Phase III Trial With Caplacizumab in Patients With Acquired Thrombotic Thrombocytopenic Purpura

NCT ID: NCT02553317

Last Updated: 2023-04-05

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

145 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-11-30

Study Completion Date

2017-08-31

Brief Summary

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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

Detailed Description

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Conditions

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Acquired Thrombotic Thrombocytopenic Purpura

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Caplacizumab

Caplacizumab 10 mg once daily

Group Type EXPERIMENTAL

Caplacizumab

Intervention Type BIOLOGICAL

* 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.

Placebo

Placebo once daily

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type BIOLOGICAL

* 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.

Interventions

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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.

Intervention Type BIOLOGICAL

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 Type BIOLOGICAL

Other Intervention Names

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ALX-0081 ALX-0081 Placebo

Eligibility Criteria

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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

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ablynx, a Sanofi company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Monitor

Role: STUDY_DIRECTOR

Ablynx NV

Locations

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Investigator Site

Birmingham, Alabama, United States

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Los Angeles, California, United States

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Atlanta, Georgia, United States

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Boston, Massachusetts, United States

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St Louis, Missouri, United States

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Rochester, New York, United States

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Rochester, New York, United States

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Valhalla, New York, United States

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Chapel Hill, North Carolina, United States

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Durham, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Cleveland, Ohio, United States

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Columbus, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Pittsburgh, Pennsylvania, United States

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Charleston, South Carolina, United States

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Greenville, South Carolina, United States

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Houston, Texas, United States

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Salt Lake City, Utah, United States

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Brisbane, , Australia

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Melbourne, , Australia

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Melbourne, , Australia

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Melbourne, , Australia

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Melbourne, , Australia

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Melbourne, , Australia

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Perth, , Australia

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Sydney, , Australia

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Sydney, , Australia

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Vienna, , Austria

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Antwerp, , Belgium

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Brussels, , Belgium

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Haine-Saint-Paul, , Belgium

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La Louvière, , Belgium

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Leuven, , Belgium

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Montreal, Quebec, Canada

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London, , Canada

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Toronto, , Canada

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Brno, , Czechia

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Hradec Králové, , Czechia

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Olomouc, , Czechia

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Ostrava-Poruba, , Czechia

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Caen, , France

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Lille, , France

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Marseille, , France

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Nantes, , France

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Paris, , France

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Paris, , France

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Paris, , France

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Paris, , France

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Paris, , France

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Rouen, , France

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Salouël, , France

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Cologne, , Germany

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Dresden, , Germany

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Dresden, , Germany

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Erlangen, , Germany

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Göppingen, , Germany

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Kiel, , Germany

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Leipzig, , Germany

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Würzburg, , Germany

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Budapest, , Hungary

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Budapest, , Hungary

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Debrecen, , Hungary

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Be’er Ya‘aqov, , Israel

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Be’er Ya‘aqov, , Israel

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Haifa, , Israel

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Jerusalem, , Israel

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Jerusalem, , Israel

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Nahariya, , Israel

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Petah Tikva, , Israel

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Tel Aviv, , Israel

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Catania, , Italy

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Milan, , Italy

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Milan, , Italy

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Pesaro, , Italy

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Rome, , Italy

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Vicenza, , Italy

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Amersfoort, , Netherlands

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Leiden, , Netherlands

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Rotterdam, , Netherlands

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Veldhoven, , Netherlands

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Barcelona, , Spain

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Barcelona, , Spain

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Madrid, , Spain

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Seville, , Spain

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Valencia, , Spain

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Valencia, , Spain

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Valencia, , Spain

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Bern, , Switzerland

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Zurich, , Switzerland

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Ankara, , Turkey (Türkiye)

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Denizli, , Turkey (Türkiye)

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Denizli, , Turkey (Türkiye)

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Denizli, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Kayseri, , Turkey (Türkiye)

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Trabzon, , Turkey (Türkiye)

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Bristol, , United Kingdom

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Liverpool, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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Countries

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United States Australia Austria Belgium Canada Czechia France Germany Hungary Israel Italy Netherlands Spain Switzerland Turkey (Türkiye) United Kingdom

References

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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.

Reference Type DERIVED
PMID: 33881463 (View on PubMed)

Knoebl 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.

Reference Type DERIVED
PMID: 31691462 (View on PubMed)

Scully 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.

Reference Type DERIVED
PMID: 30625070 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2015-001098-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ALX0681-C301

Identifier Type: -

Identifier Source: org_study_id

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