a first intravenous (i.v.) bolus of 10 mg (filled at 5 mg/mL) caplacizumab via push injection within 6 hours to 15 minutes prior to the first PE on study. The first PE on study could either be the very first PE session for the current episode of aTTP (if the subject was randomized prior to the initiation of PE) or the second PE session (if the subject was randomized after a single PE session).
* The first PE on study was followed by subcutaneous (s.c.) administration of 10 mg study drug within 30 minutes after the end of the PE procedure.
* All subsequent study drug administrations were daily s.c. injections within 30 minutes after the end of the PE procedure (if applicable) or within 24 hours of the previous dose.
* Subjects received caplacizumab up to 30 days after the last PE session.

Treatment: Other: Placebo
* Subjects received a first i.v. bolus of placebo via push injection within 6 hours to 15 minutes prior to the first PE on study. The first PE on study could either be the very first PE session for the current episode of aTTP (if the subject was randomized prior to the initiation of PE) or the second PE session (if the subject was randomized after a single PE session).
* The first PE on study was followed by s.c. administration of placebo within 30 minutes after the end of the PE procedure.
* All subsequent study drug administrations were daily s.c. injections within 30 minutes after the end of the PE procedure (if applicable) or within 24 hours of the previous dose.
* Subjects received placebo up to 30 days after the last PE session.
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time-to-response of Treatment Defined by a Confirmed Recovery of Platelets = 150,000/µL
Timepoint [1] 0 0
From the day of first study drug administration up to 30 days after first study drug administration
Secondary outcome [1] 0 0
Number and Percentage of Subjects With Complete Remission Following Initial Daily Plasma Exchange (PE)
Timepoint [1] 0 0
From the day of first study drug administration up to 30 days after first study drug administration
Secondary outcome [2] 0 0
Number and Percentage of Subjects With Exacerbations of TTP
Timepoint [2] 0 0
Within 30 days of last day of initial daily PE
Secondary outcome [3] 0 0
Number and Percentage of Subjects With Relapse of TTP
Timepoint [3] 0 0
Later than 30 days after the last daily PE
Secondary outcome [4] 0 0
Number of Daily PE Sessions During the Initial Daily PE Period
Timepoint [4] 0 0
During the initial daily PE period, with a median (min, max) duration of exposure to study drug of 6 (2, 36) days
Secondary outcome [5] 0 0
Total Volume of Plasma Administered During the Initial Daily PE Period
Timepoint [5] 0 0
During the initial daily PE period, with a median (min, max) duration of exposure to study drug of 6 (2, 36) days
Secondary outcome [6] 0 0
Number of Days With at Least One PE Administration During the Total Course of the Study
Timepoint [6] 0 0
During the total course of the study (from Screening till the 12-month follow-up [FU] visit)
Secondary outcome [7] 0 0
The Maximum Number of Consecutive Days Per Subject Where There Was no Interruption of PE During the Initial Daily PE Period
Timepoint [7] 0 0
During the initial daily PE period, with a median (min, max) duration of exposure to study drug of 6 (2, 36) days
Secondary outcome [8] 0 0
Resolution of Non-focal Neurological Symptoms
Timepoint [8] 0 0
From Baseline till the 12-month FU visit
Secondary outcome [9] 0 0
Number of Participants With Resolution of TTP-related Signs or Symptoms
Timepoint [9] 0 0
End of daily PE treatment period (median [min, max] duration of exposure to study drug of 6 [2, 36] days), end of study treatment period (median [min, max] duration of exposure to study drug of 36.5 [2, 90] days) and at 1 month follow-up
Secondary outcome [10] 0 0
Mortality
Timepoint [10] 0 0
From the start of the study up to 1 month follow-up
Secondary outcome [11] 0 0
Number of PE Related Adverse Events
Timepoint [11] 0 0
From the start of the study up to 1 month follow-up
Secondary outcome [12] 0 0
Number and Percentage of Subjects With PE Related AEs
Timepoint [12] 0 0
From the start of the study up to 1 month follow-up
Secondary outcome [13] 0 0
Number of Treatment-emergent Adverse Events (TEAEs) by Severity
Timepoint [13] 0 0
From the start of the study up to 1 month follow-up
Secondary outcome [14] 0 0
Number and Percentage of Subjects With TEAEs by Severity
Timepoint [14] 0 0
From the start of the study up to 1 month follow-up
Secondary outcome [15] 0 0
Number of TEAEs and Their Relationship to Study Drug
Timepoint [15] 0 0
From the start of the study up to 1 month follow-up
Secondary outcome [16] 0 0
Number of Participants Who Developed Treatment-emergent Anti-Drug Antibodies (ADA)
Timepoint [16] 0 0
From the start of the study until last follow-up visit
Secondary outcome [17] 0 0
Plasma Concentrations of Caplacizumab
Timepoint [17] 0 0
From the start of the study up to 1 month follow-up (i.e., at Baseline, Days 1 and 2 of daily PE, last day of daily PE, Day 1 after daily PE, Weeks 1, 2, 3, and 4 after daily PE, Days 3 and 7 of FU and at the 1-month FU visit).
Secondary outcome [18] 0 0
Pharmacodynamics (PD): Ristocetin Cofactor (RICO) Activity Over Time
Timepoint [18] 0 0
From the start of the study up to 1 month follow-up (i.e., at Baseline, Days 1 and 2 of daily PE, last day of daily PE, Day 1 after daily PE, Weeks 1, 2, 3, and 4 after daily PE, Days 3 and 7 of FU and at the 1-month FU visit).
Secondary outcome [19] 0 0
Pharmacodynamics: Von Willebrand Factor Antigen (vWF:Ag) Over Time
Timepoint [19] 0 0
From the start of the study drug up to 1 month follow-up (i.e., at Baseline, Days 1 and 2 of daily PE, last day of daily PE, Day 1 after daily PE, Weeks 1, 2, 3, and 4 after daily PE, Days 3 and 7 of FU and at the 1-month FU visit).
Secondary outcome [20] 0 0
PD: Coagulation Factor VIII Clotting Activity (FVIII:C) Over Time
Timepoint [20] 0 0
From the start of the study up to 1 month follow-up (i.e., at Baseline, Days 1 and 2 of daily PE, last day of daily PE, Day 1 after daily PE, Weeks 1, 2, 3, and 4 after daily PE, Days 3 and 7 of FU and at the 1-month FU visit).

Eligibility
Key inclusion criteria
* 18 years of age or older (adults) or aged 12 to < 18 years (adolescents)
* Male or female subject, willing to accept an acceptable contraceptive regimen
* Subject with a clinical diagnosis of TTP
* Requiring PE (one single PE session prior to randomization into the study was allowed)
* Subject accessible to follow-up
* Subject able to provide signed and dated informed consent and assent (if applicable, for adolescents)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Platelet count = 100,000/µL
* Severe active infection indicated by sepsis (requirement for pressors with or without positive blood cultures)
* Clinical evidence of enteric infection with Escherichia coli 0157 or related organism
* Anti-phospholipid syndrome
* Diagnosis of disseminated intravascular coagulation (DIC)
* Pregnancy or breast-feeding
* Hematopoietic stem cell or bone marrow transplantation-associated thrombotic microangiopathy
* Known with congenital TTP
* Active bleeding or high risk of bleeding
* Uncontrolled arterial hypertension
* Known chronic treatment with anticoagulant treatment that cannot be stopped safely, including but not limited to:

* vitamin K antagonists
* heparin or low molecular weight heparin (LMWH)
* non-acetyl salicylic acid non-steroidal anti-inflammatory molecules
* Severe or life threatening clinical condition other than TTP that would impair participation in the study
* Subjects with malignancies resulting in a life expectation of less than 3 months
* Subjects with known or suspected bone marrow carcinosis
* Subjects who cannot comply with study protocol requirements and procedures
* Known hypersensitivity to the active substance or to excipients of the study drug
* Severe liver impairment, corresponding to grade 3 toxicity defined by the CTCAE scale. For the key liver parameters, this is defined as follows:

* bilirubin > 3 x upper limit of normal (ULN) (needed to differentiate isolated increase in indirect bilirubin due to hemolysis, this was not an exclusion parameter but disease-related)
* alanine transaminase (ALT)/ aspartate transaminase (AST) > 5 x ULN
* alkaline phosphatase (ALP) > 5 x ULN
* gamma-glutamyl transpeptidase (GGT) > 5 x ULN
* Severe chronic renal impairment, as defined by glomerular filtration rate < 30 mL/min

Note that the use of another investigational drug or device within 30 days prior to screening was not allowed. Participation in non-interventional/observational studies and registries during the study period was allowed. Participation in another clinical study was not allowed until the end of the follow-up period or within 30 days after the last study treatment in case of early subject withdrawal from the study. Subjects who had already participated in the current study and had either completed the study per protocol or had discontinued prematurely, were not allowed to be re-included.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/01/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/03/2014
Sample size
Target
Accrual to date
Final
75
Recruitment in Australia
Recruitment state(s)
ACT
Recruitment hospital [1] 0 0
Investigator Site - Garran
Recruitment hospital [2] 0 0
Investigator Site - Liverpool
Recruitment hospital [3] 0 0
Investigator Site - Melbourne
Recruitment hospital [4] 0 0
Investigator Site - Woolloongabba
Recruitment postcode(s) [1] 0 0
- Garran
Recruitment postcode(s) [2] 0 0
- Liverpool
Recruitment postcode(s) [3] 0 0
- Melbourne
Recruitment postcode(s) [4] 0 0
- Woolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Missouri
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
North Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Utah
Country [11] 0 0
Austria
State/province [11] 0 0
Graz
Country [12] 0 0
Austria
State/province [12] 0 0
Vienna
Country [13] 0 0
Belgium
State/province [13] 0 0
Antwerp
Country [14] 0 0
Belgium
State/province [14] 0 0
Brussels
Country [15] 0 0
Belgium
State/province [15] 0 0
Leuven
Country [16] 0 0
Belgium
State/province [16] 0 0
Namur
Country [17] 0 0
Bulgaria
State/province [17] 0 0
Sofia
Country [18] 0 0
France
State/province [18] 0 0
Caen
Country [19] 0 0
Germany
State/province [19] 0 0
Baden-Wuerttemberg
Country [20] 0 0
Germany
State/province [20] 0 0
Aachen
Country [21] 0 0
Germany
State/province [21] 0 0
Berlin
Country [22] 0 0
Germany
State/province [22] 0 0
Dortmund
Country [23] 0 0
Germany
State/province [23] 0 0
Hannover
Country [24] 0 0
Germany
State/province [24] 0 0
Köln
Country [25] 0 0
Germany
State/province [25] 0 0
Mainz
Country [26] 0 0
Germany
State/province [26] 0 0
Mannheim
Country [27] 0 0
Germany
State/province [27] 0 0
Munchen
Country [28] 0 0
Israel
State/province [28] 0 0
Haifa
Country [29] 0 0
Israel
State/province [29] 0 0
Jerusalem
Country [30] 0 0
Israel
State/province [30] 0 0
Petach Tikva
Country [31] 0 0
Italy
State/province [31] 0 0
Catania
Country [32] 0 0
Italy
State/province [32] 0 0
Foggia
Country [33] 0 0
Italy
State/province [33] 0 0
Milan
Country [34] 0 0
Italy
State/province [34] 0 0
Reggio Emilia
Country [35] 0 0
Italy
State/province [35] 0 0
Rome
Country [36] 0 0
Romania
State/province [36] 0 0
Bucharest
Country [37] 0 0
Spain
State/province [37] 0 0
Badalona
Country [38] 0 0
Spain
State/province [38] 0 0
Sevilla
Country [39] 0 0
Spain
State/province [39] 0 0
Valencia
Country [40] 0 0
Switzerland
State/province [40] 0 0
Bern
Country [41] 0 0
Switzerland
State/province [41] 0 0
Lausanne
Country [42] 0 0
Switzerland
State/province [42] 0 0
Zurich
Country [43] 0 0
United Kingdom
State/province [43] 0 0
Liverpool
Country [44] 0 0
United Kingdom
State/province [44] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Ablynx, a Sanofi company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Monitor
Address 0 0
Ablynx NV
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT01151423