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Key inclusion & exclusion criteria
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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.
Age minimum:
0 Years
Age maximum:
70 Years
Gender:
All
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Secondary Outcome(s)
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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)]
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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 10 timepoints up to 12 days]
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Number of Participants With Neurological symptoms
[Time Frame: Throughout the study period of approximately 70 months]
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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 10 timepoints up to 12 days]
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Assessment of Neutralizing Antibodies to ADAMTS13
[Time Frame: Start of treatment periods 1, 2 and 3: within 60 min pre-infusion and at study completion/early termination visit (up to 19 months)]
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Estimated Total Quantity of ADAMTS13 Administered During the Treatment of Acute TTP Events
[Time Frame: Throughout the study period of approximately 70 months]
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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 10 timepoints up to 12 days]
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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)]
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Assessment of Total Binding Antibodies to ADAMTS13
[Time Frame: Start of treatment periods 1, 2 and 3: within 60 min pre-infusion and at study completion/early termination visit (up to 19 months)]
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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)]
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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 10 timepoints up to 12 days]
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Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
[Time Frame: Throughout the study period of approximately 70 months]
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Number of Participants With Microangiopathic Hemolytic Anemia
[Time Frame: Throughout the study period of approximately 70 months]
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Resource Utilization: Length of Hospital Stay for Acute TTP Events
[Time Frame: Throughout the study period of approximately 70 months]
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Number of Participants With Supplemental Doses
[Time Frame: Throughout the study period of approximately 70 months]
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Time to Onset of Immunogenic Response to ADAMTS13
[Time Frame: Start of treatment periods 1, 2 and 3: within 60 min pre-infusion and at study completion/early termination visit (up to 19 months)]
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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 timepoints up to 7 days. >=12 years: within 60 min pre-infusion; and post-infusion at 10 timepoints up to 12 days]
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Assessment of Anti-Chinese Hamster Ovary (Anti-CHO) Protein Antibodies
[Time Frame: Start of treatment periods 1, 2 and 3: within 60 min pre-infusion and at study completion/early termination visit (up to 19 months)]
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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)]
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Resource Utilization: Days Missed From School or Work due to TTP-Related Illness
[Time Frame: Throughout the study period of approximately 70 months]
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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 10 timepoints up to 12 days]
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Number of Participants With Acute Thrombotic Thrombocytopenic Purpura (TTP) Events on Their Final Dose
[Time Frame: Throughout the study period of approximately 70 months]
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Percentage of Acute Thrombotic Thrombocytopenic Purpura (TTP) Events Responding to BAX 930
[Time Frame: Throughout the study period of approximately 70 months]
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Resource Utilization: Resource Utilization During Prophylaxis
[Time Frame: Throughout the study period of approximately 70 months]
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Time to Resolution of Acute TTP Events
[Time Frame: Throughout the study period of approximately 70 months]
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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 10 timepoints up to 12 days]
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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)]
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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 10 timepoints up to 12 days]
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Assessment of ADAMTS13 Activity (Pre-Infusion ADAMTS13 Levels) and Select 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 10 timepoints up to 12 days]
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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)]
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Number of Participants With Abdominal Pain
[Time Frame: Throughout the study period of approximately 70 months]
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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 10 timepoints up to 12 days]
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Number of Participants With Antibodies to ADAMTS13
[Time Frame: Throughout the study period of approximately 70 months]
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Number of Participants With Dose Modification
[Time Frame: Throughout the study period of approximately 70 months]
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Number of Participants With Thrombocytopenia
[Time Frame: Throughout the study period of approximately 70 months]
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Number of Participants With Renal Dysfunction
[Time Frame: Throughout the study period of approximately 70 months]
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