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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02553317




Registration number
NCT02553317
Ethics application status
Date submitted
14/09/2015
Date registered
17/09/2015
Date last updated
22/05/2019

Titles & IDs
Public title
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
Secondary ID [1] 0 0
2015-001098-42
Secondary ID [2] 0 0
ALX0681-C301
Universal Trial Number (UTN)
Trial acronym
HERCULES
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
Other interventions - Caplacizumab
Other interventions - Placebo

Experimental: Caplacizumab - Caplacizumab 10 mg once daily

Placebo Comparator: Placebo - Placebo once daily


Other interventions: Caplacizumab
First day of treatment: 10 mg intravenous (i.v.) injection prior to plasma exchange (PE) followed by a 10 mg subcutaneous (s.c.) injection (in the abdominal region) after completion of PE on that day.
Subsequent days of treatment during PE: daily 10 mg s.c. injection (in the abdominal region) following PE.
Treatment after PE period: daily 10 mg s.c. injections for 30 days. If the underlying immunological disease was not resolved, treatment could be extended for a maximum of 4 additional 1-week periods (i.e., 28 days) and was to be accompanied by optimization of immunosuppression.

Other interventions: Placebo
First day of treatment: i.v. injection prior to PE followed by a s.c. injection (in the abdominal region) after completion of PE on that day.
Subsequent days of treatment during PE: daily s.c. injection (in the abdominal region) following PE.
Treatment after PE period: daily s.c. injections for 30 days. If the underlying immunological disease was not resolved, treatment could be extended for a maximum of 4 additional 1-week periods (i.e., 28 days) and was to be accompanied by optimization of immunosuppression.

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to Platelet Count Response - Platelet count response was defined as initial platelet count = 150,000/µL with subsequent stop of daily PE within 5 days. It refers to the first time both conditions, platelet count = 150,000/µL and the stop of daily PE within 5 days, were met.
Timepoint [1] 0 0
Only data from the DB daily PE period (median = 5 days) up to the cut-off were used. The cut-off point was defined by whichever occured first: 1) 45 days of daily PE after start of study drug, 2) stop of daily PE, 3) stop of study drug (median = 34 days)
Secondary outcome [1] 0 0
Number and Percentage of Subjects With TTP-Related Death, Recurrence of TTP, or a Major Thromboembolic Event During the Study Drug Treatment Period - Number and percentage 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 (i.e., first key secondary endpoint).
Timepoint [1] 0 0
The study drug treatment period, a median (min, max) of 36 (2, 82) days. For both treatment groups, only events that occurred prior to a switch to open-label caplacizumab were evaluated for this analysis.
Secondary outcome [2] 0 0
Number and Percentage of Subjects With a Recurrence of TTP in the Overall Study Period - Number and percentage of subjects with a recurrence of TTP during the Overall Study Period (i.e., including follow-up [FU]) (i.e., second key secondary endpoint).
Timepoint [2] 0 0
The overall study period (covers both the overall treatment period and the follow-up period), a median (min, max) of 65 (2, 110) days.
Secondary outcome [3] 0 0
Number and Percentage of Subjects With Refractory Disease - Number and percentage of subjects with refractory TTP, defined as absence of platelet count doubling after 4 days of standard treatment, and lactate dehydrogenase (LDH) > upper limit of normal (ULN) (i.e., third key secondary endpoint).
Timepoint [3] 0 0
The study drug treatment period, a median (min, max) of 36 (2, 82) days.
Secondary outcome [4] 0 0
Time to Normalization of Organ Damage Marker Levels - Time to first normalization of LDH, cardiac troponin I (cTnI) and serum creatinine was defined as: first time of LDH = ULN and cTnI = ULN and serum creatinine = ULN - time of first i.v. loading dose of study drug after randomization + 1 minute. Subjects in either initial treatment group who switched to open-label caplacizumab before having reached the endpoint were censored at time of switch.
Of note, the key secondary endpoints were hierarchically ordered to allow statistical testing for these endpoints at the same nominal significance level of 5% without adjustment, as long as the tests occurred in the pre-defined sequential order, and given that all null hypotheses tested for endpoints with a higher rank (including the primary endpoint) were rejected. No confirmatory testing was done for this fourth key secondary endpoint, as the statistical test was not significant for the proportion of subjects with refractory disease (i.e., the third key secondary endpoint).
Timepoint [4] 0 0
Overall study period, a median (min, max) of 65 (2, 110) days. For both treatment groups, normalizations occurring during the open-label period were not evaluated in this analysis.

Eligibility
Key inclusion criteria
1. Adult male or female = 18 years of age at the time of signing the informed consent
form (ICF).

2. Clinical diagnosis of acquired thrombotic thrombocytopenic purpura (aTTP) (initial or
recurrent), which included thrombocytopenia and microscopic evidence of red blood cell
fragmentation (e.g., schistocytes).

3. Required initiation of daily PE treatment and had received 1 PE treatment prior to
randomization

4. Others as defined in the protocol
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Platelet count =100×10E9/L.

2. Serum creatinine level >200 µmol/L in case platelet count is > 30×10E9/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

7. Others as defined in the protocol

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
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Investigator Site - Brisbane
Recruitment hospital [2] 0 0
Investigator Site 1 - Melbourne
Recruitment hospital [3] 0 0
Investigator Site 2 - Melbourne
Recruitment hospital [4] 0 0
Investigator Site 3 - Melbourne
Recruitment hospital [5] 0 0
Investigator Site 4 - Melbourne
Recruitment hospital [6] 0 0
Investigator Site 5 - Melbourne
Recruitment hospital [7] 0 0
Investigator Site - Perth
Recruitment hospital [8] 0 0
Investigator Site 1 - Sydney
Recruitment hospital [9] 0 0
Investigator Site 2 - Sydney
Recruitment postcode(s) [1] 0 0
- Brisbane
Recruitment postcode(s) [2] 0 0
- Melbourne
Recruitment postcode(s) [3] 0 0
- Perth
Recruitment postcode(s) [4] 0 0
- Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
State/province [2] 0 0
California
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United States of America
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Georgia
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Massachusetts
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Missouri
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New York
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North Carolina
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United States of America
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Ohio
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United States of America
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Oklahoma
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United States of America
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Pennsylvania
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South Carolina
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United States of America
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Texas
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United States of America
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Utah
Country [14] 0 0
Austria
State/province [14] 0 0
Vienna
Country [15] 0 0
Belgium
State/province [15] 0 0
Antwerp
Country [16] 0 0
Belgium
State/province [16] 0 0
Brussels
Country [17] 0 0
Belgium
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Haine-Saint-Paul
Country [18] 0 0
Belgium
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La Louviere
Country [19] 0 0
Belgium
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Leuven
Country [20] 0 0
Canada
State/province [20] 0 0
Quebec
Country [21] 0 0
Canada
State/province [21] 0 0
London
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Canada
State/province [22] 0 0
Toronto
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Czechia
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Brno
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Czechia
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Hradec Kralove
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Czechia
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Olomouc
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Czechia
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Ostrava-Poruba
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France
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Caen
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France
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Lille
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France
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Marseille
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France
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Nantes
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France
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Paris
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France
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Rouen
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France
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Salouel
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Germany
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Dresden
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Germany
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Erlangen
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Germany
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Goppingen
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Germany
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Kiel
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Germany
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Köln
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Germany
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Leipzig
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Germany
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Würzburg
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Hungary
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Budapest
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Hungary
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Debrecen
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Israel
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Be'er Ya'aqov
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Israel
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Be'er Ya`aqov
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Israel
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Haifa
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Israel
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Jerusalem
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Israel
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Nahariya
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Israel
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Petah Tiqva
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Israel
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Tel Aviv
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Italy
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Catania
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Italy
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Milan
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Italy
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Pesaro
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Italy
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Rome
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Italy
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Vicenza
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Netherlands
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Amersfoort
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Netherlands
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Leiden
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Rotterdam
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Netherlands
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Veldhoven
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Spain
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Barcelona
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Madrid
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Sevilla
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Spain
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Valencia
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Switzerland
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Bern
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Switzerland
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Zurich
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Turkey
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Ankara
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Turkey
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Denizli
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Turkey
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Istanbul
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Turkey
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Kayseri
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Turkey
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Trabzon
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United Kingdom
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Bristol
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United Kingdom
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Liverpool
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United Kingdom
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London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Ablynx
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The study was a Phase III, double-blind, placebo-controlled, randomized study to evaluate the
efficacy of caplacizumab in more rapidly restoring normal platelet counts as measure of
prevention of further microvascular thrombosis
Trial website
https://clinicaltrials.gov/show/NCT02553317
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

Summary results
Other publications