A Study of BAX 930 in Children, Teenagers, and Adults Born With Thrombotic Thrombocytopenic Purpura (TTP)
Thrombotic Thrombocytopenic Purpura (TTP)
About this trial
This is an interventional prevention trial for Thrombotic Thrombocytopenic Purpura (TTP)
Eligibility Criteria
Inclusion Criteria:
- Participant or legally authorized representative has provided signed informed consent >= 18 years of age and/or assent form (signed by legal representative if participants is <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
- ADAMTS13 activity < 10 % 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 (mcL) and elevation of lactate dehydrogenase (LDH) greater than (>2)* 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 event 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* 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 reactions 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 SoC medicinal product(s) as per local prescribing information.
Sites / Locations
- Winship Cancer Institute
- Alliance for Childhood Diseases, Cure 4 the Kids Foundation
- Duke University Medical CenterRecruiting
- Cincinnati Children's Hospital Medical Center
- Ohio State Univ College Of Medicine
- University of Oklahoma
- The Methodist Hospital
- AKH - Medizinische Universität Wien
- CHU Saint Etienne - Hôpital NordRecruiting
- Hopital Claude Huriez - CHU Lille
- Hôpital Saint-Antoine
- Hôpital Necker - Enfants MaladesRecruiting
- Hôpital Robert Debré - ParisRecruiting
- Universitaetsklinikum JenaRecruiting
- Universitaetsklinikum Hamburg-EppendorfRecruiting
- Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)
- Azienda Ospedaliera Universitaria "Policlinico - Vittorio Emanuele" (Presidio Ferrarotto Alessi)Recruiting
- Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- Dipartimento di Medicina Traslazionale e di Precisione - "Sapienza" Universita di RomaRecruiting
- Kyushu University Hospital
- Hyogo College of Medicine Hospital
- Medical Hospital, Tokyo Medical and Dental University
- Samodzielny Publiczny Dzieciecy Szpital Kliniczny
- Instytut Hematologii i Transfuzjologii
- Complejo Hospitalario Universitario A CoruñaRecruiting
- Hospital de Cruces
- Hospital General Universitario de Alicante
- Hospital Universitario de Salamanca
- Hospital Universitario Virgen del Rocio
- Hospital Universitari i Politecnic La FeRecruiting
- Inselspital - Universitaetsspital Bern
- University College London Hospitals
- Royal Manchester Children's Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Experimental
Experimental
Prophylaxis Cohort I
Prophylaxis Cohort II
On Demand Cohort I
On Demand Cohort II
Participants randomized to SOC arm in prophylactic treatment cohort will receive a single dose intravenous (IV) infusions of 40 international units per kilogram (IU/kg) BAX-930 ORT product followed by a PK dose of their current SoC 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 6 months followed by IV infusions of 40 IU/kg dose of BAX-930 ORT once every 2 weeks (Q2W) 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.
Participants randomized to BAX-930 arm in prophylactic cohort will receive a PK dose of their current SoC product followed by a single dose IV infusions of 40 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 a single dose IV infusions of 40 IU/kg BAX-930 ORT once Q2W for the next six months followed by SOC 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.
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.
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.