Clinical trial NCT02553317: Phase III Trial With Caplacizumab in Patients With Acquired Thrombotic Thrombocytopenic Purpura
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acquired Thrombotic Thrombocytopenic Purpura
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2015-09-17
Enrollment: 145
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Time to Platelet Count Response
timeFrame: 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:
measure: Number and Percentage of Subjects With TTP-Related Death, Recurrence of TTP, or a Major Thromboembolic Event During the Study Drug Treatment Period
timeFrame: 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.
measure: Number and Percentage of Subjects With a Recurrence of TTP in the Overall Study Period
timeFrame: The overall study period (covers both the overall treatment period and the follow-up period), a median (min, max) of 65 (2, 110) days.
measure: Number and Percentage of Subjects With Refractory Disease
timeFrame: The study drug treatment period, a median (min, max) of 36 (2, 82) days.
measure: Time to Normalization of Organ Damage Marker Levels
timeFrame: 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:
measure: Number of Days of Plasma Exchange
timeFrame: Overall study drug treatment period, a median (min, max) of 36 (2, 82) days.
measure: Total Volume of Plasma Exchange
timeFrame: Overall study drug treatment period, a median (min, max) of 36 (2, 82) days.
measure: Number of Days in Intensive Care Unit
timeFrame: Overall study drug treatment period, a median (min, max) of 36 (2, 82) days.
measure: Number of Days in Hospital
timeFrame: Overall study drug treatment period, a median (min, max) of 36 (2, 82) days.
Locations:
city: Birmingham
country: United States
facility: Investigator Site
state: Alabama
city: Los Angeles
country: United States
facility: Investigator Site
state: California
city: Atlanta
country: United States
facility: Investigator Site
state: Georgia
city: Boston
country: United States
facility: Investigator Site
state: Massachusetts
city: Saint Louis
country: United States
facility: Investigator Site
state: Missouri
city: Rochester
country: United States
facility: Investigator Site
state: New York
city: Rochester
country: United States
facility: Investigator Site
state: New York
city: Valhalla
country: United States
facility: Investigator Site
state: New York
city: Chapel Hill
country: United States
facility: Investigator Site
state: North Carolina
city: Durham
country: United States
facility: Investigator Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Investigator Site
state: North Carolina
city: Cleveland
country: United States
facility: Investigator SIte
state: Ohio
city: Columbus
country: United States
facility: Investigator Site
state: Ohio
city: Oklahoma City
country: United States
facility: Investigator Site
state: Oklahoma
city: Pittsburgh
country: United States
facility: Investigator Site
state: Pennsylvania
city: Charleston
country: United States
facility: Investigator Site
state: South Carolina
city: Greenville
country: United States
facility: Investigator Site
state: South Carolina
city: Houston
country: United States
facility: Investigator Site
state: Texas
city: Salt Lake City
country: United States
facility: Investigator Site
state: Utah
city: Brisbane
country: Australia
facility: Investigator Site
city: Melbourne
country: Australia
facility: Investigator Site 1
city: Melbourne
country: Australia
facility: Investigator Site 2
city: Melbourne
country: Australia
facility: Investigator Site 3
city: Melbourne
country: Australia
facility: Investigator Site 4
city: Melbourne
country: Australia
facility: Investigator Site 5
city: Perth
country: Australia
facility: Investigator Site
city: Sydney
country: Australia
facility: Investigator Site 1
city: Sydney
country: Australia
facility: Investigator Site 2
city: Vienna
country: Austria
facility: Investigator Site
city: Antwerp
country: Belgium
facility: Investigator Site
city: Brussels
country: Belgium
facility: Investigator Site
city: Haine-Saint-Paul
country: Belgium
facility: Investigator Site
city: La Louviere
country: Belgium
facility: Investigator Site
city: Leuven
country: Belgium
facility: Investigator Site
city: Montreal
country: Canada
facility: Invesigator Site
state: Quebec
city: London
country: Canada
facility: Investigator Site
city: Toronto
country: Canada
facility: Investigator Site
city: Brno
country: Czechia
facility: Investigator Site
city: Hradec Kralove
country: Czechia
facility: Investigator Site
city: Olomouc
country: Czechia
facility: Investigator Site
city: Ostrava-Poruba
country: Czechia
facility: Investigator Site
city: Caen
country: France
facility: Investigator Site
city: Lille
country: France
facility: Investigator Site
city: Marseille
country: France
facility: Investigator Site
city: Nantes
country: France
facility: Investigator Site
city: Paris
country: France
facility: Investigator Site 1
city: Paris
country: France
facility: Investigator Site 2
city: Paris
country: France
facility: Investigator Site 3
city: Paris
country: France
facility: Investigator Site 4
city: Paris
country: France
facility: Investigator site 5
city: Rouen
country: France
facility: Investigator Site
city: Salouel
country: France
facility: Investigator Site
city: Dresden
country: Germany
facility: Investigator site 1
city: Dresden
country: Germany
facility: Investigator site 2
city: Erlangen
country: Germany
facility: Investigator site
city: Goppingen
country: Germany
facility: Investigator site
city: Kiel
country: Germany
facility: Investigator site
city: Köln
country: Germany
facility: Investigator site
city: Leipzig
country: Germany
facility: Investigator site
city: Würzburg
country: Germany
facility: Investigator site
city: Budapest
country: Hungary
facility: Investigator Site 1
city: Budapest
country: Hungary
facility: Investigator Site 2
city: Debrecen
country: Hungary
facility: Investigator Site
city: Be'er Ya'aqov
country: Israel
facility: Investigator Site 1
city: Be'er Ya'aqov
country: Israel
facility: Investigator Site 2
city: Haifa
country: Israel
facility: Investigator Site
city: Jerusalem
country: Israel
facility: Investigator Site 1
city: Jerusalem
country: Israel
facility: Investigator Site 2
city: Nahariya
country: Israel
facility: Investigator Site
city: Petah Tiqva
country: Israel
facility: Investigator Site
city: Tel Aviv
country: Israel
facility: Investigator Site
city: Catania
country: Italy
facility: Investigator Site
city: Milan
country: Italy
facility: Investigator Site 1
city: Milan
country: Italy
facility: Investigator Site 2
city: Pesaro
country: Italy
facility: Investigator Site
city: Rome
country: Italy
facility: Investigator Site
city: Vicenza
country: Italy
facility: Investigator Site
city: Amersfoort
country: Netherlands
facility: Investigator Site
city: Leiden
country: Netherlands
facility: Investigator Site
city: Rotterdam
country: Netherlands
facility: Investigator Site
city: Veldhoven
country: Netherlands
facility: Investigator Site
city: Barcelona
country: Spain
facility: Investigator Site 1
city: Barcelona
country: Spain
facility: Investigator Site 2
city: Madrid
country: Spain
facility: Investigator Site
city: Sevilla
country: Spain
facility: Investigator Site
city: Valencia
country: Spain
facility: Investigator Site 1
city: Valencia
country: Spain
facility: Investigator Site 2
city: Valencia
country: Spain
facility: Investigator site 3
city: Bern
country: Switzerland
facility: Investigator Site
city: Zurich
country: Switzerland
facility: Investigator Site
city: Ankara
country: Turkey
facility: Investigator Site
city: Denizli
country: Turkey
facility: Investigator Site 1
city: Denizli
country: Turkey
facility: Investigator Site 2
city: Denizli
country: Turkey
facility: Investigator site 3
city: Istanbul
country: Turkey
facility: Investigator Site
city: Kayseri
country: Turkey
facility: Investigator Site
city: Trabzon
country: Turkey
facility: Investigator Site
city: Bristol
country: United Kingdom
facility: Investigator Site
city: Liverpool
country: United Kingdom
facility: Investigator Site
city: London
country: United Kingdom
facility: Investigator Site 1
city: London
country: United Kingdom
facility: Investigator Site 2
Study officials:
affiliation: Ablynx NV
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.