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A Study of Prophylactic and On-demand Treatment of Congenital Thrombotic Thrombocytopenic Purpura (cTTP) With BAX 930 (rADAMTS13)

IDENTIFIERS
Trial Protocol: 281102
Clinicaltrials.gov: NCT03393975
EudraCT: 2017-000858-18
JapicCTI: 194991
PURPOSE

The purpose of this study is to assess safety and efficacy of BAX 930 in the prevention and treatment of acute episodes of thrombotic thrombocytopenic purpura (TTP) in participants with severe congenital deficiency of ADAMTS13 (cTTP; defined as plasma ADAMTS13 lesser then [<] 10 percent [%], as measured by the fluorescent resonance energy transfer-VWF73 [FRETS] assay).

Recruiting
US
AT
FR
7+
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IT
JP
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Trial at a glance

What medical condition is being studied?   Congenital Thrombotic Thrombocytopenic Purpura
What is the trial testing?   BAX930, Standard of care
Are placebos part of the trial?   No
How many participants are being enrolled?   68
When is the trial being conducted?    - 
How long is participation in the trial?   Depending on date of participant enrollment and treatment regimen, the participant participation period is 20 months from enrollment to participant completion (i.e., last study visit), unless prematurely discontinued.

Key requirements

Sex   
All
Age   
Up to 70 Years
Accepts Healthy Volunteers?   
No

Trial Details / Participation Requirements

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Trial phase:   Phase 3
Trial Type:   Interventional
Trial Arms/Groups or Cohorts:   
Prophylaxis Cohort I: Participants randomized to SOC arm in prophylactic cohort will receive PK dose of their current SoC product followed by a single dose intravenous (IV) infusions of 40 International units per kilogram (IU/kg) BAX-930 ORT at 14 days later in PK I with a washout period of 14 days (+ or - 2 days). In period 1 participants will receive IV infusions of 40 IU/kg dose of BAX-930 ORT once every 2 weeks (Q2W) for 6 months followed by SOC in period 2 for the next six months. After period 2, participants will receive a single dose IV infusions of 40 IU/kg BAX-930 ORT followed by IV infusions of 40 IU/kg BAX-930 SIN in PK II with a washout period of 14 days (+ or - 2 days). All the participants in period 3 will receive BAX-930 SIN prophylactic dose of IV infusions of 40 IU/kg for another 6 months.
Prophylaxis Cohort II: Participants randomized to BAX-930 arm in prophylactic cohort will receive a single dose IV infusions of 40 IU/kg BAX-930 ORT followed by a PK dose of their current SoC product at 14 days later in PK I with a washout period of 14 days (+ or - 2 days). In period 1 participants will receive SOC for the next six months followed by IV infusions of 40 IU/kg dose of BAX-930 ORT once Q2W for 6 months in period 2. Thereafter participants will receive a single dose IV infusions of 40 IU/kg BAX-930 SIN followed by IV infusions of 40 IU/kg BAX-930 ORT in PK II with a washout period of 14 days (+ or - 2 days). All the participants in period 3 will receive BAX-930 SIN prophylactic dose IV infusions of 40 IU/kg for another 6 months.
On Demand Cohort I: Participants randomized to SOC arm in On-demand cohort will receive the investigator-recommended SOC and dosing regimen during the acute event. In period 1 participants will receive IV infusions of 40 IU/kg dose of BAX-930 ORT once every 2 weeks (Q2W) for 6 months followed by SOC in period 2 for the next six months. Thereafter participants will receive a single dose IV infusions of 40 IU/kg BAX-930 ORT followed by IV infusions of 40 IU/kg BAX-930 SIN in PK II with a washout period of 14 days (+ or - 2 days). All the participants in period 3 will receive BAX-930 SIN prophylactic dose IV infusions of 40 IU/kg for another 6 months.
On Demand Cohort II: Participants randomized to BAX-930 arm in On-demand cohort will receive initial dose of IV infusions 40 IU/kg [+/- 4 IU/kg] BAX-930 ORT or BAX-930 SIN infusion then a subsequent dose IV infusions of 20 IU/kg [+/- 2 IU/kg] BAX-930 ORT or BAX-930 SIN infusion on Day 2 and an additional daily dose IV infusions of 15 IU/kg [+/- 1.5 IU/kg] BAX 930 until 2 days after the acute event is resolved. In period 1 participants will receive SOC for the next six months followed by IV infusions of 40 IU/kg dose of BAX-930 ORT once Q2W for 6 months in period 2. Thereafter participants will receive a single dose IV infusions of 40 IU/kg BAX-930 SIN followed by IV infusions of 40 IU/kg BAX-930 ORT in PK II with a washout period of 14 days (+ or - 2 days). All the participants in period 3 will receive BAX-930 SIN prophylactic dose IV infusions of 40 IU/kg for another 6 months.
Intervention:   BAX930Standard of care
Primary Outcome Measure(s):
Number of Participants With Acute Thrombotic Thrombocytopenic Purpura (TTP) Episodes [Time Frame: Throughout the study period of approximately 69 months]
Secondary Outcome Measure(s):   
Number of Acute Thrombotic Thrombocytopenic Purpura (TTP) Episodes Responding to BAX 930 [Time Frame: Throughout the study period of approximately 69 months]
Number of Participants With Acute Thrombotic Thrombocytopenic Purpura (TTP) Episodes Responding to BAX 930 [Time Frame: Throughout the study period of approximately 69 months]
Time to Resolution of Clinical Symptomatology [Time Frame: Throughout the study period of approximately 69 months]
Number of Participants With Thrombocytopenia [Time Frame: Throughout the study period of approximately 69 months]
Number of Participants With Microangiopathic Hemolytic Anemia [Time Frame: Throughout the study period of approximately 69 months]
Number of Participants With Neurological symptoms [Time Frame: Throughout the study period of approximately 69 months]
Number of Participants With Renal Dysfunction [Time Frame: Throughout the study period of approximately 69 months]
Number of Participants With Abdominal Pain [Time Frame: Throughout the study period of approximately 69 months]
Number of Participants With Supplemental Doses [Time Frame: Throughout the study period of approximately 69 months]
Number of Participants With Dose Modification [Time Frame: Throughout the study period of approximately 69 months]
Number of Participants With Acute Thrombotic Thrombocytopenic Purpura (TTP) Episodes on Their Final Dose [Time Frame: Throughout the study period of approximately 69 months]
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time Frame: Throughout the study period of approximately 69 months]
Number of Participants With Antibodies to ADAMTS13 [Time Frame: Throughout the study period of approximately 69 months]
Number of Participants With Clinically Relevant Changes in Vital Signs [Time Frame: Throughout the study period of approximately 69 months]
Number of Participants With Clinically Relevant Changes in Clinical Chemistry [Time Frame: Throughout the study period of approximately 69 months]
Number of Participants with Clinically Relevant Changes in Hematology [Time Frame: Throughout the study period of approximately 69 months]
Estimated Total Quantity of ADAMTS13 Administered During the Treatment of Acute Events [Time Frame: Throughout the study period of approximately 69 months]
Incremental Recovery (IR) of ADMATS13 Activity and ADMATS13 Antigen for SoC Agent and BAX 930 in Plasma [Time Frame: Start of treatment periods and end of Treatment Period 2 prophylactic cohort. <12 years: within 60 min pre-infusion; and post-infusion at 6 timepoints up to 7 days. >=12 years: within 60 min pre-infusion; and post-infusion at 12 timepoints up to 12 days]
Area Under the Plasma curve [AUC] of ADMATS13 Activity and ADMATS13 Antigen for SoC Agent and BAX 930 in Plasma [Time Frame: Start of treatment periods and end of Treatment Period 2 prophylactic cohort. <12 years: within 60 min pre-infusion; and post-infusion at 6 timepoints up to 7 days. >=12 years: within 60 min pre-infusion; and post-infusion at 12 timepoints up to 12 day]
Terminal Half-Life (T1/2) of ADMATS13 Activity and ADMATS13 Antigen for SoC Agent and BAX 930 in Plasma [Time Frame: Start of treatment periods and end of Treatment Period 2 prophylactic cohort. <12 years: within 60 min pre-infusion; and post-infusion at 6 time points up to 7 days. >=12 years: within 60 min pre-infusion; and post-infusion at 12 timepoints up to 12 day]
Mean Residence Time (MRT) of ADMATS13 Activity and ADMATS13 Antigen for SoC Agent and BAX 930 in Plasma [Time Frame: Start of treatment periods and end of Treatment Period 2 prophylactic cohort. <12 years: within 60 min pre-infusion; and post-infusion at 6 timepoints up to 7 days. >=12 years: within 60 min pre-infusion; and post-infusion at 12 timepoints up to 12 days]
Clearance (CL) of ADMATS13 Activity and ADMATS13 Antigen for SoC Agent and BAX 930 in Plasma [Time Frame: Start of treatment periods and end of Treatment Period 2 prophylactic cohort. <12 years: within 60 min pre-infusion; and post-infusion at 6 timepoints up to 7 days. >=12 years: within 60 min pre-infusion; and post-infusion at 12 timepoints up to 12 days]
Volume at Steady State (Vss) of ADMATS13 Activity and ADMATS13 Antigen for SoC Agent and BAX 930 in Plasma [Time Frame: Start of treatment periods and end of Treatment Period 2 prophylactic cohort. <12 years: within 60 min pre-infusion; and post-infusion at 6 timepoints up to 7 days. >=12 years: within 60 min pre-infusion; and post-infusion at 12 timepoints up to 12 days]
Maximum Concentration (Cmax) of ADMATS13 Activity and ADMATS13 Antigen for SoC Agent and BAX 930 in Plasma [Time Frame: Start of treatment periods and end of Treatment Period 2 prophylactic cohort. <12 years: within 60 min pre-infusion; and post-infusion at 6 timepoints up to 7 days. >=12 years: within 60 min pre-infusion; and post-infusion at 12 timepoints up to 12 days]
Assessment of Von Willebrand Factor: Antigen (VWF:Ag) [Time Frame: Start of treatment periods and end of Treatment Period 2 prophylactic cohort. <12 years: within 60 min pre-infusion; and post-infusion at 6 timepoints up to 7 days. >=12 years: within 60 min pre-infusion; and post-infusion at 12 timepoints up to 12 days]
Assessment of Von Willebrand Factor: Ristocetin Cofactor Activity (VWF: RCo) [Time Frame: Start of treatment periods and end of Treatment Period 2 prophylactic cohort. <12 years: within 60 min pre-infusion; and post-infusion at 6 timepoints up to 7 days. >=12 years: within 60 min pre-infusion; and post-infusion at 12 timepoints up to 12 days]
Assessment of Von Willebrand Factor (VWF) Multimer [Time Frame: Start of treatment periods and end of Treatment Period 2 prophylactic cohort. <12 years: within 60 min pre-infusion; and post-infusion at 6 timepoints up to 7 days. >=12 years: within 60 min pre-infusion; and post-infusion at 12 timepoints up to 12 days]
Assessment of ADAMTS13 Activity (Pre-Infusion ADAMTS13 Levels) and VWF Parameters [Time Frame: Start of treatment periods and end of Treatment Period 2 prophylactic cohort. <12 years: within 60 min pre-infusion; and post-infusion at 6 timepoints up to 7 days. >=12 years: within 60 min pre-infusion; and post-infusion at 12 timepoints up to 12 days]
Health Related Quality of Life (HRQoL): cTTP-Specific Patient reported outcomes (PROs) [Time Frame: Day 0, End of period 1 (approximately 6 months), End of period 2 (approximately 12 months), and End of period 3 (approximately 19 months), or non-scheduled acute event (as needed)]
Health Related Quality of Life (HRQoL): 36-Item Short Form Health Survey (SF-36) [Time Frame: Day 0, End of period 1 (approximately 6 months), End of period 2 (approximately 12 months), and End of period 3 (approximately 19 months), or non-scheduled acute event (as needed)]
Health Related Quality of Life (HRQoL): Abbreviated 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) [Time Frame: Day 0, End of period 1 (approximately 6 months), End of period 2 (approximately 12 months), and End of period 3 (approximately 19 months), or non-scheduled acute event (as needed)]
Health Related Quality of Life (HRQoL): EuroQol 5 Dimensions Questionnaire 3-Level (EQ-5D-3L) [Time Frame: Day 0, End of period 1 (approximately 6 months), End of period 2 (approximately 12 months), and End of period 3 (approximately 19 months), or non-scheduled acute event (as needed)]
Health Related Quality of Life (HRQoL): EQ-5D-youth (EQ-5D-Y) [Time Frame: Day 0, End of period 1 (approximately 6 months), End of period 2 (approximately 12 months), and End of period 3 (approximately 19 months), or non-scheduled acute event (as needed)]
Health Related Quality of Life (HRQoL): Pediatric Quality of Life Inventory (Ped QL) [Time Frame: Day 0, End of period 1 (approximately 6 months), End of period 2 (approximately 12 months), and End of period 3 (approximately 19 months), or non-scheduled acute event (as needed)]
Resource Utilization: Length of Hospital Stay for Acute TTP Episodes [Time Frame: Throughout the study period of approximately 69 months]
Resource Utilization: Resource Utilization During Prophylaxis [Time Frame: Throughout the study period of approximately 69 months]
Resource Utilization: Days Missed From School or Work due to TTP-Related Illness [Time Frame: Throughout the study period of approximately 69 months]
Entry Criteria:
Inclusion Criteria: - Participant or legally authorized representative has provided signed informed consent greater than or equal to (>=) 18 years of age and/or assent form (signed by legal representative if participants is less than (<) 18 years of age). - Participant is 0 to 70 years of age, inclusive, at the time of screening. (Participants < 18 years of age will be enrolled only after at least 5 adults (>= 18 years of age) each have at least 10 exposures with BAX 930 and reviewed by the Data Monitoring Committee (DMC). In France, no participants younger than 18 years of age will be enrolled into the study before the first adult participant has been treated with BAX 930 for a minimum of 6 months. - Participant has a documented diagnosis of severe hereditary ADAMTS13 deficiency, defined as: - Confirmed by molecular genetic testing, documented in participant history or at screening, and - A disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13 (ADAMTS13) activity < 10 percent (%) as measured by the fluorescent resonance energy transfer- von Willebrand factor73 (FRETS-VWF73) assay, documented in participant history or at screening (participants currently receiving standard of care (SoC) prophylactic therapy may exceed 10% ADAMTS13 activity at screening). Note: Participants currently receiving prophylactic therapy will be screened immediately prior to their usual prophylactic infusion - Participant does not display any severe thrombotic thrombocytopenic purpura (TTP) signs (platelet count < 100,000/ microliter (μL) and elevation of lactate dehydrogenase (LDH) greater than (>2) × upper limit of normal (ULN)) at screening. (Prophylactic cohort only). - Participant is currently on a prophylactic dosing regimen or has a documented history of at least 1 TTP event and an ability to tolerate SoC prophylactic dosing (prophylactic cohort only). - Participants >= 16 years of age must have a Karnofsky score >= 70% and participants < 16 years of age must have a Lansky score >= 80%. - Participant is hepatitis C virus (HCV)-negative as confirmed by antibody or polymerase chain reaction testing OR HCV-positive if their disease is chronic but stable. - If female of childbearing potential, participant presents with a negative blood or urine pregnancy test, confirmed no more than 7 days before the first administration, and agrees to employ adequate birth control measures for the duration of the study and to undergo quarterly pregnancy testing. - Sexually active males must use an accepted and effective method of contraception during the treatment and until a minimum of 16 days after the last dose administered. - Participant is willing and able to comply with the requirements of the protocol. Exclusion Criteria: - Participant has been diagnosed with any other TTP-like disorder (microangiopathic hemolytic anemia), including acquired TTP. - Participant has known hypersensitivity to hamster proteins. - Participant has experienced an acute TTP episode less than 30 days prior to screening (prophylactic cohort only). - Participant has a medical history or presence of a functional ADAMTS13 inhibitor at screening. - Participant has a medical history of genetic or acquired immune deficiency that would interfere with the assessment of product immunogenicity, including participants who are human immunodeficiency virus (HIV)-positive with an absolute cluster of differentiation 4 (CD4) count < 200/ Cubic Millimeter (mm^3) or who are receiving chronic immunosuppressive drugs. - Participant has been diagnosed with severe cardiovascular disease (New York Heart Association classes 3 to 4). - Participant with end stage renal disease requiring chronic dialysis. - Participant has been diagnosed with hepatic dysfunction, as evidenced by, but not limited to, any of the following: - Serum alanine aminotransferase (ALT) >= 2× upper limit of normal (ULN). - Severe hypoalbuminemia < 24 gram per liter (g/L). - Portal vein hypertension (e.g., presence of otherwise unexplained splenomegaly, history of esophageal varices). - In the opinion of the investigator, the participant has another clinically significant concomitant disease that may pose additional risks for the participant. - Participant has been treated with an immunomodulatory drug, excluding topical treatment (e.g., ointments, nasal sprays), within 30 days prior to enrollment. Use of corticosteroids in conjunction with administration of fresh frozen plasma (FFP) to prevent allergic manifestations is permitted. - Participant has an acute illness (e.g., influenza, flu-like syndrome, allergic rhinitis/conjunctivitis, bronchial asthma) at the time of screening (prophylaxis cohort only). - Participant is receiving or anticipates receiving another investigational drug and/or interventional drug within 30 days before enrollment. - Participant has a history of drug and/or alcohol abuse within the last 2 years. - Participant has a progressive fatal disease and/or life expectancy of less than 3 months. - Participant is identified by the investigator as being unable or unwilling to cooperate with study procedures. - Participant suffers from a mental condition rendering him/her unable to understand the nature, scope, and possible consequences of the study and/or evidence of an uncooperative attitude. - Participant is a family member or employee of the sponsor or investigator. - If female, participant is pregnant or lactating at the time of enrollment. - Any contraindication to standard of care medicinal product(s) as per local prescribing information.

Trial Locations

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Recruiting
Withdrawn
Any
RESULTS
Winship Cancer Institute

1365 Clifton Rd, Atlanta, GA 30322, USA

Recruiting
6,854 miles (11,031 km)  awayfrom
日本
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Duke University Medical Center

10 Duke Medicine Cir, Durham, NC 27710, USA

Recruiting
6,885 miles (11,081 km)  awayfrom
日本
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Cincinnati Children's Hospital Medical Center

3333 Burnet Ave, Cincinnati, OH 45229, USA

Recruiting
6,541 miles (10,527 km)  awayfrom
日本
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Ohio State Univ College Of Medicine

1900 Coffey Rd, Columbus, OH 43210, USA

Recruiting
6,534 miles (10,515 km)  awayfrom
日本
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University of Oklahoma

865 Research Pkwy, Oklahoma City, OK 73104, USA

Recruiting
6,303 miles (10,143 km)  awayfrom
日本
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The Methodist Hospital

6565 Fannin St, Houston, TX 77030, USA

Recruiting
6,683 miles (10,754 km)  awayfrom
日本
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AKH - Medizinische Universität Wien

Spitalgasse 23, 1090 Wien, Austria

Recruiting
5,597 miles (9,008 km)  awayfrom
日本
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Hopital Claude Huriez - CHU Lille

Rue Michel Polonowski, 59000 Lille, France

Recruiting
5,846 miles (9,409 km)  awayfrom
日本
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CHU Saint Etienne - Hôpital Nord

Avenue Albert Raimond, 42270 Saint-Priest-en-Jarez, France

Recruiting
6,102 miles (9,821 km)  awayfrom
日本
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Hôpital Necker - Enfants Malades

149 Rue de Sèvres, 75015 Paris, France

Recruiting
5,965 miles (9,600 km)  awayfrom
日本
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Hôpital Robert Debré - Paris

Hôpital Robert Debré, Bd Sérurier, 75019 Paris, France

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5,961 miles (9,594 km)  awayfrom
日本
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Hôpital Saint-Antoine

184 Rue du Faubourg Saint-Antoine, 75012 Paris, France

Recruiting
5,963 miles (9,597 km)  awayfrom
日本
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Universitaetsklinikum Hamburg-Eppendorf

Martinistraße 52, 20251 Hamburg, Germany

Recruiting
5,505 miles (8,859 km)  awayfrom
日本
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Universitaetsklinikum Jena

Am Klinikum 1, 07747 Jena, Germany

Recruiting
5,603 miles (9,017 km)  awayfrom
日本
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Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)

Piazza OMS, 1, 24127 Bergamo BG, Italy

Recruiting
5,937 miles (9,555 km)  awayfrom
日本
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Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico

Via della Commenda, 10, 20122 Milano MI, Italy

Recruiting
5,963 miles (9,596 km)  awayfrom
日本
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Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Via della Pineta Sacchetti, 217, 00168 Roma RM, Italy

Recruiting
6,048 miles (9,733 km)  awayfrom
日本
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Kyushu University Hospital

3-chōme-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

Recruiting
501 miles (806 km)  awayfrom
日本
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Hyogo College of Medicine Hospital

1-1 Mukogawachō, Nishinomiya, Hyogo 663-8501, Japan

Recruiting
214 miles (345 km)  awayfrom
日本
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Medical Hospital, Tokyo Medical and Dental University

1-chōme-5-45 Yushima, Bunkyo City, Tōkyō-to 113-8519, Japan

Recruiting
81 miles (130 km)  awayfrom
日本
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Instytut Hematologii i Transfuzjologii

Indiry Gandhi 14, 02-776 Warszawa, Poland

Recruiting
5,259 miles (8,464 km)  awayfrom
日本
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Hospital de Cruces

Cruces Plaza, S/N, 48903 Barakaldo, Bizkaia, Spain

Recruiting
6,426 miles (10,341 km)  awayfrom
日本
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Hospital General Universitario de Alicante

Pintor Baeza, 11, 03010 Alacant, Alicante, Spain

Recruiting
6,650 miles (10,701 km)  awayfrom
日本
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Hospital Universitari i Politecnic La Fe

Avinguda de Fernando Abril Martorell, 106, 46026 València, Valencia, Spain

Recruiting
6,583 miles (10,595 km)  awayfrom
日本
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University College London Hospitals

235 Euston Rd, Bloomsbury, London NW1 2BU, UK

Recruiting
5,869 miles (9,446 km)  awayfrom
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Inselspital - Universitaetsspital Bern

Freiburgstrasse 18, 3010 Bern, Switzerland

5,934 miles (9,550 km)  awayfrom
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Trial Protocol ID: 281102
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