Study to Assess Efficacy and Safety of Anti-von Willebrand Factor (vWF) Nanobody in Patients With Acquired Thrombotic Thrombocytopenic Purpura (aTTP)

NCT01151423 | Completed Phase 2 Results DMC

• 2 other identifiers: ALX0681-2.1/102010-019375-30
• Study Type: interventional
• Target: 75
• Locations: 12 countries
• Sites: 49

Brief Summary

This study was a Phase II, single-blind, randomized, placebo-controlled trial to determine whether anti-vWF Nanobody is safe and effective as adjunctive treatment in patients with aTTP. Patients received either placebo or anti-vWF Nanobody as adjunctive therapy to plasma exchange (PE).

Conditions

Acquired Thrombotic Thrombocytopenic Purpura

Outcome Measures

Primary Outcomes (1)

• Time-to-response of Treatment Defined by a Confirmed Recovery of Platelets ≥ 150,000/µL

  Time-to-response, defined by the achievement of platelet count response, confirmed at 48 hours after the initial reporting of this response. Platelet response was defined as recovery of platelets ≥ 150,000/µL. This response had to be confirmed at 48 hours after the initial reporting of platelet recovery ≥ 150,000/µL by a de novo measure of platelets ≥ 150,000/µL and lactate dehydrogenase (LDH) ≤ 2x upper limit of normal (ULN) (i.e., 'confirmed platelet response').

  From the day of first study drug administration up to 30 days after first study drug administration

Secondary Outcomes (20)

• Number and Percentage of Subjects With Complete Remission Following Initial Daily Plasma Exchange (PE)

  From the day of first study drug administration up to 30 days after first study drug administration

• Number and Percentage of Subjects With Exacerbations of TTP

  Within 30 days of last day of initial daily PE

• Number and Percentage of Subjects With Relapse of TTP

  Later than 30 days after the last daily PE

• Number of Daily PE Sessions During the Initial Daily PE Period

  During the initial daily PE period, with a median (min, max) duration of exposure to study drug of 6 (2, 36) days

• Total Volume of Plasma Administered During the Initial Daily PE Period

  During the initial daily PE period, with a median (min, max) duration of exposure to study drug of 6 (2, 36) days

Study Arms (2)

Caplacizumab

EXPERIMENTAL

Caplacizumab 10 mg once daily

Biological: Caplacizumab

Placebo

PLACEBO COMPARATOR

Placebo once daily

Biological: Placebo

Interventions

Caplacizumab BIOLOGICAL

* 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.

Also known as: anti-vWF Nanobody, ALX-0081

Caplacizumab

Placebo BIOLOGICAL

* 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.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Ablynx, a Sanofi company: lead

Study Sites (51)

Investigator Site

Los Angeles, California, 90033, United States

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Washington D.C., District of Columbia, United States

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Atlanta, Georgia, 30322, United States

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St Louis, Missouri, 63110, United States

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New York, New York, 10021, United States

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Rochester, New York, 14642, United States

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Valhalla, New York, 10595, United States

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Durham, North Carolina, 27710, United States

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Winston-Salem, North Carolina, 27157, United States

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Columbus, Ohio, 43210, United States

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Pittsburgh, Pennsylvania, 15224, United States

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Dallas, Texas, United States

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Salt Lake City, Utah, 84132, United States

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Garran, Australian Capital Territory, Australia

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Liverpool, Australia

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Melbourne, Australia

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Woolloongabba, Australia

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Graz, Austria

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Vienna, Austria

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Antwerp, Belgium

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Brussels, Belgium

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Leuven, Belgium

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Namur, Belgium

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Sofia, Bulgaria

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Caen, France

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Ulm, Baden-Wurttemberg, Germany

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Aachen, Germany

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Berlin, Germany

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Cologne, Germany

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Dortmund, Germany

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Hanover, Germany

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Mainz, Germany

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Mannheim, Germany

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München, Germany

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Haifa, Israel

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Jerusalem, Israel

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Petah Tikva, Israel

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Catania, Italy

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Foggia, Italy

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Milan, Italy

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Reggio Emilia, Italy

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Rome, Italy

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Bucharest, Romania

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Badalona, Spain

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Seville, Spain

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Valencia, Spain

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Bern, Switzerland

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Lausanne, Switzerland

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Zurich, Switzerland

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Liverpool, United Kingdom

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London, United Kingdom

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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: 33881463 DERIVED

• Peyvandi F, Scully M, Kremer Hovinga JA, Cataland S, Knobl P, Wu H, Artoni A, Westwood JP, Mansouri Taleghani M, Jilma B, Callewaert F, Ulrichts H, Duby C, Tersago D; TITAN Investigators. Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura. N Engl J Med. 2016 Feb 11;374(6):511-22. doi: 10.1056/NEJMoa1505533.

  PMID: 26863353 DERIVED

• Holz JB. The TITAN trial--assessing the efficacy and safety of an anti-von Willebrand factor Nanobody in patients with acquired thrombotic thrombocytopenic purpura. Transfus Apher Sci. 2012 Jun;46(3):343-6. doi: 10.1016/j.transci.2012.03.027. Epub 2012 Apr 3.

  PMID: 22475545 DERIVED

MeSH Terms

Conditions

Purpura, Thrombotic Thrombocytopenic

Interventions

caplacizumab

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Thrombophilia; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Limitations and Caveats

The study was stopped prematurely before meeting its enrollment target. The study is not considered to have been terminated as sites were requested to perform the assessments until 1-month follow-up if they had subjects in the study.

Results Point of Contact

• Title: Medical Monitor
• Organization: Ablynx

clinicaltrials@ablynx.com

+32 (9) 262 00 00

Study Officials

• Medical Monitor

  Ablynx NV

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: A single-blinded study design was initiated because, in the initial versions of the protocol, the dosing regimen could be adjusted dependent on the results of the Ristocetin Cofactor (RICO) test following the initial dose. Therefore, a double-blind design was not feasible because the results of the RICO test effectively unblinded the Investigator. Single-blind design was maintained due to the objective nature of the primary endpoint.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2010
• First Posted: June 28, 2010
• Study Start: January 1, 2011
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: April 4, 2023
• Results First Posted: May 29, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will share

Locations

AU (4); BU (1); IL (3); RO (1); CH (3); FR (1); DE (9); US (13); ES (3); GB (2); BE (4); IT (5)