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

Thrombotic Thrombocytopenic Purpura (TTP) Clinical Trial

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])

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03393975
• Other study ID #: 281102
• Secondary ID: 2017-000858-18TA
• Status: Completed
• Phase: Phase 3
• Start date: October 13, 2017
• Est. completion date: May 30, 2024

Study information

• Verified date: June 2024
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: May 30, 2024
• Est. primary completion date: December 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Purpura
• Purpura, Thrombocytopenic
• Purpura, Thrombotic Thrombocytopenic
• Thrombotic Thrombocytopenic Purpura (TTP)

Intervention

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

Locations

Country	Name	City	State
Austria	AKH - Medizinische Universität Wien	Vienna
France	Hopital Claude Huriez - CHU Lille	Lille	Nord
France	Hôpital Robert Debré - Paris	Paris
France	Hôpital Saint-Antoine	Paris cedex 12	Paris
France	Hôpital Necker - Enfants Malades	Paris cedex 15	Paris
France	CHU Saint Etienne - Hôpital Nord	Saint-Priest-en-Jarez cedex	Loire
Germany	Universitaetsklinikum Hamburg-Eppendorf	Hamburg
Germany	Universitaetsklinikum Jena	Jena	Thueringen
Italy	Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)	Bergamo
Italy	Azienda Ospedaliera Universitaria "Policlinico - Vittorio Emanuele" (Presidio Ferrarotto Alessi)	Catania
Italy	Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico	Milano
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Roma
Italy	Dipartimento di Medicina Traslazionale e di Precisione - "Sapienza" Universita di Roma	Rome
Japan	Medical Hospital, Tokyo Medical and Dental University	Bunkyo-ku	Tokyo-To
Japan	Kyushu University Hospital	Fukuoka-shi	Fukuoka-Ken
Japan	Hyogo College of Medicine Hospital	Nishinomiya-shi	Hyogo-Ken
Poland	Instytut Hematologii i Transfuzjologii	Warszawa
Poland	Samodzielny Publiczny Dzieciecy Szpital Kliniczny	Warszawa
Spain	Complejo Hospitalario Universitario A Coruña	A Coruña	La Coruña
Spain	Hospital General Universitario de Alicante	Alicante
Spain	Hospital de Cruces	Barakaldo	Vizcaya
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital Universitari i Politecnic La Fe	València
United Kingdom	University College London Hospitals	London	Greater London
United Kingdom	Royal Manchester Children's Hospital	Manchester
United States	Winship Cancer Institute	Atlanta	Georgia
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Ohio State Univ College Of Medicine	Columbus	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	The Methodist Hospital	Houston	Texas
United States	Alliance for Childhood Diseases, Cure 4 the Kids Foundation	Las Vegas	Nevada
United States	University of Oklahoma	Oklahoma City	Oklahoma

Sponsors (2)

Lead Sponsor	Collaborator
Baxalta now part of Shire	Takeda Development Center Americas, Inc.

Countries where clinical trial is conducted

United States,  Austria,  France,  Germany,  Italy,  Japan,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Acute Thrombotic Thrombocytopenic Purpura (TTP) Events	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.	Throughout the study period of approximately 70 months
Secondary	Percentage of Acute Thrombotic Thrombocytopenic Purpura (TTP) Events Responding to BAX 930	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.	Throughout the study period of approximately 70 months
Secondary	Time to Resolution of Acute TTP Events	Time to resolution of acute TTP events following initiation of treatment with BAX 930 or SoC agent will be assessed.	Throughout the study period of approximately 70 months
Secondary	Number of Participants With Thrombocytopenia	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.	Throughout the study period of approximately 70 months
Secondary	Number of Participants With Microangiopathic Hemolytic Anemia	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.	Throughout the study period of approximately 70 months
Secondary	Number of Participants With Neurological symptoms	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.	Throughout the study period of approximately 70 months
Secondary	Number of Participants With Renal Dysfunction	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.	Throughout the study period of approximately 70 months
Secondary	Number of Participants With Abdominal Pain	Number of participants with abdominal pain (TTP related) will be reported by treatment arm for the prophylactic cohort.	Throughout the study period of approximately 70 months
Secondary	Number of Participants With Supplemental Doses	Number of participants with supplemental doses prompted by subacute TTP events will be reported by treatment for the prophylactic cohort.	Throughout the study period of approximately 70 months
Secondary	Number of Participants With Dose Modification	Number of participants with dose modification not prompted by an acute TTP event will be reported by treatment for the prophylactic cohort.	Throughout the study period of approximately 70 months
Secondary	Number of Participants With Acute Thrombotic Thrombocytopenic Purpura (TTP) Events on Their Final Dose	Number of participants with acute TTP events on their final dose and dosing regimen for the prophylactic cohort will be reported.	Throughout the study period of approximately 70 months
Secondary	Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)	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.	Throughout the study period of approximately 70 months
Secondary	Number of Participants With Antibodies to ADAMTS13	Number of participants with binding and inhibitory antibodies to ADAMTS13 will be reported.	Throughout the study period of approximately 70 months
Secondary	Estimated Total Quantity of ADAMTS13 Administered During the Treatment of Acute TTP Events	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.	Throughout the study period of approximately 70 months
Secondary	Incremental Recovery (IR) of ADMATS13 Activity and ADMATS13 Antigen for SoC Agent and BAX 930 in Plasma	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.	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
Secondary	Area Under the Plasma curve [AUC] of ADMATS13 Activity and ADMATS13 Antigen for SoC Agent and BAX 930 in Plasma	AUC of ADMATS13 activity and ADMATS13 antigen for SoC agent and BAX 930 in plasma will be reported.	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
Secondary	Terminal Half-Life (T1/2) of ADMATS13 Activity and ADMATS13 Antigen for SoC Agent and BAX 930 in Plasma	T1/2 of ADMATS13 activity and ADMATS13 antigen for SoC agent and BAX 930 in plasma will be reported.	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
Secondary	Mean Residence Time (MRT) of ADMATS13 Activity and ADMATS13 Antigen for SoC Agent and BAX 930 in Plasma	MRT of ADMATS13 activity and ADMATS13 antigen for SoC agent and BAX 930 in plasma will be reported.	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
Secondary	Clearance (CL) of ADMATS13 Activity and ADMATS13 Antigen for SoC Agent and BAX 930 in Plasma	CL of ADMATS13 activity and ADMATS13 antigen for SoC agent and BAX 930 in plasma will be reported.	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
Secondary	Volume at Steady State (Vss) of ADMATS13 Activity and ADMATS13 Antigen for SoC Agent and BAX 930 in Plasma	Vss of ADMATS13 activity and ADMATS13 antigen for SoC agent and BAX 930 in plasma will be reported.	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
Secondary	Maximum Concentration (Cmax) of ADMATS13 Activity and ADMATS13 Antigen for SoC Agent and BAX 930 in Plasma	Cmax of ADMATS13 activity and ADMATS13 antigen for SoC agent and BAX 930 in plasma will be reported.	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
Secondary	Assessment of Von Willebrand Factor: Antigen (VWF:Ag)	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.	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
Secondary	Assessment of Von Willebrand Factor: Ristocetin Cofactor Activity (VWF: RCo)	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.	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
Secondary	Assessment of ADAMTS13 Activity (Pre-Infusion ADAMTS13 Levels) and Select VWF Parameters	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.	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
Secondary	Assessment of Total Binding Antibodies to ADAMTS13	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.	Start of treatment periods 1, 2 and 3: within 60 min pre-infusion and at study completion/early termination visit (up to 19 months)
Secondary	Assessment of Neutralizing Antibodies to ADAMTS13	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.	Start of treatment periods 1, 2 and 3: within 60 min pre-infusion and at study completion/early termination visit (up to 19 months)
Secondary	Assessment of Anti-Chinese Hamster Ovary (Anti-CHO) Protein Antibodies	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.	Start of treatment periods 1, 2 and 3: within 60 min pre-infusion and at study completion/early termination visit (up to 19 months)
Secondary	Time to Onset of Immunogenic Response to ADAMTS13	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	Start of treatment periods 1, 2 and 3: within 60 min pre-infusion and at study completion/early termination visit (up to 19 months)
Secondary	Health Related Quality of Life (HRQoL): cTTP-Specific Patient reported outcomes (PROs)	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.	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)
Secondary	Health Related Quality of Life (HRQoL): 36-Item Short Form Health Survey (SF-36)	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.	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)
Secondary	Health Related Quality of Life (HRQoL): Abbreviated 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9)	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.	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)
Secondary	Health Related Quality of Life (HRQoL): EuroQol 5 Dimensions Questionnaire 3-Level (EQ-5D-3L)	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.	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)
Secondary	Health Related Quality of Life (HRQoL): EQ-5D-youth (EQ-5D-Y)	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.	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)
Secondary	Health Related Quality of Life (HRQoL): Pediatric Quality of Life Inventory (Ped QL)	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.	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)
Secondary	Resource Utilization: Length of Hospital Stay for Acute TTP Events	Number of days participants stay in hospital for Acute TTP events will be assessed.	Throughout the study period of approximately 70 months
Secondary	Resource Utilization: Resource Utilization During Prophylaxis	Number of participants utilized during prophylaxis will be assessed.	Throughout the study period of approximately 70 months
Secondary	Resource Utilization: Days Missed From School or Work due to TTP-Related Illness	Number of days missed from school or work due to TTP-related illness will be assessed.	Throughout the study period of approximately 70 months

External Links

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