Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03393975
Recruitment Status : Recruiting
First Posted : January 9, 2018
Last Update Posted : May 13, 2020
Sponsor:
Collaborator:
Baxalta Innovations GmbH, now part of Shire
Information provided by (Responsible Party):
Shire ( Baxalta now part of Shire )

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Congenital Thrombotic Thrombocytopenic Purpura Biological: BAX930 Biological: Standard of care Phase 3

Detailed Description:
This study consists of 2 cohorts with total duration of 69 months. 1) Prophylaxis Treatment Cohort: This cohort consists of 3 periods (period 1, 2, 3) and 2 cross-over pharmacokinetic (PK I and PK II) assessments with a washout period of 14 days (+ or - 2 days) between the doses in PK . Participants in prophylaxis cohort will be randomized equally to 1 of 2 treatment orders either BAX 930-SoC or SoC-BAX 930. 2) On-Demand Treatment Cohort: Participants in on-demand cohort will be randomized to receive urgent treatment with either the SoC or BAX 930. Upon resolution of the acute event, participants may choose to move to the prophylaxis cohort of the study or discontinue entirely. Participants electing to move to the prophylaxis cohort will move directly to Period 1 and will not be part of PK 1 evaluation. Participants who will randomize to receive BAX 930 in the on-demand arm, will receive BAX 930 ORT until BAX 930 SIN becomes available.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 68 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: This is a Phase 3, prospective, randomized, controlled, open-label, multicenter, 2-period crossover study with a single arm continuation evaluating the safety and efficacy of BAX 930 in the prophylactic and on-demand treatment of participants with severe congenital thrombotic thrombocytopenic purpura (cTTP).
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Phase 3, Prospective, Randomized, Controlled, Open-Label, Multicenter, 2-Period Crossover Study With a Single Arm Continuation Evaluating the Safety and Efficacy of BAX 930 (rADAMTS13) in the Prophylactic and On-demand Treatment of Participants With Severe Congenital Thrombotic Thrombocytopenic Purpura (cTTP) (Upshaw-Schulman Syndrome)
Actual Study Start Date : October 20, 2017
Estimated Primary Completion Date : February 1, 2023
Estimated Study Completion Date : June 1, 2023


Arm Intervention/treatment
Experimental: 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.
Biological: BAX930
Participants in prophylaxis cohort will receive IV infusions of 40 IU/kg BAX 930 ORT during Period 1 and Period 2 and switch to BAX 930 SIN during Period 3 for six months once in a week or twice in a week. In On-demand cohort participants will receive daily IV dose of BAX-930.
Other Names:
  • rADAMTS13
  • SHP-655
  • TAK-755
  • recombinant ADAMTS13
  • BAX 930

Biological: Standard of care
Participants will receive Investigator-recommended Standard of care (SoC).

Experimental: 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.
Biological: BAX930
Participants in prophylaxis cohort will receive IV infusions of 40 IU/kg BAX 930 ORT during Period 1 and Period 2 and switch to BAX 930 SIN during Period 3 for six months once in a week or twice in a week. In On-demand cohort participants will receive daily IV dose of BAX-930.
Other Names:
  • rADAMTS13
  • SHP-655
  • TAK-755
  • recombinant ADAMTS13
  • BAX 930

Biological: Standard of care
Participants will receive Investigator-recommended Standard of care (SoC).

Experimental: 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.
Biological: BAX930
Participants in prophylaxis cohort will receive IV infusions of 40 IU/kg BAX 930 ORT during Period 1 and Period 2 and switch to BAX 930 SIN during Period 3 for six months once in a week or twice in a week. In On-demand cohort participants will receive daily IV dose of BAX-930.
Other Names:
  • rADAMTS13
  • SHP-655
  • TAK-755
  • recombinant ADAMTS13
  • BAX 930

Biological: Standard of care
Participants will receive Investigator-recommended Standard of care (SoC).

Experimental: 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.
Biological: BAX930
Participants in prophylaxis cohort will receive IV infusions of 40 IU/kg BAX 930 ORT during Period 1 and Period 2 and switch to BAX 930 SIN during Period 3 for six months once in a week or twice in a week. In On-demand cohort participants will receive daily IV dose of BAX-930.
Other Names:
  • rADAMTS13
  • SHP-655
  • TAK-755
  • recombinant ADAMTS13
  • BAX 930

Biological: Standard of care
Participants will receive Investigator-recommended Standard of care (SoC).




Primary Outcome Measures :
  1. Number of Participants With Acute Thrombotic Thrombocytopenic Purpura (TTP) Episodes [ Time Frame: Throughout the study period of approximately 69 months ]
    Number of participants with acute TTP episodes among participants receiving either BAX 930 or standard of care (SoC) prophylactically during the corresponding treatment periods will be assessed.


Secondary Outcome Measures :
  1. Number of Acute Thrombotic Thrombocytopenic Purpura (TTP) Episodes Responding to BAX 930 [ Time Frame: Throughout the study period of approximately 69 months ]
    Number of acute thrombotic thrombocytopenic purpura episodes responding to BAX 930, is defined as not requiring the use of another ADAMTS13-containing agent.

  2. Number of Participants With 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 episodes responding to BAX 930, is defined as not requiring the use of another ADAMTS13-containing agent.

  3. Time to Resolution of Clinical Symptomatology [ Time Frame: Throughout the study period of approximately 69 months ]
    Time to resolution of clinical symptomatology, if present, and normalization of laboratory parameters platelet count greater than or equal to (>=) 150,000/microliters (mcL); lactate dehydrogenase (LDH) lesser than or equal to (<=)1.5×upper limit of normal (ULN) following initiation of treatment in acute TTP episodes with BAX 930 or standard of care (SoC) agent.

  4. Number of Participants With Thrombocytopenia [ Time Frame: Throughout the study period of approximately 69 months ]
    Thrombocytopenia is defined as a drop in platelet count >= 25 percent (%) of baseline or a platelet count lesser than (<) 150,000/mcgL. Number of participants with thrombocytopenia will be assessed.

  5. Number of Participants With Microangiopathic Hemolytic Anemia [ Time Frame: Throughout the study period of approximately 69 months ]
    Microangiopathic hemolytic anemia is defined as an elevation of LDH greater than (>) 1.5× ULN. Number of participants with microangiopathic hemolytic anemia will be assessed.

  6. Number of Participants With Neurological symptoms [ Time Frame: Throughout the study period of approximately 69 months ]
    Neurological symptoms includes (e.g., confusion, dysphonia, dysarthria, focal or general motor symptoms including seizures). Number of participants with neurological symptoms will be assessed.

  7. Number of Participants With Renal Dysfunction [ Time Frame: Throughout the study period of approximately 69 months ]
    Renal dysfunction is defined as an increase in serum creatinine >1.5× baseline at screening. Number of participants with renal dysfunction will be assessed.

  8. Number of Participants With Abdominal Pain [ Time Frame: Throughout the study period of approximately 69 months ]
    Number of participants with abdominal pain in the prophylactic cohort will be assessed.

  9. Number of Participants With Supplemental Doses [ Time Frame: Throughout the study period of approximately 69 months ]
    Number of participants with supplemental doses prompted by subacute manifestations will be assessed.

  10. Number of Participants With Dose Modification [ Time Frame: Throughout the study period of approximately 69 months ]
    Number of participants with dose modification not prompted by an acute event will be assessed.

  11. 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 acute TTP episodes on their final dose and dosing regimen for the prophylactic cohort will be assessed.

  12. Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Throughout the study period of approximately 69 months ]
    An AE is defined as any untoward medical occurrence in a participants administered an IP that does not necessarily have a causal relationship with the treatment. A SAE is defined as an untoward medical occurrence that at any dose meets 1 or more of the following criteria: death; initial or prolonged in-patient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly, medically important event (may not be immediately lifethreatening or result in death or require hospitalization but may require medical or surgical intervention to prevent 1 of the other outcomes: intensive treatment, confirmed seroconversion for human immunodeficiency viruses (HIV), severe hypersensitivity/allergic reactions, uncomplicated pregnancies etc).

  13. Number of Participants With Antibodies to ADAMTS13 [ Time Frame: Throughout the study period of approximately 69 months ]
    Number of participants with binding and inhibitory antibodies to ADAMTS13 will be assessed.

  14. Number of Participants With Clinically Relevant Changes in Vital Signs [ Time Frame: Throughout the study period of approximately 69 months ]
    Vital signs includes pulse rate, blood pressure, respiration rate, and temperature. Number of participants with clinical relevant changes in vital signs will be reported.

  15. Number of Participants With Clinically Relevant Changes in Clinical Chemistry [ Time Frame: Throughout the study period of approximately 69 months ]
    Clinical laboratory evaluations includes clinical chemistry (sodium, potassium, chloride, alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), bilirubin, alkaline phosphatase, blood urea nitrogen, creatinine, and glucose). Number of participants with clinically relevant changes in clinical laboratory evaluations will be reported.

  16. Number of Participants with Clinically Relevant Changes in Hematology [ Time Frame: Throughout the study period of approximately 69 months ]
    Hematology includes red blood cell (RBC) count, hemoglobin, hematocrit, haptoglobin, reticulocyte count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), leukocytes (i.e., white blood cell count) with differential (i.e., basophils, eosinophils, lymphocytes, monocytes, and neutrophils) and platelet counts. Number of participants with clinically relevant changes in Hematology will be reported.

  17. Estimated Total Quantity of ADAMTS13 Administered During the Treatment of Acute Events [ Time Frame: Throughout the study period of approximately 69 months ]
    Estimated total quantity of ADAMTS13 administered during the treatment of acute events will be assessed. Acute events typically require 3-4 days of intensified treatment.

  18. 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 ]
    ADAMTS13 activity will be measured by the fluorescent resonance energy transfer (FRETS) assay, ADAMTS13 antigen will be measured using a commercial ADAMTS13 enzyme-linked immunosorbent assay (ELISA) employing ADAMTS13 antigen. IR is defined as body weight normalized maximum increase in plasma ADAMTS13 antigen and activity level. IR of ADMATS13 activity and ADMATS13 antigen for SoC agent and BAX 930 in plasma will be assessed.

  19. 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 ]
    AUC of ADMATS13 activity and ADMATS13 antigen for SoC agent and BAX 930 in plasma will be assessed.

  20. 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 ]
    T1/2 of ADMATS13 activity and ADMATS13 antigen for SoC agent and BAX 930 in plasma will be assessed.

  21. 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 ]
    MRT of ADMATS13 activity and ADMATS13 antigen for SoC agent and BAX 930 in plasma will be assessed.

  22. 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 ]
    CL of ADMATS13 activity and ADMATS13 antigen for SoC agent and BAX 930 in plasma will be assessed.

  23. 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 ]
    Vss of ADMATS13 activity and ADMATS13 antigen for SoC agent and BAX 930 in plasma will be assessed.

  24. 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 ]
    Cmax of ADMATS13 activity and ADMATS13 antigen for SoC agent and BAX 930 in plasma will be assessed.

  25. 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 ]
    VWF:Ag is a measure of total VWF protein and will be assessed using a sandwich ELISA employing polyclonal anti-human-VWF antibodies. Assessments of VWF:Ag at baseline and following infusion of the SoC agent and BAX 930 treatment during the initial PK assessment will be reported.

  26. 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 ]
    VWF:RCo will provide a measure of the ability of VWF to bind platelet glycoprotein Ib. Stabilized platelets are agglutinated in the presence of VWF and the antibiotic Ristocetin. Assessments of VWF:RCo at baseline and following infusion of the SoC agent and BAX 930 treatment during the initial PK assessment will be reported.

  27. 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 ]
    VWF multimer pattern (small, intermediate, large, and ultra large) will be assessed using low-resolution sodium dodecyl sulfate (SDS)-agarose gel electrophoresis. Assessments of VWF multimer at baseline and following infusion of the SoC agent and BAX 930 treatment during the initial PK assessment will be reported.

  28. 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 ]
    Assessment of ADAMTS13 activity (pre-infusion ADAMTS13 levels) and VWF parameters prior to each infusion of SoC or BAX 930 and at the time of acute event presentation will be reported.

  29. 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) ]
    The congenital thrombotic thrombocytopenic purpura (cTTP)-specific patient-reported outcomes (PRO) instrument consists of 26 questions designed to assess the patient's experience of fatigue, joint, muscle, abdominal and chest pain in the previous 24 hours, neurologic manifestations, bruising, feelings of depression and mood alterations, and activity limitation in the past 7 days, and patient's attitudes, experienced side effects, work/school absences and travel impact associated with treatment received for TTP during the previous 2 weeks. The cTTP PRO assessment is focused on measuring the symptoms and impacts of the disease. The scores range from 0 to 152. Higher scores indicate a better quality of life.

  30. 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) ]
    The SF-36 is a generic quality-of-life instrument that has been widely used to assess health-related quality of life (HRQoL) of participants. Generic instruments are used in general populations to assess a wide range of domains applicable to a variety of health states, conditions, and diseases. The SF-36 consists of 36 items that are aggregated into 8 multi-item scales (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health), with scores ranging from 0 to 100. Higher scores indicate better HRQoL.

  31. 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) ]
    TSQM is a global satisfaction scale used to assess the overall level of participant's satisfaction or dissatisfaction with their medications. TSQM-9 is a 9-item, validated, self-administered instrument used to assess participant's satisfaction with medication. The three domains assessed are effectiveness, convenience, and global satisfaction. The score of each of the 3 domains is based on an algorithm to create a score of 0 to 100. Higher score indicated greater satisfaction in that domain.

  32. 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) ]
    EQ-5D-3L health questionnaire is a participant answered questionnaire scoring 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The EQ-5D total score ranges from 0 (worst health state) to 1 (perfect health state) and 1 reflects the best outcome.

  33. 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) ]
    EQ-5D-Y health questionnaire is a participant answered questionnaire scoring 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The EQ-5D total score ranges from 0 (worst health state) to 1 (perfect health state) and 1 reflects the best outcome.

  34. 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) ]
    The Peds QL is a generic health related quality of life instrument designed specifically for a pediatric population and captures following domains: physical functioning, emotional functioning, social functioning, school functioning, psychosocial summary, physical health and total score. The Peds-QL total score consist of all 23 items of all domains. This modular instrument uses a 5-point scale: from 0 (never) to 4 (almost always). Items are reversed scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. Higher scores indicate better quality of life.

  35. Resource Utilization: Length of Hospital Stay for Acute TTP Episodes [ Time Frame: Throughout the study period of approximately 69 months ]
    Number of days participants stay in hospital for Acute TTP episodes will be assessed.

  36. Resource Utilization: Resource Utilization During Prophylaxis [ Time Frame: Throughout the study period of approximately 69 months ]
    Number of participants utilized during prophylaxis will be assessed.

  37. Resource Utilization: Days Missed From School or Work due to TTP-Related Illness [ Time Frame: Throughout the study period of approximately 69 months ]
    Number of days missed from school or work due to TTP-related illness will be assessed.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   up to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03393975


Contacts
Layout table for location contacts
Contact: Shire Contact +1 866 842 5335 ClinicalTransparency@shire.com

Locations
Show Show 22 study locations
Sponsors and Collaborators
Baxalta now part of Shire
Baxalta Innovations GmbH, now part of Shire
Investigators
Layout table for investigator information
Study Director: Study Director Shire
Layout table for additonal information
Responsible Party: Baxalta now part of Shire
ClinicalTrials.gov Identifier: NCT03393975    
Other Study ID Numbers: 281102
2017-000858-18 ( EudraCT Number )
First Posted: January 9, 2018    Key Record Dates
Last Update Posted: May 13, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Shire provides access to the de-identified individual participant data for eligible studies to aid qualified researchers in addressing legitimate scientific objectives. These IPDs will be provided following approval of a data sharing request, and under the terms of a data sharing agreement.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.shiretrials.com website. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
URL: https://www.shiretrials.com/en/our-commitment-to-transparency/data-sharing-with-researchers

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Purpura
Purpura, Thrombocytopenic
Purpura, Thrombotic Thrombocytopenic
Blood Coagulation Disorders
Hematologic Diseases
Hemorrhage
Pathologic Processes
Skin Manifestations
Thrombotic Microangiopathies
Thrombocytopenia
Blood Platelet Disorders
Immune System Diseases
Thrombophilia