A Study of BAX 930 in Children, Teenagers, and Adults Born With Thrombotic Thrombocytopenic Purpura (TTP)

• ClinicalTrials.gov Identifier: NCT03393975
• Recruitment Status: Recruiting
• First Posted: January 9, 2018
• Last Update Posted: February 28, 2024
• Sponsor: Baxalta now part of Shire
• Collaborator: Takeda Development Center Americas, Inc.
• Information provided by (Responsible Party): Takeda ( Baxalta now part of Shire )

Study Description

Brief Summary:

Thrombotic thrombocytopenic purpura (or TTP for short) is a condition where blood clots form in small blood vessels throughout the body. The clots can limit or block the flow of oxygen-rich blood to the body's organs, such as the brain, kidneys, and heart. As a result, serious health problems can develop. The increased clotting that occurs in TTP uses up the cells that help the blood to clot, called platelets. With fewer platelets available in the blood, bleeding problems can occur. People who have TTP may bleed underneath the skin forming purple bruises or purpura, or from the surface of the skin. TTP also can cause anemia, a condition in which red blood cells break apart faster than the body can replace them leading to lower than normal number of red blood cells.

A lack of activity in the ADAMTS13 enzyme, a protein in the blood involved in blood clotting, causes TTP. The enzyme breaks up another blood protein called von Willebrand factor that clumps together with platelets to form blood clots. Some people are born with this condition, others get the condition during their life. Many people who born with TTP experience frequent flareups that need to be treated right away. If not treated It can be fatal or cause lasting damage, such as brain damage or a stroke. BAX 930 is a medicine that replaces ADAMTS13 and can prevent or control TTP flareups, called TTP events.

The main aim of this study is to compare the number of TTP events in people born with severe TTP when they treated with BAX 930 versus when they are treated with the standard treatment. Treatment will be given in 2 ways:

• BAX 930 or standard treatment given to prevent TTP events from happening.
• BAX 930 or standard treatment given to control an acute TTP event when it happens, according to the clinic's standard practice.

Both BAX 930 and standard treatment are given slowly through a vein (infusion).

At the first visit, the study doctor will check if you can participate in the study. If you are eligible and enter the study, you will follow an assigned schedule and either start with BAX 930 (Period 1) and then switch to standard treatment (Period 2) or start with standard treatment (Period 1) and then switch to BAX 930 (Period 2). Everyone will be treated with BAX 930 again for Period 3. Each Period will last approximately 6 months.

If you enter the study to control an acute TTP event, you will follow a schedule receiving either BAX 930 or standard care to treat your acute TTP event. Once the acute TTP event has gotten better, you can decide to continue in the study and be given treatment to prevent TTP events from happening, following the schedule above.

Another study's aim is to assess side effects from treatment with BAX 930 and standard treatment. To do that, the study doctor will ask you questions about your health at each study visit.

The study doctors will also check how long BAX 930 stays in the blood of the participants, over time. They will do this from blood samples taken after participants receive their specific infusions of BAX 930. This will happen at different times during the study.

1 month after all treatment has been completed, participants will visit the clinic for a final check-up.

Condition or disease	Intervention/treatment	Phase
Thrombotic Thrombocytopenic Purpura (TTP)	Biological: BAX930; Biological: Standard of care	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 57 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 Subjects With Severe Congenital Thrombotic Thrombocytopenic Purpura (cTTP, Upshaw-Schulman Syndrome [USS], Hereditary Thrombotic Thrombocytopenic Purpura [hTTP])
• Actual Study Start Date: October 13, 2017
• Estimated Primary Completion Date: June 28, 2024
• Estimated Study Completion Date: June 28, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Prophylaxis Cohort I; 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.	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 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.	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).

Outcome Measures

Primary Outcome Measures :

1. Number of Acute Thrombotic Thrombocytopenic Purpura (TTP) Events [ Time Frame: Throughout the study period of approximately 70 months ]
   Number of acute TTP events among participants receiving either BAX 930 or standard of care (SoC) prophylactically during the corresponding treatment periods will be assessed.

Secondary Outcome Measures :

1. Percentage of Acute Thrombotic Thrombocytopenic Purpura (TTP) Events Responding to BAX 930 [ Time Frame: Throughout the study period of approximately 70 months ]
   Percentage of acute TTP events responding to BAX 930, is defined as not requiring the use of another a human disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13 (ADAMTS13)-containing agent.
2. Time to Resolution of Acute TTP Events [ Time Frame: Throughout the study period of approximately 70 months ]
   Time to resolution of acute TTP events following initiation of treatment with BAX 930 or SoC agent will be assessed.
3. Number of Participants With Thrombocytopenia [ Time Frame: Throughout the study period of approximately 70 months ]
   Thrombocytopenia is defined as a drop in platelet count greater than or equal to (>=) 25 percent (%) of baseline or a platelet count less than (<) 150,000/mcgL reported by treatment arm for the prophylactic cohort.
4. Number of Participants With Microangiopathic Hemolytic Anemia [ Time Frame: Throughout the study period of approximately 70 months ]
   Microangiopathic hemolytic anemia is defined as an elevation of LDH greater than (>) 1.5* of baseline or >1.5* upper limit of normal (ULN) will be reported by treatment arm for the prophylactic cohort.
5. Number of Participants With Neurological symptoms [ Time Frame: Throughout the study period of approximately 70 months ]
   Neurological symptoms includes (e.g., confusion, dysphonia, dysarthria, focal or general motor symptoms including seizures will be reported by treatment arm for the prophylactic cohort.
6. Number of Participants With Renal Dysfunction [ Time Frame: Throughout the study period of approximately 70 months ]
   Renal dysfunction is defined as an increase in serum creatinine >1.5*baseline. Number of participants with renal dysfunction will be reported by treatment arm for the prophylactic cohort.
7. Number of Participants With Abdominal Pain [ Time Frame: Throughout the study period of approximately 70 months ]
   Number of participants with abdominal pain (TTP related) will be reported by treatment arm for the prophylactic cohort.
8. Number of Participants With Supplemental Doses [ Time Frame: Throughout the study period of approximately 70 months ]
   Number of participants with supplemental doses prompted by subacute TTP events will be reported by treatment for the prophylactic cohort.
9. Number of Participants With Dose Modification [ Time Frame: Throughout the study period of approximately 70 months ]
   Number of participants with dose modification not prompted by an acute TTP event will be reported by treatment for the prophylactic cohort.
10. Number of Participants With Acute Thrombotic Thrombocytopenic Purpura (TTP) Events on Their Final Dose [ Time Frame: Throughout the study period of approximately 70 months ]
    Number of participants with acute TTP events on their final dose and dosing regimen for the prophylactic cohort will be reported.
11. Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Throughout the study period of approximately 70 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). Vital signs, clinical chemistry, hematology will be assessed and reported as AE.
12. Number of Participants With Antibodies to ADAMTS13 [ Time Frame: Throughout the study period of approximately 70 months ]
    Number of participants with binding and inhibitory antibodies to ADAMTS13 will be reported.
13. Estimated Total Quantity of ADAMTS13 Administered During the Treatment of Acute TTP Events [ Time Frame: Throughout the study period of approximately 70 months ]
    Estimated total quantity of ADAMTS13 administered during the treatment of acute TTP events will be assessed. Acute TTP events typically require 3-4 days of intensified treatment.
14. 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 ]
    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.
15. 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 ]
    AUC of ADMATS13 activity and ADMATS13 antigen for SoC agent and BAX 930 in plasma will be reported.
16. 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 ]
    T1/2 of ADMATS13 activity and ADMATS13 antigen for SoC agent and BAX 930 in plasma will be reported.
17. 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 ]
    MRT of ADMATS13 activity and ADMATS13 antigen for SoC agent and BAX 930 in plasma will be reported.
18. 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 ]
    CL of ADMATS13 activity and ADMATS13 antigen for SoC agent and BAX 930 in plasma will be reported.
19. 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 ]
    Vss of ADMATS13 activity and ADMATS13 antigen for SoC agent and BAX 930 in plasma will be reported.
20. 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 ]
    Cmax of ADMATS13 activity and ADMATS13 antigen for SoC agent and BAX 930 in plasma will be reported.
21. 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 ]
    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.
22. 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 ]
    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.
23. 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 ]
    Assessment of ADAMTS13 activity (pre-infusion ADAMTS13 levels) and select VWF parameters prior to each PK infusion of SoC or BAX 930 will be reported.
24. 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) ]
    Total binding antibodies to ADAMTS13 will be measured by an ELISA-based assay, detecting total immunoglobulins (IgG, IgA, and IgM). Assessment of total antibodies at baseline, start of each treatment periods and at study completion/early termination will be reported.
25. 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) ]
    Neutralizing antibodies will be measured by a Bethesda method with Nijmegen modification using the ADAMTS13 FRETS-VWF73 activity assay. Assessment of neutralizing antibodies at baseline, start of each treatment periods and at study completion/early termination will be reported.
26. 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) ]
    Total immunoglobulin antibodies (Immunoglobulin G [IgG], A [IgA], and M [IgM]) against CHO protein will be analyzed using ELISA assay. Anti-CHO protein at baseline, start of each treatment periods and at study completion/early termination will be reported.
27. 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) ]
    Immunogenic response will assessed with the presence of total binding antibodies. Absence of total binding antibodies to ADAMTS13 is an indication of the absence of neutralizing (activity inhibition) antibodies to ADAMTS13. Time to onset of immunogenic response will be reported
28. 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.
29. 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.
30. 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.
31. 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.
32. 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.
33. 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.
34. Resource Utilization: Length of Hospital Stay for Acute TTP Events [ Time Frame: Throughout the study period of approximately 70 months ]
    Number of days participants stay in hospital for Acute TTP events will be assessed.
35. Resource Utilization: Resource Utilization During Prophylaxis [ Time Frame: Throughout the study period of approximately 70 months ]
    Number of participants utilized during prophylaxis will be assessed.
36. Resource Utilization: Days Missed From School or Work due to TTP-Related Illness [ Time Frame: Throughout the study period of approximately 70 months ]
    Number of days missed from school or work due to TTP-related illness will be assessed.

Eligibility Criteria

• Ages Eligible for Study: 0 Years 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 >= 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.

Contacts and Locations

Contacts

Contact: Shire Contact; +1 866 842 5335; ClinicalTransparency@takeda.com

Locations

United States, Georgia

Winship Cancer Institute; Completed

Atlanta, Georgia, United States, 30322

United States, Nevada

Alliance for Childhood Diseases, Cure 4 the Kids Foundation; Completed

Las Vegas, Nevada, United States, 89135

United States, North Carolina

Duke University Medical Center; Recruiting

Durham, North Carolina, United States, 27710

Contact: Site Contact 919-684-5350 thomas.ortel@duke.edu

Principal Investigator: Thomas Ortel

United States, Ohio

Cincinnati Children's Hospital Medical Center; Completed

Cincinnati, Ohio, United States, 45229

Ohio State Univ College Of Medicine; Completed

Columbus, Ohio, United States, 43210

United States, Oklahoma

University of Oklahoma; Completed

Oklahoma City, Oklahoma, United States, 73104

United States, Texas

The Methodist Hospital; Completed

Houston, Texas, United States, 77030

Austria

AKH - Medizinische Universität Wien; Completed

Vienna, Austria, 1090

France

CHU Saint Etienne - Hôpital Nord; Recruiting

Saint-Priest-en-Jarez cedex, Loire, France, 42270

Contact: Site Contact +33477828038 claire.berger@chu-st-etienne.fr

Principal Investigator: Claire Berger

Hopital Claude Huriez - CHU Lille; Completed

Lille, Nord, France, 59037

Hôpital Saint-Antoine; Completed

Paris cedex 12, Paris, France, 75571

Hôpital Necker - Enfants Malades; Recruiting

Paris cedex 15, Paris, France, 75015

Contact: Site Contact +33144497210 nathalie.biebuyck@aphp.fr

Principal Investigator: Nathalie Biebuyck

Hôpital Robert Debré - Paris; Recruiting

Paris, France, 75019

Contact: Site Contact +33140032467 claire.dossier@aphp.fr

Principal Investigator: Claire Dossier

Germany

Universitaetsklinikum Jena; Recruiting

Jena, Thueringen, Germany, 07747

Contact: Site Contact +4936418769 karim.kentouche@med.uni-jena.de

Principal Investigator: Karim Kentouche

Universitaetsklinikum Hamburg-Eppendorf; Recruiting

Hamburg, Germany, 20246

Contact: Site Contact +4940741053796 hassenpflug@uke.de

Principal Investigator: Wolf-Achim Hassenpflug

Italy

Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII); Completed

Bergamo, Italy, 24127

Azienda Ospedaliera Universitaria "Policlinico - Vittorio Emanuele" (Presidio Ferrarotto Alessi); Recruiting

Catania, Italy, 90124

Contact: Site Contact +39953781994 gaegiuffrida@gmail.com

Principal Investigator: Gaetano Giuffrida

Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico; Active, not recruiting

Milano, Italy, 20122

Fondazione Policlinico Universitario Agostino Gemelli IRCCS; Completed

Roma, Italy, 168

Dipartimento di Medicina Traslazionale e di Precisione - "Sapienza" Universita di Roma; Recruiting

Rome, Italy, 00161

Contact: Site Contact chistolini@bce.uniroma1.it

Principal Investigator: Antonio Chistollini

Japan

Kyushu University Hospital; Completed

Fukuoka-shi, Fukuoka-Ken, Japan, 812-8582

Hyogo College of Medicine Hospital; Completed

Nishinomiya-shi, Hyogo-Ken, Japan, 663-8501

Medical Hospital, Tokyo Medical and Dental University; Completed

Bunkyo-ku, Tokyo-To, Japan, 113-8519

Poland

Samodzielny Publiczny Dzieciecy Szpital Kliniczny; Completed

Warszawa, Poland, 02-091

Instytut Hematologii i Transfuzjologii; Completed

Warszawa, Poland, 02-776

Spain

Complejo Hospitalario Universitario A Coruña; Recruiting

A Coruña, La Coruña, Spain, 15006

Contact: Site Contact 34981176668 Maria.fernada.lopez.fernandez@sergas.es

Principal Investigator: Maria Fernanda Lopez Fernandez

Hospital de Cruces; Completed

Barakaldo, Vizcaya, Spain, 48903

Hospital General Universitario de Alicante; Completed

Alicante, Spain, 3010

Hospital Universitario de Salamanca; Completed

Salamanca, Spain, 37007

Hospital Universitario Virgen del Rocio; Completed

Sevilla, Spain, 41013

Hospital Universitari i Politecnic La Fe; Recruiting

València, Spain, 46026

Contact: Site Contact +34961244865 sbonanad@gmail.com

Principal Investigator: Santiago Bonanad

Switzerland

Inselspital - Universitaetsspital Bern; Withdrawn

Bern, Switzerland, 3010

United Kingdom

University College London Hospitals; Completed

London, Greater London, United Kingdom, NW1 2PG

Royal Manchester Children's Hospital; Completed

Manchester, United Kingdom, M139WL

Sponsors and Collaborators

Baxalta now part of Shire

Takeda Development Center Americas, Inc.

Investigators

• Study Director: Study Director; Shire

More Information

Additional Information:

To obtain more information on the study, click here/on this link 

• Responsible Party: Baxalta now part of Shire
• ClinicalTrials.gov Identifier: NCT03393975
• Other Study ID Numbers: 281102; 2017-000858-18 ( EudraCT Number ); TAK-755-281102 ( Other Identifier: Sponsor )
• First Posted: January 9, 2018
• Last Update Posted: February 28, 2024
• Last Verified: February 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment 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 on https://vivli.org/ourmember/takeda/. 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://vivli.org/ourmember/takeda/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Purpura; Purpura, Thrombocytopenic; Purpura, Thrombotic Thrombocytopenic; Blood Coagulation Disorders; Hematologic Diseases; Hemorrhage; Pathologic Processes; Skin Manifestations; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Immune System Diseases; Thrombophilia