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

A Phase 3, Prospective, Randomized, Controlled, Open-label, Multicenter, 2 Period Crossover Study With a Single Arm Continuation Evaluating the Safety And Efficacy of BAX 930 (rADAMTS13) in the Prophylactic And On-demand Treatment of Subjects With Severe Congenital Thrombotic Thrombocytopenic Purpura (cTTP, Upshaw-Schulman Syndrome [USS], Hereditary Thrombotic Thrombocytopenic Purpura [hTTP])

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.

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.