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

NCT03393975 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: 2811022017-000858-18TAK-755-281102
• Study Type: interventional
• Target: 52
• Locations: 9 countries
• Sites: 33

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.

Conditions

Thrombotic Thrombocytopenic Purpura (TTP)

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 74.5 months

Secondary Outcomes (43)

• Percentage of Acute Thrombotic Thrombocytopenic Purpura (TTP) Events Responding to TAK-755

  Up to 79.6 months

• Time to Resolution of Acute TTP Events

  Up to 79.6 months

• Number of Participants With Thrombocytopenia During Prophylactic Treatment

  Up to 79.6 months

• Number of Participants With Microangiopathic Hemolytic Anemia During Prophylactic Treatment

  Up to 79.6 months

• Number of Participants With Neurological Symptoms During Prophylactic Treatment

  Up to 79.6 months

Study Arms (4)

Prophylaxis Cohort I: TAK-755 Then SoC

EXPERIMENTAL

Participants received a single intravenous (IV) infusion of 40 international units per kilogram (IU/kg) rADAMTS13 manufactured in Orth, Austria (TAK-755 ORT), every 2 weeks (Q2W) for 6 months in Period 1 followed by standard of care (SoC) for 6 months in Period 2. Thereafter participants received rADAMTS13 manufactured in Singapore (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.

Biological: TAK-755; Biological: Standard of care

Prophylaxis Cohort II: SoC Then TAK-755

EXPERIMENTAL

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.

Biological: TAK-755; Biological: Standard of care

On Demand Cohort I: TAK-755

EXPERIMENTAL

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 infusion 40 IU/kg \[+/- 4 IU/kg\] TAK-755 ORT or TAK-755 SIN on Day 1 followed by a subsequent dose IV infusions 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.

Biological: TAK-755

On Demand Cohort II: SoC

EXPERIMENTAL

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.

Biological: Standard of care

Interventions

TAK-755 BIOLOGICAL

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.

Also known as: rADAMTS13, SHP-655, recombinant ADAMTS13, BAX 930

On Demand Cohort I: TAK-755; Prophylaxis Cohort I: TAK-755 Then SoC; Prophylaxis Cohort II: SoC Then TAK-755

Standard of care BIOLOGICAL

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

On Demand Cohort II: SoC; Prophylaxis Cohort I: TAK-755 Then SoC; Prophylaxis Cohort II: SoC Then TAK-755

Eligibility Criteria

• Age: 0 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Baxalta now part of Shire: lead
• Takeda Development Center Americas, Inc.: collaborator

Study Sites (33)

Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Alliance for Childhood Diseases, Cure 4 the Kids Foundation

Las Vegas, Nevada, 89135, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Ohio State Univ College Of Medicine

Columbus, Ohio, 43210, United States

Location

University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

Location

The Methodist Hospital

Houston, Texas, 77030, United States

Location

AKH - Medizinische Universität Wien

Vienna, 1090, Austria

Location

Hopital Claude Huriez - CHU Lille

Lille, Nord, 59037, France

Location

Hôpital Necker - Enfants Malades

Paris, Paris, 75015, France

Location

Hôpital Saint-Antoine

Paris, Paris, 75571, France

Location

CHU Saint Etienne - Hôpital Nord

Saint-Priest-en-Jarez Cedex, Pays de la Loire Region, 42270, France

Location

Hôpital Robert Debré - Paris

Paris, 75019, France

Location

Universitaetsklinikum Jena

Jena, Thuringia, 07747, Germany

Location

Universitaetsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

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

Bergamo, 24127, Italy

Location

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

Catania, 90124, Italy

Location

Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, 168, Italy

Location

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

Rome, 00161, Italy

Location

Kyushu University Hospital

Fukuoka, Fukuoka, 812-8582, Japan

Location

Hyogo College of Medicine Hospital

Nishinomiya-shi, Hyōgo, 663-8501, Japan

Location

Medical Hospital, Tokyo Medical and Dental University

Bunkyō City, Tokyo-To, 113-8519, Japan

Location

Samodzielny Publiczny Dzieciecy Szpital Kliniczny

Warsaw, 02-091, Poland

Location

Instytut Hematologii i Transfuzjologii

Warsaw, 02-776, Poland

Location

Complejo Hospitalario Universitario A Coruña

A Coruña, La Coruña, 15006, Spain

Location

Hospital de Cruces

Barakaldo, Vizcaya, 48903, Spain

Location

Hospital General Universitario de Alicante

Alicante, 3010, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

Location

University College London Hospitals

London, Greater London, NW1 2PG, United Kingdom

Location

Royal Manchester Children's Hospital

Manchester, M139WL, United Kingdom

Location

Related Publications (1)

• Scully M, Antun A, Cataland SR, Coppo P, Dossier C, Biebuyck N, Hassenpflug WA, Kentouche K, Knobl P, Kremer Hovinga JA, Lopez-Fernandez MF, Matsumoto M, Ortel TL, Windyga J, Bhattacharya I, Cronin M, Li H, Mellgard B, Patel M, Patwari P, Xiao S, Zhang P, Wang LT; cTTP Phase 3 Study Investigators. Recombinant ADAMTS13 in Congenital Thrombotic Thrombocytopenic Purpura. N Engl J Med. 2024 May 2;390(17):1584-1596. doi: 10.1056/NEJMoa2314793.

  PMID: 38692292 DERIVED

Related Links

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

MeSH Terms

Conditions

Purpura, Thrombotic Thrombocytopenic

Interventions

ADAMTS13 protein, human; Standard of Care

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Thrombophilia; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Shire

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: October 5, 2017
• First Posted: January 9, 2018
• Study Start: October 13, 2017
• Primary Completion: December 28, 2023
• Study Completion: May 30, 2024
• Last Updated: February 9, 2026
• Results First Posted: March 19, 2025

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

ES (6); GB (2); AU (1); FR (5); IT (5); DE (2); JP (3); US (7); PL (2)