Phase III Trial With Caplacizumab in Patients With Acquired Thrombotic Thrombocytopenic Purpura
HERCULES
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
2 other identifiers
interventional
145
15 countries
100
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 Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Nov 2015
100 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 14, 2015
CompletedFirst Posted
Study publicly available on registry
September 17, 2015
CompletedStudy Start
First participant enrolled
November 1, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
August 1, 2017
CompletedResults Posted
Study results publicly available
May 22, 2019
CompletedApril 5, 2023
May 1, 2019
1.8 years
September 14, 2015
February 25, 2019
March 31, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
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.
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 Outcomes (4)
Number and Percentage of Subjects With TTP-Related Death, Recurrence of TTP, or a Major Thromboembolic Event During the Study Drug Treatment Period
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.
Number and Percentage of Subjects With a Recurrence of TTP in the Overall Study Period
The overall study period (covers both the overall treatment period and the follow-up period), a median (min, max) of 65 (2, 110) days.
Number and Percentage of Subjects With Refractory Disease
The study drug treatment period, a median (min, max) of 36 (2, 82) days.
Time to Normalization of Organ Damage Marker Levels
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.
Other Outcomes (4)
Number of Days of Plasma Exchange
Overall study drug treatment period, a median (min, max) of 36 (2, 82) days.
Total Volume of Plasma Exchange
Overall study drug treatment period, a median (min, max) of 36 (2, 82) days.
Number of Days in Intensive Care Unit
Overall study drug treatment period, a median (min, max) of 36 (2, 82) days.
- +1 more other outcomes
Study Arms (2)
Caplacizumab
EXPERIMENTALCaplacizumab 10 mg once daily
Placebo
PLACEBO COMPARATORPlacebo once daily
Interventions
* 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.
* 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.
Eligibility Criteria
You may qualify if:
- Adult male or female ≥ 18 years of age at the time of signing the informed consent form (ICF).
- 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).
- Required initiation of daily PE treatment and had received 1 PE treatment prior to randomization
- Others as defined in the protocol
You may not qualify if:
- Platelet count ≥100×10E9/L.
- Serum creatinine level \>200 µmol/L in case platelet count is \> 30×10E9/L
- Known other causes of thrombocytopenia
- Congenital TTP (known at the time of study entry).
- Pregnancy or breast-feeding.
- Subjects who were previously enrolled in a clinical study with caplacizumab and received caplacizumab or for whom the assigned treatment arm is unknown
- Others as defined in the protocol
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (101)
Investigator Site
Birmingham, Alabama, 35249, United States
Investigator Site
Los Angeles, California, 90033, United States
Investigator Site
Atlanta, Georgia, 30322, United States
Investigator Site
Boston, Massachusetts, 02114, United States
Investigator Site
St Louis, Missouri, 63110, United States
Investigator Site
Rochester, New York, 14642, United States
Investigator Site
Rochester, New York, 55905, United States
Investigator Site
Valhalla, New York, 10595, United States
Investigator Site
Chapel Hill, North Carolina, 27599, United States
Investigator Site
Durham, North Carolina, 27710, United States
Investigator Site
Winston-Salem, North Carolina, 27157, United States
Investigator SIte
Cleveland, Ohio, 44195, United States
Investigator Site
Columbus, Ohio, 43210, United States
Investigator Site
Oklahoma City, Oklahoma, 73104, United States
Investigator Site
Pittsburgh, Pennsylvania, 15213, United States
Investigator Site
Charleston, South Carolina, 29425, United States
Investigator Site
Greenville, South Carolina, 27834, United States
Investigator Site
Houston, Texas, 77030, United States
Investigator Site
Salt Lake City, Utah, 84112, United States
Investigator Site
Brisbane, Australia
Investigator Site 1
Melbourne, Australia
Investigator Site 2
Melbourne, Australia
Investigator Site 3
Melbourne, Australia
Investigator Site 4
Melbourne, Australia
Investigator Site 5
Melbourne, Australia
Investigator Site
Perth, Australia
Investigator Site 1
Sydney, Australia
Investigator Site 2
Sydney, Australia
Investigator Site
Vienna, Austria
Investigator Site
Antwerp, Belgium
Investigator Site
Brussels, Belgium
Investigator Site
Haine-Saint-Paul, Belgium
Investigator Site
La Louvière, Belgium
Investigator Site
Leuven, Belgium
Invesigator Site
Montreal, Quebec, Canada
Investigator Site
London, Canada
Investigator Site
Toronto, Canada
Investigator Site
Brno, Czechia
Investigator Site
Hradec Králové, Czechia
Investigator Site
Olomouc, Czechia
Investigator Site
Ostrava-Poruba, Czechia
Investigator Site
Caen, France
Investigator Site
Lille, France
Investigator Site
Marseille, France
Investigator Site
Nantes, France
Investigator Site 1
Paris, France
Investigator Site 2
Paris, France
Investigator Site 3
Paris, France
Investigator Site 4
Paris, France
Investigator site 5
Paris, France
Investigator Site
Rouen, France
Investigator Site
Salouël, France
Investigator site
Cologne, Germany
Investigator site 1
Dresden, Germany
Investigator site 2
Dresden, Germany
Investigator site
Erlangen, Germany
Investigator site
Göppingen, Germany
Investigator site
Kiel, Germany
Investigator site
Leipzig, Germany
Investigator site
Würzburg, Germany
Investigator Site 1
Budapest, Hungary
Investigator Site 2
Budapest, Hungary
Investigator Site
Debrecen, Hungary
Investigator Site 1
Be’er Ya‘aqov, Israel
Investigator Site 2
Be’er Ya‘aqov, Israel
Investigator Site
Haifa, Israel
Investigator Site 1
Jerusalem, Israel
Investigator Site 2
Jerusalem, Israel
Investigator Site
Nahariya, Israel
Investigator Site
Petah Tikva, Israel
Investigator Site
Tel Aviv, Israel
Investigator Site
Catania, Italy
Investigator Site 1
Milan, Italy
Investigator Site 2
Milan, Italy
Investigator Site
Pesaro, Italy
Investigator Site
Rome, Italy
Investigator Site
Vicenza, Italy
Investigator Site
Amersfoort, Netherlands
Investigator Site
Leiden, Netherlands
Investigator Site
Rotterdam, Netherlands
Investigator Site
Veldhoven, Netherlands
Investigator Site 1
Barcelona, Spain
Investigator Site 2
Barcelona, Spain
Investigator Site
Madrid, Spain
Investigator Site
Seville, Spain
Investigator Site 1
Valencia, Spain
Investigator Site 2
Valencia, Spain
Investigator site 3
Valencia, Spain
Investigator Site
Bern, Switzerland
Investigator Site
Zurich, Switzerland
Investigator Site
Ankara, Turkey (Türkiye)
Investigator Site 1
Denizli, Turkey (Türkiye)
Investigator Site 2
Denizli, Turkey (Türkiye)
Investigator site 3
Denizli, Turkey (Türkiye)
Investigator Site
Istanbul, Turkey (Türkiye)
Investigator Site
Kayseri, Turkey (Türkiye)
Investigator Site
Trabzon, Turkey (Türkiye)
Investigator Site
Bristol, United Kingdom
Investigator Site
Liverpool, United Kingdom
Investigator Site 1
London, United Kingdom
Investigator Site 2
London, United Kingdom
Related Publications (3)
Peyvandi F, Cataland S, Scully M, Coppo P, Knoebl P, Kremer Hovinga JA, Metjian A, de la Rubia J, Pavenski K, Minkue Mi Edou J, De Winter H, Callewaert F. Caplacizumab prevents refractoriness and mortality in acquired thrombotic thrombocytopenic purpura: integrated analysis. Blood Adv. 2021 Apr 27;5(8):2137-2141. doi: 10.1182/bloodadvances.2020001834.
PMID: 33881463DERIVEDKnoebl P, Cataland S, Peyvandi F, Coppo P, Scully M, Kremer Hovinga JA, Metjian A, de la Rubia J, Pavenski K, Minkue Mi Edou J, De Winter H, Callewaert F. Efficacy and safety of open-label caplacizumab in patients with exacerbations of acquired thrombotic thrombocytopenic purpura in the HERCULES study. J Thromb Haemost. 2020 Feb;18(2):479-484. doi: 10.1111/jth.14679. Epub 2019 Dec 9.
PMID: 31691462DERIVEDScully M, Cataland SR, Peyvandi F, Coppo P, Knobl P, Kremer Hovinga JA, Metjian A, de la Rubia J, Pavenski K, Callewaert F, Biswas D, De Winter H, Zeldin RK; HERCULES Investigators. Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura. N Engl J Med. 2019 Jan 24;380(4):335-346. doi: 10.1056/NEJMoa1806311. Epub 2019 Jan 9.
PMID: 30625070DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Monitor
- Organization
- Ablynx
Study Officials
- STUDY DIRECTOR
Medical Monitor
Ablynx NV
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
September 14, 2015
First Posted
September 17, 2015
Study Start
November 1, 2015
Primary Completion
August 1, 2017
Study Completion
August 1, 2017
Last Updated
April 5, 2023
Results First Posted
May 22, 2019
Record last verified: 2019-05
Data Sharing
- IPD Sharing
- Will share
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