Thrombotic Thrombocytopenic Purpura (TTP)
Conditions
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.
Interventions
BIOLOGICALTAK-755
Participants in prophylaxis cohort will receive IV infusions of 40 IU/kg TAK-755 ORT during Period 1 and Period 2 and switch to TAK-755 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 TAK-755.
BIOLOGICALStandard of care
Participants will receive Investigator-recommended Standard of care (SoC).
Sponsors
Baxalta now part of Shire
Takeda Development Center Americas, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
NONE
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).
Eligibility
Sex/Gender
ALL
Age
0 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Acute Thrombotic Thrombocytopenic Purpura (TTP) Events During Prophylactic Treatment | Up to 74.5 months | As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Acute Thrombotic Thrombocytopenic Purpura (TTP) Events Responding to TAK-755 | Up to 79.6 months | Percentage of acute TTP events responding to TAK-755, was defined as not requiring the use of another human disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13 (ADAMTS13)-containing agent. As per planned analysis, data for this outcome measure were collected and reported only for the TAK-755 treatment arm of both the prophylaxis (irrespective of the prophylaxis periods) and on demand cohorts. |
| Time to Resolution of Acute TTP Events | Up to 79.6 months | Time to resolution of acute TTP events following initiation of treatment with TAK-755 or SoC agent was assessed. Acute TPP events were considered resolved when: (a) Platelet count was \>150,000 per microliter (μL) or drop of platelet count was within 25 percent (%) of baseline, whichever occurred first, and (b) Elevation of lactate dehydrogenase (LDH) \<1.5 x baseline or \<1.5 x upper limit of normal (ULN). As per planned analysis, data for this outcome measure were collected and reported in a combined manner irrespective of the prophylaxis treatment Periods, partitioned per treatment received (TAK-755 and SoC) for the on demand and prophylactic cohorts. |
| Number of Participants With Thrombocytopenia During Prophylactic Treatment | Up to 79.6 months | Thrombocytopenia was defined as a decrease in platelet count ≥25 % of baseline or a platelet count \<150,000/μL, reported by treatment arm for the prophylactic cohort. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755. |
| Number of Participants With Microangiopathic Hemolytic Anemia During Prophylactic Treatment | Up to 79.6 months | Microangiopathic hemolytic anemia was defined as an elevation of LDH \>1.5\* of baseline or \>1.5\*ULN (with a possible evidence of schistocytes on blood smear) and was reported by treatment arm for the prophylactic cohort. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755. |
| Number of Participants With Neurological Symptoms During Prophylactic Treatment | Up to 79.6 months | Neurological symptoms (TTP related) (e.g., confusion, dysphonia, dysarthria, focal or general motor symptoms including seizures), were reported by treatment arm for the prophylactic cohort. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755. |
| Number of Participants With Renal Dysfunction During Prophylactic Treatment | Up to 79.6 months | Renal dysfunction was defined as an increase in serum creatinine \>1.5\*baseline. Number of participants with renal dysfunction were reported by treatment arm for the prophylactic cohort. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755. |
| Number of Participants With Abdominal Pain During Prophylactic Treatment | Up to 79.6 months | Number of participants with abdominal pain (TTP related) were reported by treatment arm for the prophylaxis cohort. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755. |
| Number of Supplemental Doses Prompted by Subacute TTP Event During Prophylactic Treatment | Up to 79.6 months | Number of supplemental doses prompted by subacute TTP events were reported by treatment for the prophylactic cohort. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755. |
| Number of Participants With Dose Modification Not Prompted by an Acute TTP Event During Prophylactic Treatment | Up to 79.6 months | Number of participants with dose modification not prompted by an acute TTP event were reported by treatment for the prophylactic cohort. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755. |
| Number of Participants With Acute TTP Events on Their Final Dose | Up to 79.6 months | Number of participants with acute TTP events on their final dose and dosing regimen for the prophylactic cohort were reported. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Treatment Emergent Adverse Events (Serious TEAEs) | Up to 79.6 months | AE: Any untoward medical occurrence in participants administered IP that does not necessarily have a causal relationship with treatment. TEAE: AE that has start date-time on/after start date-time of first dose of treatment participant is taking on that assessment/period or if it has start date-time before start date-time of first dose but increases in severity on/after start date-time of the first dose of treatment. SAE: An untoward medical occurrence that at any dose meets 1 or more of following criteria: death; initial/prolonged in-patient hospitalization; life threatening experience; persistent/significant disability/incapacity; congenital anomaly, medically important event (may not be immediately life threatening or result in death or require hospitalization but may require medical or surgical intervention to prevent 1 of the other outcomes). Vital signs, clinical chemistry, hematology as assessed by the investigator were reported as AE. |
| Number of Participants With Inhibitory Antibodies to ADAMTS13 | Up to 79.6 months | Number of participants with inhibitory antibodies to ADAMTS13 were reported. As per planned analysis, data for this outcome measure were collected and reported in a combined manner irrespective of the Prophylaxis Periods and partitioned as per the treatment received during the course of the study, presented for the prophylaxis cohorts only. |
| Total Quantity of ADAMTS13 Administered During the Treatment of Acute TTP Events in Participants in TAK-755 Treatment Arm | Up to 79.6 months | Total quantity of ADAMTS13 administered during the treatment of acute TTP events (all acute TTP events irrespective of central lab confirmation were included) was assessed. Acute TTP events typically require 3 to 4 days of intensified treatment. As per planned analysis, data for this outcome measure were collected and reported only for the TAK-755 treatment arm of both the prophylaxis (irrespective of the prophylaxis periods) and on demand cohorts. |
| Incremental Recovery (IR) of ADAMTS13 Activity for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I (Month 1:Day 1 up to 12), PK-II (Month 12:Day 1 up to 12), and PK-III (Month 19:Day 1 up to 12): Pre-infusion and at multiple timepoints post-infusion up to 288 hours | ADAMTS13 activity was measured by the fluorescent resonance energy transfer (FRETS) assay. IR was defined as body weight normalized maximum increase in plasma ADAMTS13 activity level. IR of ADAMTS13 activity for SoC agent and TAK-755 in plasma was assessed. (IU/mL)/(IU/kg) stands for (International units per milliliter)/(International units per kilogram). PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1, end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same. |
| Maximum Concentration (Cmax) of ADAMTS13 Activity for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I (Month 1:Day 1 up to 12), PK-II (Month 12:Day 1 up to 12), and PK-III (Month 19:Day 1 up to 12): Pre-infusion and at multiple timepoints post-infusion up to 288 hours | IU/mL stands for International units per milliliter. PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth,Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same. |
| IR of ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I (Month 1:Day 1 up to 12), PK-II (Month 12:Day 1 up to 12), and PK-III (Month 19:Day 1 up to 12): Pre-infusion and at multiple timepoints post-infusion up to 288 hours | ADAMTS13 antigen was measured using a commercial ADAMTS13 enzyme-linked immunosorbent assay (ELISA) employing ADAMTS13 antigen. IR was defined as body weight normalized maximum increase in plasma ADAMTS13 antigen. IR of ADAMTS13 antigen for SoC agent and TAK-755 in plasma was assessed. (µg/mL)/ (µg/kg) stands for (microgram per milliliter)/(microgram per kilogram). PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1, end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same. |
| Area Under the Plasma Curve [AUC]All of ADAMTS13 Activity for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I (Month 1:Day 1 up to 12), PK-II (Month 12:Day 1 up to 12), and PK-III (Month 19:Day 1 up to 12): Pre-infusion and at multiple timepoints post-infusion up to 288 hours | h\*IU/mL denotes for hours\*international units per milliliters. PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same. |
| AUCall of ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I (Month 1:Day 1 up to 12), PK-II (Month 12:Day 1 up to 12), and PK-III (Month 19:Day 1 up to 12): Pre-infusion and at multiple timepoints post-infusion up to 288 hours | h\*µg/mL denotes for hours\*microgram per milliliters. PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same. |
| Terminal Half-Life (t1/2) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I (Month 1:Day 1 up to 12), PK-II (Month 12:Day 1 up to 12), and PK-III (Month 19:Day 1 up to 12): Pre-infusion and at multiple timepoints post-infusion up to 288 hours | PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same. |
| Mean Residence Time Extrapolated to Infinity (MRT0-inf) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I (Month 1:Day 1 up to 12), PK-II (Month 12:Day 1 up to 12), and PK-III (Month 19:Day 1 up to 12): Pre-infusion and at multiple timepoints post-infusion up to 288 hours | PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same. |
| Clearance (CL) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I (Month 1:Day 1 up to 12), PK-II (Month 12:Day 1 up to 12), and PK-III (Month 19:Day 1 up to 12): Pre-infusion and at multiple timepoints post-infusion up to 288 hours | PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same. |
| Volume at Steady State (Vss) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I (Month 1:Day 1 up to 12), PK-II (Month 12:Day 1 up to 12), and PK-III (Month 19:Day 1 up to 12): Pre-infusion and at multiple timepoints post-infusion up to 288 hours | PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same. |
| Cmax of ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I (Month 1:Day 1 up to 12), PK-II (Month 12:Day 1 up to 12), and PK-III (Month 19:Day 1 up to 12): Pre-infusion and at multiple timepoints post-infusion up to 288 hours | µg/mL stands for microgram per milliliter. PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same. |
| Change From Baseline in Assessment of Von Willebrand Factor:Antigen (VWF:Ag) During Prophylactic Treatment | PK-I (Month 1:Day 12), PK-II (Month 12:Day 12), and PK-III (Month 19:Day 12): Post-infusion at 288 hours | VWF:Ag is a measure of total VWF protein and was 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 TAK-755 treatment during the initial PK assessment were reported. PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same. |
| Change From Baseline in Assessment of Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) During Prophylactic Treatment | PK-I (Month 1:Day 12), PK-II (Month 12:Day 12), and PK-III (Month 19:Day 12): Post-infusion at 288 hours | VWF:RCo provides 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 TAK-755 treatment during the initial PK assessment was reported. PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same. |
| Assessment of ADAMTS13 Activity Expressed as Pre-Infusion ADAMTS13 Levels | PK-I (Month 1:Day 1), PK-II (Month 12:Day 1), and PK-III (Month 19:Day 1): Pre-infusion (within 1 hour) | PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same. |
| Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:RCo | PK-I (Month 1:Day 1), PK-II (Month 12:Day 1), and PK-III (Month 19:Day 1): Pre-infusion (within 1 hour) | PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same. |
| Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:Ag | PK-I (Month 1:Day 1), PK-II (Month 12:Day 1), and PK-III (Month 19:Day 1): Pre-infusion (within 1 hour) | PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same. |
| Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:mm Low Resolution (Res.) Intermediate | PK-I (Month 1:Day 1), PK-II (Month 12:Day 1), and PK-III (Month 19:Day 1): Pre-infusion (within 1 hour) | PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same. |
| Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:mm Low Res. Large | PK-I (Month 1:Day 1), PK-II (Month 12:Day 1), and PK-III (Month 19:Day 1): Pre-infusion (within 1 hour) | PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same. |
| Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:mm Low Res. Small | PK-I (Month 1:Day 1), PK-II (Month 12:Day 1), and PK-III (Month 19:Day 1): Pre-infusion (within 1 hour) | PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same. |
| Number of Participants With Total Binding Antibodies to ADAMTS13 During Prophylactic Treatment | Up to 79.6 months | Total binding antibodies to ADAMTS13 were measured by an ELISA-based assay, detecting total immunoglobulins (IgG, IgA, and IgM). As per planned analysis, data for this outcome measure were collected and reported per sequence (Prophylaxis Cohort I: TAK-755 Then SoC and Prophylaxis Cohort II: SoC Then TAK-755) for the prophylaxis cohorts only. |
| Number of Participants With Neutralizing Antibodies to ADAMTS13 During Prophylactic Treatment | Up to 79.6 months | Neutralizing antibodies were measured by a Bethesda method with Nijmegen modification using the ADAMTS13 FRETS-VWF73 activity assay. As per planned analysis, data for this outcome measure were collected and reported per sequence (Prophylaxis Cohort I: TAK-755 Then SoC and Prophylaxis Cohort II: SoC Then TAK-755) for the prophylaxis cohorts only. |
| Number of Participants With Anti-Chinese Hamster Ovary (Anti-CHO) Protein Antibodies During Prophylactic Treatment | Up to 79.6 months | Total immunoglobulin antibodies (Immunoglobulin G \[IgG\], A \[IgA\], and M \[IgM\]) against CHO protein were analyzed using ELISA assay. As per planned analysis, data for this outcome measure were collected and reported per sequence (Prophylaxis Cohort I: TAK-755 Then SoC and Prophylaxis Cohort II: SoC Then TAK-755) for the prophylaxis cohorts only. |
| Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in cTTP-Patient Experience Questionnaire (cTTP-PEQ) Total Score | Baseline, Urgent Treatment Period: Day 7, End of Period 1 (Month 6), End of Period 2 (Month 12), and End of Period 3 (Month 19) | The cTTP-PEQ consists of 26 questions designed to assess the participant's experience of fatigue, joint, muscle, abdominal \&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 participant's attitudes, experienced side effects, work/school absences and travel impact associated with treatment received for TTP during the previous 2 weeks. The cTTP PEQ is focused on measuring the symptoms and impacts of disease. The total scores range from 0 to 162. A higher score indicates greater burden and poor quality of life. As per planned analysis,for the prophylaxis cohorts the data for this outcome measure were collected and reported by categorizing as per Prophylaxis Periods and per age groups,≥12 years,12 to 18 years,≥18 years for both on demand(OD) and prophylaxis cohorts. No participants in the OD Cohorts had cTTP-PEQ data available for analysis at scheduled post-baseline visits. |
| Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Physical and Mental Component Scores of the 36-Item Short Form Health Survey Version 2 (SF-36v2) | Baseline, Urgent Treatment Period: Day 7, End of Period 1 (Month 6), End of Period 2 (Month 12), and End of Period 3 (Month 19) | SF-36v2 is questionnaire that evaluated participant's health related quality of life. It included 36 questions related to 8 health dimensions: physical functioning, role-physical(role limitations due to physical health problems), bodily pain, general health, vitality(energy/fatigue),social functioning, role-emotional(role limitations due to emotional problems),\& mental health. Based on these 4 scales(physical functioning, role-physical, bodily pain, general health), physical component score was generated which ranges between 0 \&100, with higher scores indicating a better quality of life. Based on these 4 scales(vitality, social functioning, role-emotional,\&mental health), mental component score was generated ranging between 0\&100, with higher scores=better quality of life. As per planned analysis, for the prophylaxis cohorts data for this outcome measure were collected\&reported by categorizing as per Prophylaxis Periods and per component scores for both on demand\&prophylaxis cohorts. |
| Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Abbreviated 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) Domain Scores | Baseline, Urgent Treatment Period: Day 7, End of Period 1 (Month 6), End of Period 2 (Month 12), and End of Period 3 (Month 19) | TSQM is a treatment satisfaction measure 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 treatment 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 indicates greater satisfaction in that domain. As per planned analysis, for the prophylaxis cohorts data for this outcome measure were collected and reported by categorizing as per Prophylaxis Periods and per domain scores for both on demand and prophylaxis cohorts. |
| Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EuroQoL 5 Dimensions Questionnaire 3-Level (EQ-5D-3L) Domain Scores | Baseline, Urgent Treatment Period: Day 7, End of Period 1 (Month 6), End of Period 2 (Month 12), and End of Period 3 (Month 19) | EQ-5D-3L health questionnaire is a participant-answered questionnaire scoring 5 dimensions(domains) - mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is scored on an ordinal scale with 3 available levels of response and scores ranging from 1 to 3, "no problems," "some problems," and "extreme problems," respectively. Lower scores for the domains in the EQ-5D-3L indicate improvement. As per planned analysis, for the prophylaxis cohorts data for this outcome measure were collected and reported by categorizing as per Prophylaxis Periods and per domain scores for both on demand and prophylaxis cohorts. |
| Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EQ-5D-youth (EQ-5D-Y) Domain Scores | Baseline, Urgent Treatment Period: Day 7, End of Period 1 (Month 6), End of Period 2 (Month 12), and End of Period 3 (Month 19) | EQ-5D-Y health questionnaire is a participant answered questionnaire scoring 5 dimensions (domains) - mobility, self-care, usual activities, pain/discomfort and anxiety/depression assessed in participants aged from 8 to 16 years. The EQ-5D-Y descriptive system includes 5 descriptive items: Mobility, self-care, doing usual activities, having pain or discomfort, and feeling anxiety or depressed. Each dimension is scored at 3 levels: 1=No problems, 2=some problems, and 3=a lot of problems. Lower scores for the domains in the EQ-5D-Y indicate improvement. As per planned analysis, for the prophylaxis cohorts data for this outcome measure were collected and reported by categorizing as per Prophylaxis Periods and per domain scores for both on demand and prophylaxis cohorts. |
| Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Pediatric Quality of Life Inventory (Peds QL) Scale Total Scores | Baseline, Urgent Treatment Period: Day 7, End of Period 1 (Month 6), End of Period 2 (Month 12), and End of Period 3 (Month 19) | The PedsQL 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 consists 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. As per planned analysis, for the prophylaxis cohorts data for this outcome measure were collected and reported by categorizing as per Prophylaxis Periods and per age groups, 2 to \< 5 years, 5 to \< 8 years, 8 to \< 13 years, and 13 to \< 18 years, for both on demand and prophylaxis cohorts. |
| Resource Utilization: Annualized Length of Hospital Stay for Acute TTP Events for Prophylaxis Cohorts | Up to 79.6 months | The annualized number of days participants stayed in hospital for acute TTP events were assessed. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts in a combined manner for Periods 1 and 2 for SoC treatment and for Periods 1, 2, and 3 for TAK-755 treatment respectively. |
| Resource Utilization: Annualized Number of Acute Care Visits for Prophylaxis Cohorts | Up to 79.6 months | Annualized number of acute care visits was calculated as the number of acute care visits × 365.25/(End date - treatment start date + 1). As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts in a combined manner for Periods 1 and 2 for SoC treatment and for Periods 1, 2, and 3 for TAK-755 treatment respectively. |
| Resource Utilization: Annualized Number of Days Missed From School or Work for Prophylaxis Cohorts | Up to 79.6 months | Annualized number of days missed from school or work were assessed. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts in a combined manner for Periods 1 and 2 for SoC treatment and for Periods 1, 2, and 3 for TAK-755 treatment respectively. |
Countries
Austria, France, Germany, Italy, Japan, Poland, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORStudy Director
Shire
Participant flow
Recruitment details
Participants took part in the study at various investigative sites globally from 13 October 2017 to 30 May 2024.
Pre-assignment details
Participants with a diagnosis of severe congenital thrombotic thrombocytopenic purpura (cTTP) were enrolled in either prophylaxis or on demand cohorts. All participants received intravenous infusion of TAK-755 or standard treatment in Prophylaxis Periods 1 and 2, and TAK-755 in Prophylaxis Period 3 (hereafter Prophylaxis Periods 1, 2, and 3 are referred to simply as Periods 1, 2, and 3). 52 participants enrolled into the study but one participant withdrew before being randomized to treatment.
Participants by arm
| Arm | Count |
|---|---|
| Prophylaxis Cohort I: TAK-755 Then SoC Participants received a single IV infusion of 40 IU/kg TAK-755 ORT Q2W for 6 months in Period 1 followed by SoC for 6 months in Period 2. Thereafter participants received TAK-755 SIN dose IV infusion of 40 IU/kg Q2W for 6 months in Period 3. TAK-755 ORT could be replaced with TAK-755 SIN and vice versa depending on availability and other criteria. | 21 |
| Prophylaxis Cohort II: SoC Then TAK-755 Participants received SoC for 6 months in Period 1 followed by IV infusions of 40 IU/kg dose of TAK-755 ORT Q2W in Period 2 for the next 6 months. Thereafter participants received TAK-755 SIN dose IV infusions of 40 IU/kg Q2W for another 6 months in Period 3. TAK-755 ORT could be replaced with TAK-755 SIN and vice versa depending on availability and other criteria. | 27 |
| On Demand Cohort I: TAK-755 Participants experiencing an acute TTP event who met all other inclusion criteria and entered the study through the TAK-755 cohort of the Urgent Treatment Period received initial dose of IV infusions 40 IU/kg \[+/- 4 IU/kg\] TAK-755 ORT or TAK-755 SIN on Day 1 followed by a subsequent dose IV infusion of 20 IU/kg \[+/- 2 IU/kg\] TAK-755 ORT or TAK-755 SIN on Day 2 and an additional daily dose IV infusions of 15 IU/kg \[+/- 1.5 IU/kg\] TAK-755 on Day 3 until 2 days after the acute event was resolved. Upon resolution of the acute TTP event, participants had the option to either move to the prophylaxis cohort of the study or discontinue entirely. | 2 |
| On Demand Cohort II: SoC Participants experiencing an acute TTP event who met all other inclusion criteria and entered the study through the SoC cohort of the Urgent Treatment Period received the investigator-recommended SoC and dosing regimen until the acute event was resolved. Upon resolution of the acute TTP event, participants had the option to either move to the prophylaxis cohort of the study or discontinue entirely. | 4 |
| Total | 54 |
Baseline characteristics
| Characteristic | Prophylaxis Cohort I: TAK-755 Then SoC | Prophylaxis Cohort II: SoC Then TAK-755 | On Demand Cohort I: TAK-755 | On Demand Cohort II: SoC | Total |
|---|---|---|---|---|---|
| Age, Customized On Demand Cohort 12 to <18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized On Demand Cohort ≥18 years | 0 Participants | 0 Participants | 2 Participants | 3 Participants | 5 Participants |
| Age, Customized On Demand Cohort 6 to <12 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized On Demand Cohort <6 years | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Age, Customized Prophylaxis Cohort 12 to <18 years | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 4 Participants |
| Age, Customized Prophylaxis Cohort ≥18 years | 16 Participants | 20 Participants | 0 Participants | 0 Participants | 36 Participants |
| Age, Customized Prophylaxis Cohort 6 to <12 years | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 4 Participants |
| Age, Customized Prophylaxis Cohort <6 years | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 4 Participants |
| Ethnicity (NIH/OMB) On Demand Cohort Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) On Demand Cohort Not Hispanic or Latino | 0 Participants | 0 Participants | 2 Participants | 4 Participants | 6 Participants |
| Ethnicity (NIH/OMB) On Demand Cohort Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Prophylaxis Cohort Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Prophylaxis Cohort Not Hispanic or Latino | 16 Participants | 23 Participants | 0 Participants | 0 Participants | 39 Participants |
| Ethnicity (NIH/OMB) Prophylaxis Cohort Unknown or Not Reported | 4 Participants | 4 Participants | 0 Participants | 0 Participants | 8 Participants |
| Race (NIH/OMB) On Demand Cohort American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) On Demand Cohort Asian | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) On Demand Cohort Black or African American | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) On Demand Cohort More than one race | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) On Demand Cohort Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) On Demand Cohort Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) On Demand Cohort White | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Prophylaxis Cohort American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Prophylaxis Cohort Asian | 2 Participants | 3 Participants | 0 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) Prophylaxis Cohort Black or African American | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Prophylaxis Cohort More than one race | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Prophylaxis Cohort Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Prophylaxis Cohort Unknown or Not Reported | 4 Participants | 5 Participants | 0 Participants | 0 Participants | 9 Participants |
| Race (NIH/OMB) Prophylaxis Cohort White | 15 Participants | 17 Participants | 0 Participants | 0 Participants | 32 Participants |
| Sex: Female, Male On Demand Cohort Female | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male On Demand Cohort Male | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 4 Participants |
| Sex: Female, Male Prophylaxis Cohort Female | 12 Participants | 16 Participants | 0 Participants | 0 Participants | 28 Participants |
| Sex: Female, Male Prophylaxis Cohort Male | 9 Participants | 11 Participants | 0 Participants | 0 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 47 | 0 / 48 | 0 / 2 | 0 / 4 |
| other Total, other adverse events | 39 / 47 | 37 / 48 | 0 / 2 | 3 / 4 |
| serious Total, serious adverse events | 6 / 47 | 8 / 48 | 0 / 2 | 1 / 4 |
Outcome results
Primary
Number of Participants With Acute Thrombotic Thrombocytopenic Purpura (TTP) Events During Prophylactic Treatment
As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.
Time frame: Up to 74.5 months
Population: Modified Full Analysis Set (MFAS) included all FAS participants with the exclusion of those enrolled prior to November 2017 who were treated with SoC instead of the randomized treatment of TAK-755 in period 1 because TAK-755 was not available. For participants enrolled prior to November 2017, only the first 6 months of SoC treatment in period 1 was included in the analysis. Overall number of participants analyzed indicates the number of participants with data available for analyses.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Number of Participants With Acute Thrombotic Thrombocytopenic Purpura (TTP) Events During Prophylactic Treatment | 0 Participants |
| Prophylaxis Cohort: TAK-755 (Period 3) | Number of Participants With Acute Thrombotic Thrombocytopenic Purpura (TTP) Events During Prophylactic Treatment | 0 Participants |
| Prophylaxis Cohort: SoC (Periods 1 and 2) | Number of Participants With Acute Thrombotic Thrombocytopenic Purpura (TTP) Events During Prophylactic Treatment | 1 Participants |
Secondary
Area Under the Plasma Curve [AUC]All of ADAMTS13 Activity for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment
h\*IU/mL denotes for hours\*international units per milliliters. PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
Time frame: PK-I (Month 1:Day 1 up to 12), PK-II (Month 12:Day 1 up to 12), and PK-III (Month 19:Day 1 up to 12): Pre-infusion and at multiple timepoints post-infusion up to 288 hours
Population: The PK Analysis Set included all FAS participants who had adequate post-dose PK measurements for at least one of the PK analytes without major protocol deviations or events that may affect the integrity of the PK data. Overall number of participants analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses in the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Area Under the Plasma Curve [AUC]All of ADAMTS13 Activity for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I: ADAMTS13 Activity | 44.15 h*IU/mL | Standard Deviation 11.197 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Area Under the Plasma Curve [AUC]All of ADAMTS13 Activity for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-II: ADAMTS13 Activity | 52.83 h*IU/mL | Standard Deviation 11.94 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Area Under the Plasma Curve [AUC]All of ADAMTS13 Activity for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-II: ADAMTS13 Activity | 53.37 h*IU/mL | Standard Deviation 13.183 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Area Under the Plasma Curve [AUC]All of ADAMTS13 Activity for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-III: ADAMTS13 Activity | 62.69 h*IU/mL | Standard Deviation 26.763 |
| Prophylaxis Cohort: SoC (Periods 1 and 2) | Area Under the Plasma Curve [AUC]All of ADAMTS13 Activity for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I: ADAMTS13 Activity | 10.56 h*IU/mL | Standard Deviation 8.263 |
Secondary
Assessment of ADAMTS13 Activity Expressed as Pre-Infusion ADAMTS13 Levels
PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
Time frame: PK-I (Month 1:Day 1), PK-II (Month 12:Day 1), and PK-III (Month 19:Day 1): Pre-infusion (within 1 hour)
Population: The PD analysis set included all FAS participants who had at least one valid data point for at least one of the PD outcome measures and had no major protocol deviations or events that may affect the integrity of the PD data. Overall number of participants analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses in the specified category.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Assessment of ADAMTS13 Activity Expressed as Pre-Infusion ADAMTS13 Levels | ADAMTS13 Activity: PK-I | NA IU/mL |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Assessment of ADAMTS13 Activity Expressed as Pre-Infusion ADAMTS13 Levels | ADAMTS13 Activity: PK-II | NA IU/mL |
| Prophylaxis Cohort: TAK-755 (Period 3) | Assessment of ADAMTS13 Activity Expressed as Pre-Infusion ADAMTS13 Levels | ADAMTS13 Activity: PK-I | NA IU/mL |
| Prophylaxis Cohort: TAK-755 (Period 3) | Assessment of ADAMTS13 Activity Expressed as Pre-Infusion ADAMTS13 Levels | ADAMTS13 Activity: PK-II | NA IU/mL |
| Prophylaxis Cohort: TAK-755 (Period 3) | Assessment of ADAMTS13 Activity Expressed as Pre-Infusion ADAMTS13 Levels | ADAMTS13 Activity: PK-III | NA IU/mL |
| Prophylaxis Cohort: SoC (Periods 1 and 2) | Assessment of ADAMTS13 Activity Expressed as Pre-Infusion ADAMTS13 Levels | ADAMTS13 Activity: PK-I | NA IU/mL |
Secondary
Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:Ag
PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
Time frame: PK-I (Month 1:Day 1), PK-II (Month 12:Day 1), and PK-III (Month 19:Day 1): Pre-infusion (within 1 hour)
Population: The PD analysis set included all FAS participants who had at least one valid data point for at least one of the PD outcome measures and had no major protocol deviations or events that may affect the integrity of the PD data. Overall number of participants analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses in the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:Ag | PK-I: VWF:Ag | 110.38 percentage of VWF:Ag | Standard Deviation 45.205 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:Ag | PK-II: VWF:Ag | 120.48 percentage of VWF:Ag | Standard Deviation 49.224 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:Ag | PK-I: VWF:Ag | NA percentage of VWF:Ag | — |
| Prophylaxis Cohort: TAK-755 (Period 3) | Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:Ag | PK-II: VWF:Ag | 116.66 percentage of VWF:Ag | Standard Deviation 60.338 |
| Prophylaxis Cohort: SoC (Periods 1 and 2) | Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:Ag | PK-I: VWF:Ag | 105.07 percentage of VWF:Ag | Standard Deviation 40.539 |
Secondary
Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:mm Low Res. Large
PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
Time frame: PK-I (Month 1:Day 1), PK-II (Month 12:Day 1), and PK-III (Month 19:Day 1): Pre-infusion (within 1 hour)
Population: The PD analysis set included all FAS participants who had at least one valid data point for at least one of the PD outcome measures and had no major protocol deviations or events that may affect the integrity of the PD data. Overall number of participants analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses in the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:mm Low Res. Large | PK-I: VWF:mm Low Res. Large | 45.98 % of VWF:mm Low Res. Large | Standard Deviation 5.92 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:mm Low Res. Large | PK-II: VWF:mm Low Res. Large | 46.17 % of VWF:mm Low Res. Large | Standard Deviation 5.67 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:mm Low Res. Large | PK-I: VWF:mm Low Res. Large | NA % of VWF:mm Low Res. Large | — |
| Prophylaxis Cohort: TAK-755 (Period 3) | Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:mm Low Res. Large | PK-II: VWF:mm Low Res. Large | 44.93 % of VWF:mm Low Res. Large | Standard Deviation 7.319 |
| Prophylaxis Cohort: SoC (Periods 1 and 2) | Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:mm Low Res. Large | PK-I: VWF:mm Low Res. Large | 46.03 % of VWF:mm Low Res. Large | Standard Deviation 5.043 |
Secondary
Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:mm Low Resolution (Res.) Intermediate
PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
Time frame: PK-I (Month 1:Day 1), PK-II (Month 12:Day 1), and PK-III (Month 19:Day 1): Pre-infusion (within 1 hour)
Population: The PD analysis set included all FAS participants who had at least one valid data point for at least one of the PD outcome measures and had no major protocol deviations or events that may affect the integrity of the PD data. Overall number of participants analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses in the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:mm Low Resolution (Res.) Intermediate | PK-I: VWF:mm Low Res. Intermediate | 32.14 % of VWF:mm Low Res.Intermediate | Standard Deviation 3.375 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:mm Low Resolution (Res.) Intermediate | PK-II: VWF:mm Low Res. Intermediate | 30.87 % of VWF:mm Low Res.Intermediate | Standard Deviation 3.754 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:mm Low Resolution (Res.) Intermediate | PK-I: VWF:mm Low Res. Intermediate | NA % of VWF:mm Low Res.Intermediate | — |
| Prophylaxis Cohort: TAK-755 (Period 3) | Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:mm Low Resolution (Res.) Intermediate | PK-II: VWF:mm Low Res. Intermediate | 31.10 % of VWF:mm Low Res.Intermediate | Standard Deviation 3.616 |
| Prophylaxis Cohort: SoC (Periods 1 and 2) | Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:mm Low Resolution (Res.) Intermediate | PK-I: VWF:mm Low Res. Intermediate | 31.22 % of VWF:mm Low Res.Intermediate | Standard Deviation 2.955 |
Secondary
Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:mm Low Res. Small
PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
Time frame: PK-I (Month 1:Day 1), PK-II (Month 12:Day 1), and PK-III (Month 19:Day 1): Pre-infusion (within 1 hour)
Population: The PD analysis set included all FAS participants who had at least one valid data point for at least one of the PD outcome measures and had no major protocol deviations or events that may affect the integrity of the PD data. Overall number of participants analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses in the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:mm Low Res. Small | PK-I: VWF:mm Low Res. Small | 21.66 % of VWF:mm Low Res. Small | Standard Deviation 4.23 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:mm Low Res. Small | PK-II: VWF:mm Low Res. Small | 22.96 % of VWF:mm Low Res. Small | Standard Deviation 3.047 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:mm Low Res. Small | PK-I: VWF:mm Low Res. Small | NA % of VWF:mm Low Res. Small | — |
| Prophylaxis Cohort: TAK-755 (Period 3) | Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:mm Low Res. Small | PK-II: VWF:mm Low Res. Small | 23.96 % of VWF:mm Low Res. Small | Standard Deviation 5.32 |
| Prophylaxis Cohort: SoC (Periods 1 and 2) | Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:mm Low Res. Small | PK-I: VWF:mm Low Res. Small | 22.77 % of VWF:mm Low Res. Small | Standard Deviation 5.161 |
Secondary
Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:RCo
PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
Time frame: PK-I (Month 1:Day 1), PK-II (Month 12:Day 1), and PK-III (Month 19:Day 1): Pre-infusion (within 1 hour)
Population: The PD analysis set included all FAS participants who had at least one valid data point for at least one of the PD outcome measures and had no major protocol deviations or events that may affect the integrity of the PD data. Overall number of participants analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses in the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:RCo | PK-I: VWF:RCo | 145.54 percentage of VWF:RCo | Standard Deviation 54.698 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:RCo | PK-II: VWF:RCo | 155.76 percentage of VWF:RCo | Standard Deviation 63.032 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:RCo | PK-I: VWF:RCo | 137.62 percentage of VWF:RCo | Standard Deviation 52.978 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:RCo | PK-II: VWF:RCo | 154.98 percentage of VWF:RCo | Standard Deviation 74.444 |
| Prophylaxis Cohort: SoC (Periods 1 and 2) | Assessment of Select VWF Parameters Expressed as Pre-Infusion Levels of VWF:RCo | PK-I: VWF:RCo | 148.46 percentage of VWF:RCo | Standard Deviation 51.415 |
Secondary
AUCall of ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment
h\*µg/mL denotes for hours\*microgram per milliliters. PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
Time frame: PK-I (Month 1:Day 1 up to 12), PK-II (Month 12:Day 1 up to 12), and PK-III (Month 19:Day 1 up to 12): Pre-infusion and at multiple timepoints post-infusion up to 288 hours
Population: The PK Analysis Set included all FAS participants who had adequate post-dose PK measurements for at least one of the PK analytes without major protocol deviations or events that may affect the integrity of the PK data. Overall number of participants analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses in the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | AUCall of ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I: ADAMTS13 Antigen | 34.19 h*µg/mL | Standard Deviation 9.953 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | AUCall of ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-II: ADAMTS13 Antigen | 39.26 h*µg/mL | Standard Deviation 8.79 |
| Prophylaxis Cohort: TAK-755 (Period 3) | AUCall of ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-II: ADAMTS13 Antigen | 39.94 h*µg/mL | Standard Deviation 11.569 |
| Prophylaxis Cohort: TAK-755 (Period 3) | AUCall of ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-III: ADAMTS13 Antigen | 49.74 h*µg/mL | Standard Deviation 19.147 |
| Prophylaxis Cohort: SoC (Periods 1 and 2) | AUCall of ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I: ADAMTS13 Antigen | 6.899 h*µg/mL | Standard Deviation 4.779 |
Secondary
Change From Baseline in Assessment of Von Willebrand Factor:Antigen (VWF:Ag) During Prophylactic Treatment
VWF:Ag is a measure of total VWF protein and was 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 TAK-755 treatment during the initial PK assessment were reported. PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
Time frame: PK-I (Month 1:Day 12), PK-II (Month 12:Day 12), and PK-III (Month 19:Day 12): Post-infusion at 288 hours
Population: The Pharmacodynamic (PD) Analysis Set included all FAS participants who had at least one valid data point for at least one of the PD outcome measures and had no major protocol deviations or events that may affect the integrity of the PD data. Overall number of participants analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses in the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Change From Baseline in Assessment of Von Willebrand Factor:Antigen (VWF:Ag) During Prophylactic Treatment | VWF:Ag : PK-I | -0.11 percentage of VWF:Ag | Standard Deviation 17.064 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Change From Baseline in Assessment of Von Willebrand Factor:Antigen (VWF:Ag) During Prophylactic Treatment | VWF:Ag : PK-II | 0.48 percentage of VWF:Ag | Standard Deviation 34.798 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Change From Baseline in Assessment of Von Willebrand Factor:Antigen (VWF:Ag) During Prophylactic Treatment | VWF:Ag : PK-II | -1.31 percentage of VWF:Ag | Standard Deviation 22.259 |
| Prophylaxis Cohort: SoC (Periods 1 and 2) | Change From Baseline in Assessment of Von Willebrand Factor:Antigen (VWF:Ag) During Prophylactic Treatment | VWF:Ag : PK-I | 3.67 percentage of VWF:Ag | Standard Deviation 19.705 |
Secondary
Change From Baseline in Assessment of Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) During Prophylactic Treatment
VWF:RCo provides 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 TAK-755 treatment during the initial PK assessment was reported. PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
Time frame: PK-I (Month 1:Day 12), PK-II (Month 12:Day 12), and PK-III (Month 19:Day 12): Post-infusion at 288 hours
Population: The PD Analysis Set included all FAS participants who had at least one valid data point for at least one of the PD outcome measures and had no major protocol deviations or events that may affect the integrity of the PD data. Overall number of participants analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses in the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Change From Baseline in Assessment of Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) During Prophylactic Treatment | VWF:RCo- PK-I | 3.63 percentage of VWF:RCo | Standard Deviation 42.178 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Change From Baseline in Assessment of Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) During Prophylactic Treatment | VWF:RCo- PK-II | 7.45 percentage of VWF:RCo | Standard Deviation 31.917 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Change From Baseline in Assessment of Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) During Prophylactic Treatment | VWF:RCo- PK-II | 3.60 percentage of VWF:RCo | Standard Deviation 30.678 |
| Prophylaxis Cohort: SoC (Periods 1 and 2) | Change From Baseline in Assessment of Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) During Prophylactic Treatment | VWF:RCo- PK-I | 9.99 percentage of VWF:RCo | Standard Deviation 33.23 |
Secondary
Clearance (CL) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment
PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
Time frame: PK-I (Month 1:Day 1 up to 12), PK-II (Month 12:Day 1 up to 12), and PK-III (Month 19:Day 1 up to 12): Pre-infusion and at multiple timepoints post-infusion up to 288 hours
Population: The PK Analysis Set included all FAS participants who had adequate post-dose PK measurements for at least one of the PK analytes without major protocol deviations or events that may affect the integrity of the PK data. Overall number of participants analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses in the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Clearance (CL) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-II: ADAMTS13 Activity | 0.0530 liters per hour (L/h) | Standard Deviation 0.0134 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Clearance (CL) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I: ADAMTS13 Activity | 0.0618 liters per hour (L/h) | Standard Deviation 0.0143 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Clearance (CL) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I: ADAMTS13 Antigen | 0.0453 liters per hour (L/h) | Standard Deviation 0.0119 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Clearance (CL) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-II: ADAMTS13 Antigen | 0.0409 liters per hour (L/h) | Standard Deviation 0.0111 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Clearance (CL) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-III: ADAMTS13 Antigen | 0.0444 liters per hour (L/h) | Standard Deviation 0.0108 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Clearance (CL) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-II: ADAMTS13 Activity | 0.0553 liters per hour (L/h) | Standard Deviation 0.0115 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Clearance (CL) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-II: ADAMTS13 Antigen | 0.0480 liters per hour (L/h) | Standard Deviation 0.0133 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Clearance (CL) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-III: ADAMTS13 Activity | 0.0553 liters per hour (L/h) | Standard Deviation 0.0177 |
| Prophylaxis Cohort: SoC (Periods 1 and 2) | Clearance (CL) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I: ADAMTS13 Antigen | NA liters per hour (L/h) | — |
| Prophylaxis Cohort: SoC (Periods 1 and 2) | Clearance (CL) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I: ADAMTS13 Activity | NA liters per hour (L/h) | — |
Secondary
Cmax of ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment
µg/mL stands for microgram per milliliter. PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
Time frame: PK-I (Month 1:Day 1 up to 12), PK-II (Month 12:Day 1 up to 12), and PK-III (Month 19:Day 1 up to 12): Pre-infusion and at multiple timepoints post-infusion up to 288 hours
Population: The PK Analysis Set included all FAS participants who had adequate post-dose PK measurements for at least one of the PK analytes without major protocol deviations or events that may affect the integrity of the PK data. Overall number of participants analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses in the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Cmax of ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I: ADAMTS13 Antigen | 0.713 µg/mL | Standard Deviation 0.147 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Cmax of ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-II: ADAMTS13 Antigen | 0.807 µg/mL | Standard Deviation 0.188 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Cmax of ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I: ADAMTS13 Antigen | NA µg/mL | — |
| Prophylaxis Cohort: TAK-755 (Period 3) | Cmax of ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-II: ADAMTS13 Antigen | 0.844 µg/mL | Standard Deviation 0.168 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Cmax of ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-III: ADAMTS13 Antigen | 0.775 µg/mL | Standard Deviation 0.202 |
| Prophylaxis Cohort: SoC (Periods 1 and 2) | Cmax of ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I: ADAMTS13 Antigen | 0.134 µg/mL | Standard Deviation 0.0648 |
Secondary
Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Abbreviated 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) Domain Scores
TSQM is a treatment satisfaction measure 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 treatment 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 indicates greater satisfaction in that domain. As per planned analysis, for the prophylaxis cohorts data for this outcome measure were collected and reported by categorizing as per Prophylaxis Periods and per domain scores for both on demand and prophylaxis cohorts.
Time frame: Baseline, Urgent Treatment Period: Day 7, End of Period 1 (Month 6), End of Period 2 (Month 12), and End of Period 3 (Month 19)
Population: Modified FAS. Overall number of participants analyzed is the number of participants with data available for analyses. Number analyzed is the participants with data available for analyses for specified category. No participants in the OD Cohorts had TSQM-9 data available for analysis at scheduled post-baseline visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Abbreviated 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) Domain Scores | Global Satisfaction Score: End of Period 1 | 28.5714 score on a scale | Standard Deviation 9.03508 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Abbreviated 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) Domain Scores | Convenience Score: End of Period 2 | 27.2727 score on a scale | Standard Deviation 14.58363 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Abbreviated 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) Domain Scores | Treatment Effectiveness Score: End of Period 1 | 26.8519 score on a scale | Standard Deviation 36.07548 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Abbreviated 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) Domain Scores | Convenience Score: End of Period 3 | 21.3889 score on a scale | Standard Deviation 28.74204 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Abbreviated 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) Domain Scores | Global Satisfaction Score: End of Period 3 | 22.5000 score on a scale | Standard Deviation 15.76462 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Abbreviated 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) Domain Scores | Treatment Effectiveness Score: End of Period 2 | 23.2323 score on a scale | Standard Deviation 17.53624 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Abbreviated 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) Domain Scores | Global Satisfaction Score: End of Period 2 | 22.0779 score on a scale | Standard Deviation 16.73763 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Abbreviated 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) Domain Scores | Treatment Effectiveness Score: End of Period 3 | 21.6667 score on a scale | Standard Deviation 19.73673 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Abbreviated 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) Domain Scores | Convenience Score: End of Period 1 | 36.1111 score on a scale | Standard Deviation 16.759 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Abbreviated 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) Domain Scores | Convenience Score: End of Period 1 | 1.5152 score on a scale | Standard Deviation 10.85565 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Abbreviated 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) Domain Scores | Treatment Effectiveness Score: End of Period 1 | 3.5354 score on a scale | Standard Deviation 13.21072 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Abbreviated 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) Domain Scores | Treatment Effectiveness Score: End of Period 2 | 12.9630 score on a scale | Standard Deviation 17.0933 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Abbreviated 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) Domain Scores | Convenience Score: End of Period 2 | 14.8148 score on a scale | Standard Deviation 27.81479 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Abbreviated 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) Domain Scores | Global Satisfaction Score: End of Period 1 | 4.5455 score on a scale | Standard Deviation 16.0588 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Abbreviated 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) Domain Scores | Global Satisfaction Score: End of Period 2 | 14.2857 score on a scale | Standard Deviation 21.66536 |
| Unknown | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Abbreviated 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) Domain Scores | Global Satisfaction Score: Urgent Treatment Period Day 7 | — score on a scale | — |
| Unknown | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Abbreviated 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) Domain Scores | Treatment Effectiveness Score: Urgent Treatment Period Day 7 | — score on a scale | — |
| Unknown | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Abbreviated 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) Domain Scores | Convenience Score: Urgent Treatment Period Day 7 | — score on a scale | — |
Secondary
Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in cTTP-Patient Experience Questionnaire (cTTP-PEQ) Total Score
The cTTP-PEQ consists of 26 questions designed to assess the participant's experience of fatigue, joint, muscle, abdominal &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 participant's attitudes, experienced side effects, work/school absences and travel impact associated with treatment received for TTP during the previous 2 weeks. The cTTP PEQ is focused on measuring the symptoms and impacts of disease. The total scores range from 0 to 162. A higher score indicates greater burden and poor quality of life. As per planned analysis,for the prophylaxis cohorts the data for this outcome measure were collected and reported by categorizing as per Prophylaxis Periods and per age groups,≥12 years,12 to 18 years,≥18 years for both on demand(OD) and prophylaxis cohorts. No participants in the OD Cohorts had cTTP-PEQ data available for analysis at scheduled post-baseline visits.
Time frame: Baseline, Urgent Treatment Period: Day 7, End of Period 1 (Month 6), End of Period 2 (Month 12), and End of Period 3 (Month 19)
Population: Modified FAS:FAS participants with exclusion of those enrolled prior to Nov.2017 who were treated with SoC instead of randomized treatment of TAK-755 in period 1 because TAK-755 was not available. For participants enrolled prior to Nov. 2017,only first 6 months of SoC treatment in period 1 was included in analysis. Overall number of participants analyzed:number of participants with data available for analyses. Number analyzed:participants with data available for analyses for specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in cTTP-Patient Experience Questionnaire (cTTP-PEQ) Total Score | ≥18 years: Total Score, End of Period 1 | -2.6 score on a scale | Standard Deviation 24.17 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in cTTP-Patient Experience Questionnaire (cTTP-PEQ) Total Score | 12 to < 18 years: Total Score, End of Period 2 | 13.0 score on a scale | — |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in cTTP-Patient Experience Questionnaire (cTTP-PEQ) Total Score | 12 to < 18 years: Total Score, End of Period 3 | -6.0 score on a scale | — |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in cTTP-Patient Experience Questionnaire (cTTP-PEQ) Total Score | ≥12 years: Total Score, End of Period 1 | -2.6 score on a scale | Standard Deviation 24.17 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in cTTP-Patient Experience Questionnaire (cTTP-PEQ) Total Score | ≥18 years: Total Score, End of Period 3 | -10.2 score on a scale | Standard Deviation 13.42 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in cTTP-Patient Experience Questionnaire (cTTP-PEQ) Total Score | ≥12 years: Total Score, End of Period 2 | -9.4 score on a scale | Standard Deviation 17.75 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in cTTP-Patient Experience Questionnaire (cTTP-PEQ) Total Score | ≥18 years: Total Score, End of Period 2 | -11.3 score on a scale | Standard Deviation 17.16 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in cTTP-Patient Experience Questionnaire (cTTP-PEQ) Total Score | ≥12 years: Total Score, End of Period 3 | -10.0 score on a scale | Standard Deviation 13.14 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in cTTP-Patient Experience Questionnaire (cTTP-PEQ) Total Score | 12 to < 18 years: Total Score, End of Period 1 | 12.0 score on a scale | — |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in cTTP-Patient Experience Questionnaire (cTTP-PEQ) Total Score | ≥12 years: Total Score, End of Period 1 | -1.8 score on a scale | Standard Deviation 12 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in cTTP-Patient Experience Questionnaire (cTTP-PEQ) Total Score | ≥12 years: Total Score, End of Period 2 | -1.4 score on a scale | Standard Deviation 18.38 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in cTTP-Patient Experience Questionnaire (cTTP-PEQ) Total Score | ≥18 years: Total Score, End of Period 1 | -3.0 score on a scale | Standard Deviation 11.76 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in cTTP-Patient Experience Questionnaire (cTTP-PEQ) Total Score | ≥18 years: Total Score, End of Period 2 | -1.4 score on a scale | Standard Deviation 18.38 |
| Unknown | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in cTTP-Patient Experience Questionnaire (cTTP-PEQ) Total Score | ≥18 years: Total Score, Urgent Treatment Period Day 7 | — score on a scale | — |
| Unknown | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in cTTP-Patient Experience Questionnaire (cTTP-PEQ) Total Score | ≥12 years: Total Score, Urgent Treatment Period Day 7 | — score on a scale | — |
| Unknown | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in cTTP-Patient Experience Questionnaire (cTTP-PEQ) Total Score | 12 to < 18 years: Total Score, Urgent Treatment Period Day 7 | — score on a scale | — |
Secondary
Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EQ-5D-youth (EQ-5D-Y) Domain Scores
EQ-5D-Y health questionnaire is a participant answered questionnaire scoring 5 dimensions (domains) - mobility, self-care, usual activities, pain/discomfort and anxiety/depression assessed in participants aged from 8 to 16 years. The EQ-5D-Y descriptive system includes 5 descriptive items: Mobility, self-care, doing usual activities, having pain or discomfort, and feeling anxiety or depressed. Each dimension is scored at 3 levels: 1=No problems, 2=some problems, and 3=a lot of problems. Lower scores for the domains in the EQ-5D-Y indicate improvement. As per planned analysis, for the prophylaxis cohorts data for this outcome measure were collected and reported by categorizing as per Prophylaxis Periods and per domain scores for both on demand and prophylaxis cohorts.
Time frame: Baseline, Urgent Treatment Period: Day 7, End of Period 1 (Month 6), End of Period 2 (Month 12), and End of Period 3 (Month 19)
Population: Modified FAS. Overall number of participants analyzed is the number of participants with data available for analyses. Number analyzed is the participants with data available for analyses for specified category. No participants in the OD Cohorts had EQ-5D-Y data available for analysis at scheduled post-baseline visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EQ-5D-youth (EQ-5D-Y) Domain Scores | Anxiety/Depression: End of Period 3 | 0.0 score on a scale | Standard Deviation 0 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EQ-5D-youth (EQ-5D-Y) Domain Scores | Mobility: End of Period 1 | 0.0 score on a scale | — |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EQ-5D-youth (EQ-5D-Y) Domain Scores | Mobility: End of Period 2 | 0.0 score on a scale | Standard Deviation 0 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EQ-5D-youth (EQ-5D-Y) Domain Scores | Mobility: End of Period 3 | 0.0 score on a scale | Standard Deviation 0 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EQ-5D-youth (EQ-5D-Y) Domain Scores | Self-Care: End of Period 1 | 0.0 score on a scale | — |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EQ-5D-youth (EQ-5D-Y) Domain Scores | Self-Care: End of Period 2 | 0.0 score on a scale | Standard Deviation 0 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EQ-5D-youth (EQ-5D-Y) Domain Scores | Self-Care: End of Period 3 | 0.0 score on a scale | Standard Deviation 0 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EQ-5D-youth (EQ-5D-Y) Domain Scores | Usual Activities: End of Period 1 | 0.0 score on a scale | — |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EQ-5D-youth (EQ-5D-Y) Domain Scores | Usual Activities: End of Period 2 | 0.0 score on a scale | Standard Deviation 0 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EQ-5D-youth (EQ-5D-Y) Domain Scores | Usual Activities: End of Period 3 | 0.0 score on a scale | Standard Deviation 0 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EQ-5D-youth (EQ-5D-Y) Domain Scores | Pain/Discomfort: End of Period 1 | 1.0 score on a scale | — |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EQ-5D-youth (EQ-5D-Y) Domain Scores | Pain/Discomfort: End of Period 2 | -0.7 score on a scale | Standard Deviation 0.58 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EQ-5D-youth (EQ-5D-Y) Domain Scores | Pain/Discomfort: End of Period 3 | -0.3 score on a scale | Standard Deviation 0.96 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EQ-5D-youth (EQ-5D-Y) Domain Scores | Anxiety/Depression: End of Period 1 | 0.0 score on a scale | — |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EQ-5D-youth (EQ-5D-Y) Domain Scores | Anxiety/Depression: End of Period 2 | 0.3 score on a scale | Standard Deviation 0.58 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EQ-5D-youth (EQ-5D-Y) Domain Scores | Pain/Discomfort: End of Period 1 | -0.7 score on a scale | Standard Deviation 0.58 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EQ-5D-youth (EQ-5D-Y) Domain Scores | Usual Activities: End of Period 2 | 0.0 score on a scale | — |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EQ-5D-youth (EQ-5D-Y) Domain Scores | Self-Care: End of Period 1 | 0.0 score on a scale | Standard Deviation 0 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EQ-5D-youth (EQ-5D-Y) Domain Scores | Anxiety/Depression: End of Period 2 | 0.0 score on a scale | — |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EQ-5D-youth (EQ-5D-Y) Domain Scores | Self-Care: End of Period 2 | 0.0 score on a scale | — |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EQ-5D-youth (EQ-5D-Y) Domain Scores | Anxiety/Depression: End of Period 1 | 0.0 score on a scale | Standard Deviation 0 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EQ-5D-youth (EQ-5D-Y) Domain Scores | Usual Activities: End of Period 1 | 0.0 score on a scale | Standard Deviation 0 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EQ-5D-youth (EQ-5D-Y) Domain Scores | Mobility: End of Period 1 | 0.0 score on a scale | Standard Deviation 0 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EQ-5D-youth (EQ-5D-Y) Domain Scores | Pain/Discomfort: End of Period 2 | 0.0 score on a scale | — |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EQ-5D-youth (EQ-5D-Y) Domain Scores | Mobility: End of Period 2 | 0.0 score on a scale | — |
| Unknown | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EQ-5D-youth (EQ-5D-Y) Domain Scores | Self-Care: Urgent Treatment Period Day 7 | — score on a scale | — |
| Unknown | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EQ-5D-youth (EQ-5D-Y) Domain Scores | Usual Activities: Urgent Treatment Period Day 7 | — score on a scale | — |
| Unknown | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EQ-5D-youth (EQ-5D-Y) Domain Scores | Pain/Discomfort: Urgent Treatment Period Day 7 | — score on a scale | — |
| Unknown | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EQ-5D-youth (EQ-5D-Y) Domain Scores | Anxiety/Depression: Urgent Treatment Period Day 7 | — score on a scale | — |
| Unknown | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EQ-5D-youth (EQ-5D-Y) Domain Scores | Mobility: Urgent Treatment Period Day 7 | — score on a scale | — |
Secondary
Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EuroQoL 5 Dimensions Questionnaire 3-Level (EQ-5D-3L) Domain Scores
EQ-5D-3L health questionnaire is a participant-answered questionnaire scoring 5 dimensions(domains) - mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is scored on an ordinal scale with 3 available levels of response and scores ranging from 1 to 3, no problems, some problems, and extreme problems, respectively. Lower scores for the domains in the EQ-5D-3L indicate improvement. As per planned analysis, for the prophylaxis cohorts data for this outcome measure were collected and reported by categorizing as per Prophylaxis Periods and per domain scores for both on demand and prophylaxis cohorts.
Time frame: Baseline, Urgent Treatment Period: Day 7, End of Period 1 (Month 6), End of Period 2 (Month 12), and End of Period 3 (Month 19)
Population: Modified FAS. Overall number of participants analyzed is the number of participants with data available for analyses. Number analyzed is the participants with data available for analyses for specified category. No participants in the OD Cohorts had EQ-5D-3L data available for analysis at scheduled post-baseline visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EuroQoL 5 Dimensions Questionnaire 3-Level (EQ-5D-3L) Domain Scores | Anxiety/Depression: End of Period 3 | -0.1 score on a scale | Standard Deviation 0.45 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EuroQoL 5 Dimensions Questionnaire 3-Level (EQ-5D-3L) Domain Scores | Mobility: End of Period 1 | 0.3 score on a scale | Standard Deviation 0.46 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EuroQoL 5 Dimensions Questionnaire 3-Level (EQ-5D-3L) Domain Scores | Mobility: End of Period 2 | -0.1 score on a scale | Standard Deviation 0.29 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EuroQoL 5 Dimensions Questionnaire 3-Level (EQ-5D-3L) Domain Scores | Mobility: End of Period 3 | -0.1 score on a scale | Standard Deviation 0.22 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EuroQoL 5 Dimensions Questionnaire 3-Level (EQ-5D-3L) Domain Scores | Self-Care: End of Period 1 | 0.1 score on a scale | Standard Deviation 0.35 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EuroQoL 5 Dimensions Questionnaire 3-Level (EQ-5D-3L) Domain Scores | Self-Care: End of Period 2 | 0.0 score on a scale | Standard Deviation 0 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EuroQoL 5 Dimensions Questionnaire 3-Level (EQ-5D-3L) Domain Scores | Self-Care: End of Period 3 | -0.1 score on a scale | Standard Deviation 0.22 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EuroQoL 5 Dimensions Questionnaire 3-Level (EQ-5D-3L) Domain Scores | Usual Activities: End of Period 1 | 0.0 score on a scale | Standard Deviation 0.53 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EuroQoL 5 Dimensions Questionnaire 3-Level (EQ-5D-3L) Domain Scores | Usual Activities: End of Period 2 | 0.0 score on a scale | Standard Deviation 0.43 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EuroQoL 5 Dimensions Questionnaire 3-Level (EQ-5D-3L) Domain Scores | Usual Activities: End of Period 3 | -0.1 score on a scale | Standard Deviation 0.39 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EuroQoL 5 Dimensions Questionnaire 3-Level (EQ-5D-3L) Domain Scores | Pain/Discomfort: End of Period 1 | 0.3 score on a scale | Standard Deviation 0.46 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EuroQoL 5 Dimensions Questionnaire 3-Level (EQ-5D-3L) Domain Scores | Pain/Discomfort: End of Period 2 | -0.3 score on a scale | Standard Deviation 0.62 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EuroQoL 5 Dimensions Questionnaire 3-Level (EQ-5D-3L) Domain Scores | Pain/Discomfort: End of Period 3 | -0.2 score on a scale | Standard Deviation 0.59 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EuroQoL 5 Dimensions Questionnaire 3-Level (EQ-5D-3L) Domain Scores | Anxiety/Depression: End of Period 1 | 0.1 score on a scale | Standard Deviation 0.64 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EuroQoL 5 Dimensions Questionnaire 3-Level (EQ-5D-3L) Domain Scores | Anxiety/Depression: End of Period 2 | -0.1 score on a scale | Standard Deviation 0.29 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EuroQoL 5 Dimensions Questionnaire 3-Level (EQ-5D-3L) Domain Scores | Self-Care: End of Period 2 | 0.0 score on a scale | Standard Deviation 0 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EuroQoL 5 Dimensions Questionnaire 3-Level (EQ-5D-3L) Domain Scores | Mobility: End of Period 2 | 0.0 score on a scale | Standard Deviation 0 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EuroQoL 5 Dimensions Questionnaire 3-Level (EQ-5D-3L) Domain Scores | Usual Activities: End of Period 2 | 0.0 score on a scale | Standard Deviation 0.63 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EuroQoL 5 Dimensions Questionnaire 3-Level (EQ-5D-3L) Domain Scores | Self-Care: End of Period 1 | 0.0 score on a scale | Standard Deviation 0 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EuroQoL 5 Dimensions Questionnaire 3-Level (EQ-5D-3L) Domain Scores | Pain/Discomfort: End of Period 2 | 0.2 score on a scale | Standard Deviation 0.41 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EuroQoL 5 Dimensions Questionnaire 3-Level (EQ-5D-3L) Domain Scores | Anxiety/Depression: End of Period 1 | 0.0 score on a scale | Standard Deviation 0 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EuroQoL 5 Dimensions Questionnaire 3-Level (EQ-5D-3L) Domain Scores | Anxiety/Depression: End of Period 2 | 0.0 score on a scale | Standard Deviation 0 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EuroQoL 5 Dimensions Questionnaire 3-Level (EQ-5D-3L) Domain Scores | Pain/Discomfort: End of Period 1 | -0.1 score on a scale | Standard Deviation 0.7 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EuroQoL 5 Dimensions Questionnaire 3-Level (EQ-5D-3L) Domain Scores | Mobility: End of Period 1 | -0.1 score on a scale | Standard Deviation 0.3 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EuroQoL 5 Dimensions Questionnaire 3-Level (EQ-5D-3L) Domain Scores | Usual Activities: End of Period 1 | -0.2 score on a scale | Standard Deviation 0.4 |
| Unknown | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EuroQoL 5 Dimensions Questionnaire 3-Level (EQ-5D-3L) Domain Scores | Self-Care: Urgent Treatment Period Day 7 | — score on a scale | — |
| Unknown | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EuroQoL 5 Dimensions Questionnaire 3-Level (EQ-5D-3L) Domain Scores | Usual Activities: Urgent Treatment Period Day 7 | — score on a scale | — |
| Unknown | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EuroQoL 5 Dimensions Questionnaire 3-Level (EQ-5D-3L) Domain Scores | Pain/Discomfort: Urgent Treatment Period Day 7 | — score on a scale | — |
| Unknown | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EuroQoL 5 Dimensions Questionnaire 3-Level (EQ-5D-3L) Domain Scores | Anxiety/Depression: Urgent Treatment Period Day 7 | — score on a scale | — |
| Unknown | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in EuroQoL 5 Dimensions Questionnaire 3-Level (EQ-5D-3L) Domain Scores | Mobility: Urgent Treatment Period Day 7 | — score on a scale | — |
Secondary
Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Pediatric Quality of Life Inventory (Peds QL) Scale Total Scores
The PedsQL 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 consists 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. As per planned analysis, for the prophylaxis cohorts data for this outcome measure were collected and reported by categorizing as per Prophylaxis Periods and per age groups, 2 to \< 5 years, 5 to \< 8 years, 8 to \< 13 years, and 13 to \< 18 years, for both on demand and prophylaxis cohorts.
Time frame: Baseline, Urgent Treatment Period: Day 7, End of Period 1 (Month 6), End of Period 2 (Month 12), and End of Period 3 (Month 19)
Population: Modified FAS. Overall number of participants analyzed is the number of participants with data available for analyses. Number analyzed is the participants with data available for analyses for specified category. No participants in the OD Cohorts had Peds QL data available for analysis at scheduled post-baseline visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Pediatric Quality of Life Inventory (Peds QL) Scale Total Scores | 8 to < 13 years, End of Period 3 | 5.7971 score on a scale | Standard Deviation 7.39876 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Pediatric Quality of Life Inventory (Peds QL) Scale Total Scores | 2 to < 5 years, End of Period 1 | 25.0000 score on a scale | Standard Deviation 47.14045 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Pediatric Quality of Life Inventory (Peds QL) Scale Total Scores | 2 to < 5 years, End of Period 3 | 24.4048 score on a scale | Standard Deviation 49.66583 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Pediatric Quality of Life Inventory (Peds QL) Scale Total Scores | 5 to < 8 years, End of Period 1 | 29.3478 score on a scale | — |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Pediatric Quality of Life Inventory (Peds QL) Scale Total Scores | 5 to < 8 years, End of Period 2 | -6.5217 score on a scale | — |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Pediatric Quality of Life Inventory (Peds QL) Scale Total Scores | 5 to < 8 years, End of Period 3 | 17.9348 score on a scale | Standard Deviation 19.21486 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Pediatric Quality of Life Inventory (Peds QL) Scale Total Scores | 8 to < 13 years, End of Period 1 | -2.1739 score on a scale | — |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Pediatric Quality of Life Inventory (Peds QL) Scale Total Scores | 8 to < 13 years, End of Period 2 | 8.6957 score on a scale | Standard Deviation 23.05783 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Pediatric Quality of Life Inventory (Peds QL) Scale Total Scores | 2 to < 5 years, End of Period 2 | 27.3810 score on a scale | Standard Deviation 47.14045 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Pediatric Quality of Life Inventory (Peds QL) Scale Total Scores | 8 to < 13 years, End of Period 2 | 1.0870 score on a scale | — |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Pediatric Quality of Life Inventory (Peds QL) Scale Total Scores | 5 to < 8 years, End of Period 1 | -16.3043 score on a scale | — |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Pediatric Quality of Life Inventory (Peds QL) Scale Total Scores | 8 to < 13 years, End of Period 1 | 15.2174 score on a scale | Standard Deviation 13.8347 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Pediatric Quality of Life Inventory (Peds QL) Scale Total Scores | 5 to < 8 years, End of Period 2 | 32.6087 score on a scale | — |
| Unknown | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Pediatric Quality of Life Inventory (Peds QL) Scale Total Scores | 5 to < 8 years: Urgent Treatment Period Day 7 | — score on a scale | — |
| Unknown | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Pediatric Quality of Life Inventory (Peds QL) Scale Total Scores | 8 to < 13 years: Urgent Treatment Period Day 7 | — score on a scale | — |
| Unknown | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Pediatric Quality of Life Inventory (Peds QL) Scale Total Scores | 13 to < 18 years: Urgent Treatment Period Day 7 | — score on a scale | — |
| Unknown | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Pediatric Quality of Life Inventory (Peds QL) Scale Total Scores | 2 to < 5 years: Urgent Treatment Period Day 7 | — score on a scale | — |
| Unknown | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Pediatric Quality of Life Inventory (Peds QL) Scale Total Scores | 13 to < 18 years, End of Period 1 | — score on a scale | — |
| Unknown | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Pediatric Quality of Life Inventory (Peds QL) Scale Total Scores | 13 to < 18 years, End of Period 2 | — score on a scale | — |
| Unknown | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Pediatric Quality of Life Inventory (Peds QL) Scale Total Scores | 13 to < 18 years, End of Period 3 | — score on a scale | — |
Secondary
Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Physical and Mental Component Scores of the 36-Item Short Form Health Survey Version 2 (SF-36v2)
SF-36v2 is questionnaire that evaluated participant's health related quality of life. It included 36 questions related to 8 health dimensions: physical functioning, role-physical(role limitations due to physical health problems), bodily pain, general health, vitality(energy/fatigue),social functioning, role-emotional(role limitations due to emotional problems),& mental health. Based on these 4 scales(physical functioning, role-physical, bodily pain, general health), physical component score was generated which ranges between 0 &100, with higher scores indicating a better quality of life. Based on these 4 scales(vitality, social functioning, role-emotional,&mental health), mental component score was generated ranging between 0&100, with higher scores=better quality of life. As per planned analysis, for the prophylaxis cohorts data for this outcome measure were collected&reported by categorizing as per Prophylaxis Periods and per component scores for both on demand&prophylaxis cohorts.
Time frame: Baseline, Urgent Treatment Period: Day 7, End of Period 1 (Month 6), End of Period 2 (Month 12), and End of Period 3 (Month 19)
Population: Modified FAS. Overall number of participants analyzed is the number of participants with data available for analyses. Number analyzed is the participants with data available for analyses for specified category. No participants in the OD Cohorts had SF-36v2 data available for analysis at scheduled post-baseline visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Physical and Mental Component Scores of the 36-Item Short Form Health Survey Version 2 (SF-36v2) | Mental Component Score: End of Period 3 | 3.766 score on a scale | Standard Deviation 7.2392 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Physical and Mental Component Scores of the 36-Item Short Form Health Survey Version 2 (SF-36v2) | Physical Component Score: End of Period 1 | 3.934 score on a scale | Standard Deviation 10.1098 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Physical and Mental Component Scores of the 36-Item Short Form Health Survey Version 2 (SF-36v2) | Physical Component Score: End of Period 2 | 3.112 score on a scale | Standard Deviation 6.0506 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Physical and Mental Component Scores of the 36-Item Short Form Health Survey Version 2 (SF-36v2) | Physical Component Score: End of Period 3 | 0.715 score on a scale | Standard Deviation 4.9878 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Physical and Mental Component Scores of the 36-Item Short Form Health Survey Version 2 (SF-36v2) | Mental Component Score: End of Period 1 | -7.263 score on a scale | Standard Deviation 7.4244 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Physical and Mental Component Scores of the 36-Item Short Form Health Survey Version 2 (SF-36v2) | Mental Component Score: End of Period 2 | 1.481 score on a scale | Standard Deviation 7.1315 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Physical and Mental Component Scores of the 36-Item Short Form Health Survey Version 2 (SF-36v2) | Mental Component Score: End of Period 2 | -4.853 score on a scale | Standard Deviation 9.9302 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Physical and Mental Component Scores of the 36-Item Short Form Health Survey Version 2 (SF-36v2) | Physical Component Score: End of Period 1 | -0.197 score on a scale | Standard Deviation 5.2511 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Physical and Mental Component Scores of the 36-Item Short Form Health Survey Version 2 (SF-36v2) | Mental Component Score: End of Period 1 | 5.001 score on a scale | Standard Deviation 5.0039 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Physical and Mental Component Scores of the 36-Item Short Form Health Survey Version 2 (SF-36v2) | Physical Component Score: End of Period 2 | 2.625 score on a scale | Standard Deviation 6.4219 |
| Unknown | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Physical and Mental Component Scores of the 36-Item Short Form Health Survey Version 2 (SF-36v2) | Physical Component Score: Urgent Treatment Period Day 7 | — score on a scale | — |
| Unknown | Health Related Quality of Life (HRQoL) Assessed as Change From Baseline in Physical and Mental Component Scores of the 36-Item Short Form Health Survey Version 2 (SF-36v2) | Mental Component Score: Urgent Treatment Period Day 7 | — score on a scale | — |
Secondary
Incremental Recovery (IR) of ADAMTS13 Activity for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment
ADAMTS13 activity was measured by the fluorescent resonance energy transfer (FRETS) assay. IR was defined as body weight normalized maximum increase in plasma ADAMTS13 activity level. IR of ADAMTS13 activity for SoC agent and TAK-755 in plasma was assessed. (IU/mL)/(IU/kg) stands for (International units per milliliter)/(International units per kilogram). PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1, end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
Time frame: PK-I (Month 1:Day 1 up to 12), PK-II (Month 12:Day 1 up to 12), and PK-III (Month 19:Day 1 up to 12): Pre-infusion and at multiple timepoints post-infusion up to 288 hours
Population: The PK Analysis Set included all FAS participants who had adequate post-dose PK measurements for at least one of the PK analytes without major protocol deviations or events that may affect the integrity of the PK data. Overall number of participants analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses in the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Incremental Recovery (IR) of ADAMTS13 Activity for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I: ADAMTS13 Activity | 0.025 (IU/mL)/(IU/kg) | Standard Deviation 0.00592 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Incremental Recovery (IR) of ADAMTS13 Activity for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-II: ADAMTS13 Activity | 0.0283 (IU/mL)/(IU/kg) | Standard Deviation 0.00644 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Incremental Recovery (IR) of ADAMTS13 Activity for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I: ADAMTS13 Activity | NA (IU/mL)/(IU/kg) | — |
| Prophylaxis Cohort: TAK-755 (Period 3) | Incremental Recovery (IR) of ADAMTS13 Activity for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-II: ADAMTS13 Activity | 0.0292 (IU/mL)/(IU/kg) | Standard Deviation 0.00611 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Incremental Recovery (IR) of ADAMTS13 Activity for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-III: ADAMTS13 Activity | 0.0279 (IU/mL)/(IU/kg) | Standard Deviation 0.00649 |
| Prophylaxis Cohort: SoC (Periods 1 and 2) | Incremental Recovery (IR) of ADAMTS13 Activity for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I: ADAMTS13 Activity | 0.0212 (IU/mL)/(IU/kg) | Standard Deviation 0.0267 |
Secondary
IR of ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment
ADAMTS13 antigen was measured using a commercial ADAMTS13 enzyme-linked immunosorbent assay (ELISA) employing ADAMTS13 antigen. IR was defined as body weight normalized maximum increase in plasma ADAMTS13 antigen. IR of ADAMTS13 antigen for SoC agent and TAK-755 in plasma was assessed. (µg/mL)/ (µg/kg) stands for (microgram per milliliter)/(microgram per kilogram). PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1, end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
Time frame: PK-I (Month 1:Day 1 up to 12), PK-II (Month 12:Day 1 up to 12), and PK-III (Month 19:Day 1 up to 12): Pre-infusion and at multiple timepoints post-infusion up to 288 hours
Population: The PK Analysis Set included all FAS participants who had adequate post-dose PK measurements for at least one of the PK analytes without major protocol deviations or events that may affect the integrity of the PK data. Overall number of participants analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses in the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | IR of ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I: ADAMTS13 Antigen | 0.0300 (µg/mL)/ (µg/kg) | Standard Deviation 0.00636 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | IR of ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-II: ADAMTS13 Antigen | 0.0327 (µg/mL)/ (µg/kg) | Standard Deviation 0.0105 |
| Prophylaxis Cohort: TAK-755 (Period 3) | IR of ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I: ADAMTS13 Antigen | NA (µg/mL)/ (µg/kg) | — |
| Prophylaxis Cohort: TAK-755 (Period 3) | IR of ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-II: ADAMTS13 Antigen | 0.0324 (µg/mL)/ (µg/kg) | Standard Deviation 0.00666 |
| Prophylaxis Cohort: TAK-755 (Period 3) | IR of ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-III: ADAMTS13 Antigen | 0.0299 (µg/mL)/ (µg/kg) | Standard Deviation 0.0073 |
| Prophylaxis Cohort: SoC (Periods 1 and 2) | IR of ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I: ADAMTS13 Antigen | 0.0187 (µg/mL)/ (µg/kg) | Standard Deviation 0.00619 |
Secondary
Maximum Concentration (Cmax) of ADAMTS13 Activity for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment
IU/mL stands for International units per milliliter. PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth,Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
Time frame: PK-I (Month 1:Day 1 up to 12), PK-II (Month 12:Day 1 up to 12), and PK-III (Month 19:Day 1 up to 12): Pre-infusion and at multiple timepoints post-infusion up to 288 hours
Population: The PK Analysis Set included all FAS participants who had adequate post-dose PK measurements for at least one of the PK analytes without major protocol deviations or events that may affect the integrity of the PK data. Overall number of participants analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses in the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Maximum Concentration (Cmax) of ADAMTS13 Activity for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I: ADAMTS13 Activity | 1.003 IU/mL | Standard Deviation 0.235 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Maximum Concentration (Cmax) of ADAMTS13 Activity for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-II: ADAMTS13 Activity | 1.130 IU/mL | Standard Deviation 0.253 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Maximum Concentration (Cmax) of ADAMTS13 Activity for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I: ADAMTS13 Activity | NA IU/mL | — |
| Prophylaxis Cohort: TAK-755 (Period 3) | Maximum Concentration (Cmax) of ADAMTS13 Activity for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-II: ADAMTS13 Activity | 1.167 IU/mL | Standard Deviation 0.246 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Maximum Concentration (Cmax) of ADAMTS13 Activity for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-III: ADAMTS13 Activity | 1.114 IU/mL | Standard Deviation 0.263 |
| Prophylaxis Cohort: SoC (Periods 1 and 2) | Maximum Concentration (Cmax) of ADAMTS13 Activity for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I: ADAMTS13 Activity | 0.192 IU/mL | Standard Deviation 0.102 |
Secondary
Mean Residence Time Extrapolated to Infinity (MRT0-inf) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment
PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
Time frame: PK-I (Month 1:Day 1 up to 12), PK-II (Month 12:Day 1 up to 12), and PK-III (Month 19:Day 1 up to 12): Pre-infusion and at multiple timepoints post-infusion up to 288 hours
Population: The PK Analysis Set included all FAS participants who had adequate post-dose PK measurements for at least one of the PK analytes without major protocol deviations or events that may affect the integrity of the PK data. Overall number of participants analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses in the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Mean Residence Time Extrapolated to Infinity (MRT0-inf) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-II: ADAMTS13 Activity | 65.89 hours | Standard Deviation 13.472 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Mean Residence Time Extrapolated to Infinity (MRT0-inf) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I: ADAMTS13 Activity | 64.35 hours | Standard Deviation 17.498 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Mean Residence Time Extrapolated to Infinity (MRT0-inf) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I: ADAMTS13 Antigen | 71.20 hours | Standard Deviation 16.538 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Mean Residence Time Extrapolated to Infinity (MRT0-inf) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-II: ADAMTS13 Antigen | 72.03 hours | Standard Deviation 19.611 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Mean Residence Time Extrapolated to Infinity (MRT0-inf) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-III: ADAMTS13 Antigen | 48.63 hours | Standard Deviation 6.867 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Mean Residence Time Extrapolated to Infinity (MRT0-inf) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-II: ADAMTS13 Activity | 61.46 hours | Standard Deviation 11.488 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Mean Residence Time Extrapolated to Infinity (MRT0-inf) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-II: ADAMTS13 Antigen | 66.30 hours | Standard Deviation 18.738 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Mean Residence Time Extrapolated to Infinity (MRT0-inf) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-III: ADAMTS13 Activity | 41.67 hours | Standard Deviation 6.171 |
| Prophylaxis Cohort: SoC (Periods 1 and 2) | Mean Residence Time Extrapolated to Infinity (MRT0-inf) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I: ADAMTS13 Antigen | NA hours | — |
| Prophylaxis Cohort: SoC (Periods 1 and 2) | Mean Residence Time Extrapolated to Infinity (MRT0-inf) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I: ADAMTS13 Activity | NA hours | — |
Secondary
Number of Participants With Abdominal Pain During Prophylactic Treatment
Number of participants with abdominal pain (TTP related) were reported by treatment arm for the prophylaxis cohort. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.
Time frame: Up to 79.6 months
Population: Modified FAS included all FAS participants with the exclusion of those enrolled prior to November 2017 who were treated with SoC instead of the randomized treatment of TAK-755 in period 1 because TAK-755 was not available. For participants enrolled prior to November 2017, only the first 6 months of SoC treatment in period 1 was included in the analysis. Overall number of participants analyzed indicates the number of participants with data available for analyses.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Number of Participants With Abdominal Pain During Prophylactic Treatment | 2 Participants |
| Prophylaxis Cohort: TAK-755 (Period 3) | Number of Participants With Abdominal Pain During Prophylactic Treatment | 2 Participants |
| Prophylaxis Cohort: SoC (Periods 1 and 2) | Number of Participants With Abdominal Pain During Prophylactic Treatment | 6 Participants |
Secondary
Number of Participants With Acute TTP Events on Their Final Dose
Number of participants with acute TTP events on their final dose and dosing regimen for the prophylactic cohort were reported. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.
Time frame: Up to 79.6 months
Population: Modified FAS included all FAS participants with the exclusion of those enrolled prior to November 2017 who were treated with SoC instead of the randomized treatment of TAK-755 in period 1 because TAK-755 was not available. For participants enrolled prior to November 2017, only the first 6 months of SoC treatment in period 1 was included in the analysis. Overall number of participants analyzed indicates the number of participants with data available for analyses.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Number of Participants With Acute TTP Events on Their Final Dose | 0 Participants |
| Prophylaxis Cohort: TAK-755 (Period 3) | Number of Participants With Acute TTP Events on Their Final Dose | 0 Participants |
| Prophylaxis Cohort: SoC (Periods 1 and 2) | Number of Participants With Acute TTP Events on Their Final Dose | 1 Participants |
Secondary
Number of Participants With Anti-Chinese Hamster Ovary (Anti-CHO) Protein Antibodies During Prophylactic Treatment
Total immunoglobulin antibodies (Immunoglobulin G \[IgG\], A \[IgA\], and M \[IgM\]) against CHO protein were analyzed using ELISA assay. As per planned analysis, data for this outcome measure were collected and reported per sequence (Prophylaxis Cohort I: TAK-755 Then SoC and Prophylaxis Cohort II: SoC Then TAK-755) for the prophylaxis cohorts only.
Time frame: Up to 79.6 months
Population: The Safety Analysis Set included all participants treated with at least 1 dose of TAK-755 or SoC treatment after randomization. A participant initially randomized to Prophylaxis Cohort I received actual treatment as per Prophylaxis Cohort II due to the unavailability of TAK-755 and is presented per actual treatment arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Number of Participants With Anti-Chinese Hamster Ovary (Anti-CHO) Protein Antibodies During Prophylactic Treatment | 0 Participants |
| Prophylaxis Cohort: TAK-755 (Period 3) | Number of Participants With Anti-Chinese Hamster Ovary (Anti-CHO) Protein Antibodies During Prophylactic Treatment | 2 Participants |
Secondary
Number of Participants With Dose Modification Not Prompted by an Acute TTP Event During Prophylactic Treatment
Number of participants with dose modification not prompted by an acute TTP event were reported by treatment for the prophylactic cohort. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.
Time frame: Up to 79.6 months
Population: Modified FAS included all FAS participants with the exclusion of those enrolled prior to November 2017 who were treated with SoC instead of the randomized treatment of TAK-755 in period 1 because TAK-755 was not available. For participants enrolled prior to November 2017, only the first 6 months of SoC treatment in period 1 was included in the analysis. Overall number of participants analyzed indicates the number of participants with data available for analyses.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Number of Participants With Dose Modification Not Prompted by an Acute TTP Event During Prophylactic Treatment | 0 Participants |
| Prophylaxis Cohort: TAK-755 (Period 3) | Number of Participants With Dose Modification Not Prompted by an Acute TTP Event During Prophylactic Treatment | 1 Participants |
| Prophylaxis Cohort: SoC (Periods 1 and 2) | Number of Participants With Dose Modification Not Prompted by an Acute TTP Event During Prophylactic Treatment | 3 Participants |
Secondary
Number of Participants With Inhibitory Antibodies to ADAMTS13
Number of participants with inhibitory antibodies to ADAMTS13 were reported. As per planned analysis, data for this outcome measure were collected and reported in a combined manner irrespective of the Prophylaxis Periods and partitioned as per the treatment received during the course of the study, presented for the prophylaxis cohorts only.
Time frame: Up to 79.6 months
Population: The Safety Analysis Set included all participants treated with at least 1 dose of TAK-755 or SoC treatment after randomization. Overall number of participants analyzed is the number of participants with at least one assessment of the targeted parameter in the specified treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Number of Participants With Inhibitory Antibodies to ADAMTS13 | 1 Participants |
| Prophylaxis Cohort: TAK-755 (Period 3) | Number of Participants With Inhibitory Antibodies to ADAMTS13 | 0 Participants |
Secondary
Number of Participants With Microangiopathic Hemolytic Anemia During Prophylactic Treatment
Microangiopathic hemolytic anemia was defined as an elevation of LDH \>1.5\* of baseline or \>1.5\*ULN (with a possible evidence of schistocytes on blood smear) and was reported by treatment arm for the prophylactic cohort. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.
Time frame: Up to 79.6 months
Population: Modified FAS included all FAS participants with the exclusion of those enrolled prior to November 2017 who were treated with SoC instead of the randomized treatment of TAK-755 in period 1 because TAK-755 was not available. For participants enrolled prior to November 2017, only the first 6 months of SoC treatment in period 1 was included in the analysis. Overall number of participants analyzed indicates the number of participants with data available for analyses.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Number of Participants With Microangiopathic Hemolytic Anemia During Prophylactic Treatment | 8 Participants |
| Prophylaxis Cohort: TAK-755 (Period 3) | Number of Participants With Microangiopathic Hemolytic Anemia During Prophylactic Treatment | 13 Participants |
| Prophylaxis Cohort: SoC (Periods 1 and 2) | Number of Participants With Microangiopathic Hemolytic Anemia During Prophylactic Treatment | 12 Participants |
Secondary
Number of Participants With Neurological Symptoms During Prophylactic Treatment
Neurological symptoms (TTP related) (e.g., confusion, dysphonia, dysarthria, focal or general motor symptoms including seizures), were reported by treatment arm for the prophylactic cohort. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.
Time frame: Up to 79.6 months
Population: Modified FAS included all FAS participants with the exclusion of those enrolled prior to November 2017 who were treated with SoC instead of the randomized treatment of TAK-755 in period 1 because TAK-755 was not available. For participants enrolled prior to November 2017, only the first 6 months of SoC treatment in period 1 was included in the analysis. Overall number of participants analyzed indicates the number of participants with data available for analyses.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Number of Participants With Neurological Symptoms During Prophylactic Treatment | 4 Participants |
| Prophylaxis Cohort: TAK-755 (Period 3) | Number of Participants With Neurological Symptoms During Prophylactic Treatment | 9 Participants |
| Prophylaxis Cohort: SoC (Periods 1 and 2) | Number of Participants With Neurological Symptoms During Prophylactic Treatment | 7 Participants |
Secondary
Number of Participants With Neutralizing Antibodies to ADAMTS13 During Prophylactic Treatment
Neutralizing antibodies were measured by a Bethesda method with Nijmegen modification using the ADAMTS13 FRETS-VWF73 activity assay. As per planned analysis, data for this outcome measure were collected and reported per sequence (Prophylaxis Cohort I: TAK-755 Then SoC and Prophylaxis Cohort II: SoC Then TAK-755) for the prophylaxis cohorts only.
Time frame: Up to 79.6 months
Population: The Safety Analysis Set included all participants treated with at least 1 dose of TAK-755 or SoC treatment after randomization. A participant initially randomized to Prophylaxis Cohort I received actual treatment as per Prophylaxis Cohort II due to the unavailability of TAK-755 and is presented per actual treatment arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Number of Participants With Neutralizing Antibodies to ADAMTS13 During Prophylactic Treatment | 0 Participants |
| Prophylaxis Cohort: TAK-755 (Period 3) | Number of Participants With Neutralizing Antibodies to ADAMTS13 During Prophylactic Treatment | 1 Participants |
Secondary
Number of Participants With Renal Dysfunction During Prophylactic Treatment
Renal dysfunction was defined as an increase in serum creatinine \>1.5\*baseline. Number of participants with renal dysfunction were reported by treatment arm for the prophylactic cohort. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.
Time frame: Up to 79.6 months
Population: Modified FAS included all FAS participants with the exclusion of those enrolled prior to November 2017 who were treated with SoC instead of the randomized treatment of TAK-755 in period 1 because TAK-755 was not available. For participants enrolled prior to November 2017, only the first 6 months of SoC treatment in period 1 was included in the analysis. Overall number of participants analyzed indicates the number of participants with data available for analyses.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Number of Participants With Renal Dysfunction During Prophylactic Treatment | 5 Participants |
| Prophylaxis Cohort: TAK-755 (Period 3) | Number of Participants With Renal Dysfunction During Prophylactic Treatment | 4 Participants |
| Prophylaxis Cohort: SoC (Periods 1 and 2) | Number of Participants With Renal Dysfunction During Prophylactic Treatment | 2 Participants |
Secondary
Number of Participants With Thrombocytopenia During Prophylactic Treatment
Thrombocytopenia was defined as a decrease in platelet count ≥25 % of baseline or a platelet count \<150,000/μL, reported by treatment arm for the prophylactic cohort. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.
Time frame: Up to 79.6 months
Population: Modified FAS included all FAS participants with the exclusion of those enrolled prior to November 2017 who were treated with SoC instead of the randomized treatment of TAK-755 in period 1 because TAK-755 was not available. For participants enrolled prior to November 2017, only the first 6 months of SoC treatment in period 1 was included in the analysis. Overall number of participants analyzed indicates the number of participants with data available for analyses.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Number of Participants With Thrombocytopenia During Prophylactic Treatment | 13 Participants |
| Prophylaxis Cohort: TAK-755 (Period 3) | Number of Participants With Thrombocytopenia During Prophylactic Treatment | 11 Participants |
| Prophylaxis Cohort: SoC (Periods 1 and 2) | Number of Participants With Thrombocytopenia During Prophylactic Treatment | 22 Participants |
Secondary
Number of Participants With Total Binding Antibodies to ADAMTS13 During Prophylactic Treatment
Total binding antibodies to ADAMTS13 were measured by an ELISA-based assay, detecting total immunoglobulins (IgG, IgA, and IgM). As per planned analysis, data for this outcome measure were collected and reported per sequence (Prophylaxis Cohort I: TAK-755 Then SoC and Prophylaxis Cohort II: SoC Then TAK-755) for the prophylaxis cohorts only.
Time frame: Up to 79.6 months
Population: The Safety Analysis Set included all participants treated with at least 1 dose of TAK-755 or SoC treatment after randomization. A participant initially randomized to Prophylaxis Cohort I received actual treatment as per Prophylaxis Cohort II due to the unavailability of TAK-755 and is presented per actual treatment arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Number of Participants With Total Binding Antibodies to ADAMTS13 During Prophylactic Treatment | 0 Participants |
| Prophylaxis Cohort: TAK-755 (Period 3) | Number of Participants With Total Binding Antibodies to ADAMTS13 During Prophylactic Treatment | 2 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Treatment Emergent Adverse Events (Serious TEAEs)
AE: Any untoward medical occurrence in participants administered IP that does not necessarily have a causal relationship with treatment. TEAE: AE that has start date-time on/after start date-time of first dose of treatment participant is taking on that assessment/period or if it has start date-time before start date-time of first dose but increases in severity on/after start date-time of the first dose of treatment. SAE: An untoward medical occurrence that at any dose meets 1 or more of following criteria: death; initial/prolonged in-patient hospitalization; life threatening experience; persistent/significant disability/incapacity; congenital anomaly, medically important event (may not be immediately life threatening or result in death or require hospitalization but may require medical or surgical intervention to prevent 1 of the other outcomes). Vital signs, clinical chemistry, hematology as assessed by the investigator were reported as AE.
Time frame: Up to 79.6 months
Population: The Safety Analysis Set included all participants treated with at least 1 dose of TAK-755 or SoC treatment after randomization. As per planned analysis, data for this outcome measure were collected and reported in a combined manner irrespective of the Prophylaxis Periods and partitioned as per the treatment received during the course of the study, presented for the on demand and prophylaxis cohorts.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Treatment Emergent Adverse Events (Serious TEAEs) | TEAES | 42 Participants |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Treatment Emergent Adverse Events (Serious TEAEs) | Serious TEAEs | 6 Participants |
| Prophylaxis Cohort: TAK-755 (Period 3) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Treatment Emergent Adverse Events (Serious TEAEs) | Serious TEAEs | 8 Participants |
| Prophylaxis Cohort: TAK-755 (Period 3) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Treatment Emergent Adverse Events (Serious TEAEs) | TEAES | 44 Participants |
| Prophylaxis Cohort: SoC (Periods 1 and 2) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Treatment Emergent Adverse Events (Serious TEAEs) | TEAES | 0 Participants |
| Prophylaxis Cohort: SoC (Periods 1 and 2) | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Treatment Emergent Adverse Events (Serious TEAEs) | Serious TEAEs | 0 Participants |
| On Demand Cohort II: SoC | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Treatment Emergent Adverse Events (Serious TEAEs) | TEAES | 3 Participants |
| On Demand Cohort II: SoC | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Treatment Emergent Adverse Events (Serious TEAEs) | Serious TEAEs | 1 Participants |
Secondary
Number of Supplemental Doses Prompted by Subacute TTP Event During Prophylactic Treatment
Number of supplemental doses prompted by subacute TTP events were reported by treatment for the prophylactic cohort. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts, in a combined manner for Periods 1 and 2 for TAK-755 and SoC treatments respectively, and separately for Period 3 in which all participants received TAK-755.
Time frame: Up to 79.6 months
Population: Modified FAS included all FAS participants with the exclusion of those enrolled prior to November 2017 who were treated with SoC instead of the randomized treatment of TAK-755 in period 1 because TAK-755 was not available. For participants enrolled prior to November 2017, only the first 6 months of SoC treatment in period 1 was included in the analysis. Overall number of participants analyzed indicates the number of participants with data available for analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Number of Supplemental Doses Prompted by Subacute TTP Event During Prophylactic Treatment | 0 supplemental doses |
| Prophylaxis Cohort: TAK-755 (Period 3) | Number of Supplemental Doses Prompted by Subacute TTP Event During Prophylactic Treatment | 5 supplemental doses |
| Prophylaxis Cohort: SoC (Periods 1 and 2) | Number of Supplemental Doses Prompted by Subacute TTP Event During Prophylactic Treatment | 9 supplemental doses |
Secondary
Percentage of Acute Thrombotic Thrombocytopenic Purpura (TTP) Events Responding to TAK-755
Percentage of acute TTP events responding to TAK-755, was defined as not requiring the use of another human disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13 (ADAMTS13)-containing agent. As per planned analysis, data for this outcome measure were collected and reported only for the TAK-755 treatment arm of both the prophylaxis (irrespective of the prophylaxis periods) and on demand cohorts.
Time frame: Up to 79.6 months
Population: Modified FAS included all FAS participants with the exclusion of those enrolled prior to November 2017 who were treated with SoC instead of the randomized treatment of TAK-755 in period 1 because TAK-755 was not available. For participants enrolled prior to November 2017, only the first 6 months of SoC treatment in period 1 was included in the analysis. Overall number of participants=participants with acute TTP events that were confirmed by central lab data treated with TAK-755.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prophylaxis Cohort: TAK-755 (Period 3) | Percentage of Acute Thrombotic Thrombocytopenic Purpura (TTP) Events Responding to TAK-755 | 100 percentage of events |
Secondary
Resource Utilization: Annualized Length of Hospital Stay for Acute TTP Events for Prophylaxis Cohorts
The annualized number of days participants stayed in hospital for acute TTP events were assessed. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts in a combined manner for Periods 1 and 2 for SoC treatment and for Periods 1, 2, and 3 for TAK-755 treatment respectively.
Time frame: Up to 79.6 months
Population: Modified FAS included all FAS participants with the exclusion of those enrolled prior to November 2017 who were treated with SoC instead of the randomized treatment of TAK-755 in period 1 because TAK-755 was not available. For participants enrolled prior to November 2017, only the first 6 months of SoC treatment in period 1 was included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Resource Utilization: Annualized Length of Hospital Stay for Acute TTP Events for Prophylaxis Cohorts | 0.00 days/year |
| Prophylaxis Cohort: TAK-755 (Period 3) | Resource Utilization: Annualized Length of Hospital Stay for Acute TTP Events for Prophylaxis Cohorts | 0.00 days/year |
Secondary
Resource Utilization: Annualized Number of Acute Care Visits for Prophylaxis Cohorts
Annualized number of acute care visits was calculated as the number of acute care visits × 365.25/(End date - treatment start date + 1). As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts in a combined manner for Periods 1 and 2 for SoC treatment and for Periods 1, 2, and 3 for TAK-755 treatment respectively.
Time frame: Up to 79.6 months
Population: Modified FAS included all FAS participants with the exclusion of those enrolled prior to November 2017 who were treated with SoC instead of the randomized treatment of TAK-755 in period 1 because TAK-755 was not available. For participants enrolled prior to November 2017, only the first 6 months of SoC treatment in period 1 was included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Resource Utilization: Annualized Number of Acute Care Visits for Prophylaxis Cohorts | 0.59 acute care visits per year | Standard Deviation 1.378 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Resource Utilization: Annualized Number of Acute Care Visits for Prophylaxis Cohorts | 0.14 acute care visits per year | Standard Deviation 0.493 |
Secondary
Resource Utilization: Annualized Number of Days Missed From School or Work for Prophylaxis Cohorts
Annualized number of days missed from school or work were assessed. As per planned analysis, data for this outcome measure were collected and reported only for the prophylaxis cohorts in a combined manner for Periods 1 and 2 for SoC treatment and for Periods 1, 2, and 3 for TAK-755 treatment respectively.
Time frame: Up to 79.6 months
Population: Modified FAS included all FAS participants with the exclusion of those enrolled prior to November 2017 who were treated with SoC instead of the randomized treatment of TAK-755 in period 1 because TAK-755 was not available. For participants enrolled prior to November 2017, only the first 6 months of SoC treatment in period 1 was included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Resource Utilization: Annualized Number of Days Missed From School or Work for Prophylaxis Cohorts | 0.00 days/year |
| Prophylaxis Cohort: TAK-755 (Period 3) | Resource Utilization: Annualized Number of Days Missed From School or Work for Prophylaxis Cohorts | 0.00 days/year |
Secondary
Terminal Half-Life (t1/2) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment
PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
Time frame: PK-I (Month 1:Day 1 up to 12), PK-II (Month 12:Day 1 up to 12), and PK-III (Month 19:Day 1 up to 12): Pre-infusion and at multiple timepoints post-infusion up to 288 hours
Population: The PK Analysis Set included all FAS participants who had adequate post-dose PK measurements for at least one of the PK analytes without major protocol deviations or events that may affect the integrity of the PK data. Overall number of participants analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses in the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Terminal Half-Life (t1/2) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-II: ADAMTS13 Activity | 52.51 hours | Standard Deviation 15.579 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Terminal Half-Life (t1/2) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I: ADAMTS13 Activity | 47.14 hours | Standard Deviation 11.573 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Terminal Half-Life (t1/2) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I: ADAMTS13 Antigen | 53.65 hours | Standard Deviation 13.557 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Terminal Half-Life (t1/2) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-II: ADAMTS13 Antigen | 54.04 hours | Standard Deviation 16.899 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Terminal Half-Life (t1/2) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-III: ADAMTS13 Antigen | 39.85 hours | Standard Deviation 3.243 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Terminal Half-Life (t1/2) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-II: ADAMTS13 Activity | 45.77 hours | Standard Deviation 9.996 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Terminal Half-Life (t1/2) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-II: ADAMTS13 Antigen | 49.72 hours | Standard Deviation 15.942 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Terminal Half-Life (t1/2) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-III: ADAMTS13 Activity | 35.38 hours | Standard Deviation 5.286 |
| Prophylaxis Cohort: SoC (Periods 1 and 2) | Terminal Half-Life (t1/2) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I: ADAMTS13 Antigen | 58.70 hours | Standard Deviation 23.575 |
| Prophylaxis Cohort: SoC (Periods 1 and 2) | Terminal Half-Life (t1/2) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I: ADAMTS13 Activity | 62.88 hours | Standard Deviation 28.927 |
Secondary
Time to Resolution of Acute TTP Events
Time to resolution of acute TTP events following initiation of treatment with TAK-755 or SoC agent was assessed. Acute TPP events were considered resolved when: (a) Platelet count was \>150,000 per microliter (μL) or drop of platelet count was within 25 percent (%) of baseline, whichever occurred first, and (b) Elevation of lactate dehydrogenase (LDH) \<1.5 x baseline or \<1.5 x upper limit of normal (ULN). As per planned analysis, data for this outcome measure were collected and reported in a combined manner irrespective of the prophylaxis treatment Periods, partitioned per treatment received (TAK-755 and SoC) for the on demand and prophylactic cohorts.
Time frame: Up to 79.6 months
Population: Modified FAS= all FAS participants with the exclusion of those enrolled prior to November(Nov.) 2017 who were treated with SoC instead of the randomized treatment of TAK-755 in period 1 because TAK-755 was not available. For participants enrolled prior to Nov. 2017, only the first 6 months of SoC treatment in period 1 was included in the analysis. Overall number of participants analyzed= the number of only those participants with acute TTP events that were confirmed by central lab data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Prophylaxis Cohort: TAK-755 (Period 3) | Time to Resolution of Acute TTP Events | 14.8 days |
| Prophylaxis Cohort: SoC (Periods 1 and 2) | Time to Resolution of Acute TTP Events | 3.0 days |
| On Demand Cohort II: SoC | Time to Resolution of Acute TTP Events | 1.5 days |
Secondary
Total Quantity of ADAMTS13 Administered During the Treatment of Acute TTP Events in Participants in TAK-755 Treatment Arm
Total quantity of ADAMTS13 administered during the treatment of acute TTP events (all acute TTP events irrespective of central lab confirmation were included) was assessed. Acute TTP events typically require 3 to 4 days of intensified treatment. As per planned analysis, data for this outcome measure were collected and reported only for the TAK-755 treatment arm of both the prophylaxis (irrespective of the prophylaxis periods) and on demand cohorts.
Time frame: Up to 79.6 months
Population: The Safety Analysis Set included all participants treated with at least 1 dose of TAK-755 or SoC treatment after randomization. Overall number of participants analyzed is the number of participants with at least one assessment of the targeted parameter in the specified treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prophylaxis Cohort: TAK-755 (Period 3) | Total Quantity of ADAMTS13 Administered During the Treatment of Acute TTP Events in Participants in TAK-755 Treatment Arm | 5720.25 IU | Standard Deviation 189.858 |
Secondary
Volume at Steady State (Vss) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment
PK-I, PK-II, and PK-III denote the crossover PK evaluation of a maximum of 14 days at the start of Prophylaxis Treatment Period 1 and end of Prophylaxis Treatment Periods 2 and 3 respectively. As per planned analysis, data for this outcome measure were collected and reported as per the treatment (intervention) received (rADAMTS13 manufactured in Orth, Austria \[TAK-755 ORT\], rADAMTS13 manufactured in Singapore \[TAK-755 SIN\], or SoC) during the course of the study, only for the prophylaxis cohorts. No participants received SoC in PK-II and PK-III thus there is no data for the same.
Time frame: PK-I (Month 1:Day 1 up to 12), PK-II (Month 12:Day 1 up to 12), and PK-III (Month 19:Day 1 up to 12): Pre-infusion and at multiple timepoints post-infusion up to 288 hours
Population: The PK Analysis Set included all FAS participants who had adequate post-dose PK measurements for at least one of the PK analytes without major protocol deviations or events that may affect the integrity of the PK data. Overall number of participants analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses in the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Volume at Steady State (Vss) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-II: ADAMTS13 Activity | 3.401 liters | Standard Deviation 0.715 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Volume at Steady State (Vss) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I: ADAMTS13 Activity | 3.855 liters | Standard Deviation 0.911 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Volume at Steady State (Vss) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I: ADAMTS13 Antigen | 3.120 liters | Standard Deviation 0.657 |
| Prophylaxis Cohort: TAK-755 (Periods 1 and 2) | Volume at Steady State (Vss) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-II: ADAMTS13 Antigen | 2.791 liters | Standard Deviation 0.48 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Volume at Steady State (Vss) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-III: ADAMTS13 Antigen | 2.164 liters | Standard Deviation 0.625 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Volume at Steady State (Vss) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-II: ADAMTS13 Activity | 3.328 liters | Standard Deviation 0.631 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Volume at Steady State (Vss) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-II: ADAMTS13 Antigen | 3.009 liters | Standard Deviation 0.614 |
| Prophylaxis Cohort: TAK-755 (Period 3) | Volume at Steady State (Vss) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-III: ADAMTS13 Activity | 2.265 liters | Standard Deviation 0.669 |
| Prophylaxis Cohort: SoC (Periods 1 and 2) | Volume at Steady State (Vss) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I: ADAMTS13 Antigen | NA liters | — |
| Prophylaxis Cohort: SoC (Periods 1 and 2) | Volume at Steady State (Vss) of ADAMTS13 Activity and ADAMTS13 Antigen for SoC Agent and TAK-755 in Plasma During Prophylactic Treatment | PK-I: ADAMTS13 Activity | NA liters | — |