A Phase 3, randomized, controlled study in the treatment of severe congenital thrombotic thrombocytopenic purpura, with BAX 930.

Phase 1

• Conditions: severe congenital thrombotic thrombocytopenic purpura(cTTP, Upshaw-Schulman Syndrome [USS], hereditary thromboticthrombocytopenic purpura [hTTP]); MedDRA version: 20.0Level: LLTClassification code 10043562Term: Thrombocytopenic purpura, thromboticSystem Organ Class: 100000004851; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2017-000858-18-DE
• Lead Sponsor: Baxalta Innovations GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-08-31
• Last Update Posted: 10 June 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 57

Inclusion Criteria

1. Subject or legally authorized representative has provided signed informed consent (=18 years of age) and/or assent form (signed by legal representative if subject is <18 years of age).
2. Subject is 0 to 70 years of age, inclusive, at the time of screening. (Subjects <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 DMC). In France, no subjects younger than 18 years of age will be enrolled into the study before the first adult subject has been treated with BAX 930 for a minimum of 6 months.).
3. Subject has a documented diagnosis of severe hereditary ADAMTS13 deficiency, defined as:
· Confirmed by molecular genetic testing, documented in subject history or at screening, and
· ADAMTS13 activity <10% as measured by the FRETS-VWF73 assay, documented in subject history or at screening (subjects currently receiving SoC prophylactic therapy may exceed 10% ADAMTS13 activity at screening).
Note: Subjects currently receiving prophylactic therapy will be screened immediately prior to their usual prophylactic infusion
4.Subject does not display any severe TTP symptoms signs (platelet count <100,000/µL and elevation of LDH >2×ULN) at screening. Subjects presenting with minor, but stable laboratory abnormalities at the time of screening may be enrolled (prophylactic cohort only).
5. Subject 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).
6. Subjects =16 years of age must have a Karnofsky score =70% and subjects <16 years of age must have a Lansky score =80%.
7. Subject 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.
8. If female of childbearing potential, subject 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.
9. 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.
10. Subject is willing and able to comply with the requirements of the protocol.
Are the trial subjects under 18? yes
Number of subjects for this age range: 15
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

Exclusion Criteria

1. Subject has been diagnosed with any other TTP-like disorder (microangiopathic hemolytic anemia), including acquired TTP.
2. Subject has known hypersensitivity to hamster proteins.
3. Subject has experienced an acute TTP episode less than 30 days prior to screening (prophylactic cohort only).
4. Subject has a medical history or presence of a functional ADAMTS13 inhibitor at screening.
5. Subject has a medical history of a genetic or acquired immune deficiency that would interfere with the assessment of product immunogenicity, including subjects who are human immunodeficiency virus (HIV) positive with an absolute cluster of differentiation 4 (CD4) count <200/mm3 or who are
receiving chronic immunosuppressive drugs.
6. Subject has been diagnosed with severe cardiovascular disease (New York Heart Association classes 3 to 4).
7. Subject with end stage renal disease requiring chronic dialysis.
8. Subject has been diagnosed with hepatic dysfunction, as evidenced by, but not limited to, any of the following:
a. Serum alanine aminotransferase (ALT) =2xULN
b. Severe hypoalbuminemia <24 g/L
c. Portal vein hypertension (e.g., presence of otherwise unexplained splenomegaly, history of esophageal varices)
9. In the opinion of the investigator, the subject has another clinically significant concomitant disease that may pose additional risks for the subject.
10. Subject 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 FFP to prevent allergic reactions is permitted.
11. Subject has an acute illness (e.g., influenza, flu-like syndrome, allergic rhinitis/conjunctivitis, bronchial asthma) at the time of screening (prophylaxis cohort only).
12. Subject is receiving or anticipates receiving another investigational drug and/or interventional drug within 30 days before enrollment.
13. Subject has a history of drug and/or alcohol abuse within the last 2 years.
14. Subject has a progressive fatal disease and/or life expectancy of less than 3 months.
15. Subject is identified by the investigator as being unable or unwilling to cooperate with study procedures.
16. Subject 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.
17. Subject is a family member or employee of the sponsor or investigator.
18. If female, subject is pregnant or lactating at the time of enrolment.
19. Any contraindication to standard of care medicinal product(s) as per local prescribing information

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified