Phase 1 clinical study to assess safety of single infusions of rADAMTS13 (BAX930) in humans and to evaluate distribution and elimination of rADAMTS13 (BAX930) from the human body after administration at 3 different dose levels in patients diagnosed with severe hereditary TTP

• Register: EUCTR
• Last refreshed on: 11 April 2016
• Main ID: EUCTR2012-003221-19-AT
• Date of registration: 12/11/2012
• Prospective Registration: Yes
• Primary sponsor: Baxalta Innovations GmbH
• Public title: Phase 1 clinical study to assess safety of single infusions of rADAMTS13 (BAX930) in humans and to evaluate distribution and elimination of rADAMTS13 (BAX930) from the human body after administration at 3 different dose levels in patients diagnosed with severe hereditary TTP
• Scientific title: BAX 930 (rADAMTS13) A PHASE 1 PROSPECTIVE, UNCONTROLLED, OPEN-LABEL, MULTICENTER, DOSE-ESCALATION STUDY EVALUATING THE SAFETY AND PHARMACOKINETICS IN HEREDITARY TTP (THROMBOTIC THROMBOCYTOPENIC PURPURA) - Phase 1 dose escalation, single dose, to assess safety and PK of BAX930 in hTTP
• Date of first enrolment: 17/12/2012
• Target sample size: 14
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-003221-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: Dose escalation If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Austria, Germany, Japan, Poland, United Kingdom, United States

Contacts

• Name: Manfred Rieger
• Affiliation: Baxalta Innovations GmbH

• Name: Manfred Rieger
• Affiliation: Baxalta Innovations GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
-Subject is between 12 and 65 years of age, inclusive. The first two subjects in any Cohort will be = 18 years of age.
-The subject has a documented diagnosis of severe hereditary ADAMTS13 deficiency
-Cryoprecipitate, FFP, or other ADAMTS13 containing products interfering with ADAMTS13 PK have to be paused at least 10 days prior infusion of the IP.
-The subject is not displaying any severe TTP symptoms at screening.
-Subjects =18 years of age have a Karnofsky score = 60% and subjects < 18 years of age have a Lansky score = 70%.
-If female of childbearing potential, subject presents with a negative serum pregnancy test and agrees to employ adequate birth control measures for the duration of the study.

For the entire list of inclusion criteria refer to protocol section 9.1
Are the trial subjects under 18? yes
Number of subjects for this age range: 3
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1

Exclusion criteria:
-The subject has been diagnosed with any other TTP-like disorder (for eg, microangiopathic hemolytic anemia), including acquired TTP.
-The subject has a medical history or presence of a functional neutralizing ADAMTS13 inhibitor at screening.
-The subject has a medical history of immunological disorders, excluding seasonal allergic rhinitis/conjunctivitis/mild asthma, food allergies or animal allergies.
-The subject has a medical history of hematological disorders, in particular systemic lupus erythematosus, amyloidosis, antiphospholipid antibody syndrome, vasculitis, other hemolytic anemia, disseminated intravascular coagulation, and systemic scleroderma.
-The subject has a history of significant neurological events, such as major stroke, indicating that a relapse might have severe consequences, as judged by the investigator.
-The subject has been diagnosed with a cardiovascular disease [New York Heart Association (NYHA) classes 3-4].
-The subject has been diagnosed with severe liver disease, as evidenced by, but not limited to, any of the following: serum ALT 3 times the upper limit of normal, INR > 1.5, hypoalbuminemia, portal vein hypertension (e.g. presence of otherwise unexplained splenomegaly, history of esophageal varices).
-The subject has been diagnosed with severe glomerular disease, with gross proteinuria and a serum creatinine level = 2.5 mg/dL.
-If female, subject is pregnant or lactating at the time of study enrollment.

For the entire list of inclusion criteria refer to protocol section 9.2


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Subjects diagnosed with hereditary thrombotic thrombocytopenic purpura (TTP)
MedDRA version: 18.0 Level: LLT Classification code 10043562 Term: Thrombocytopenic purpura, thrombotic System Organ Class: 100000004851

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Intervention(s)

Product Name: Recombinant A Disintegrin and Metalloproteinase with Thrombospondin Type-1 Motifs 13
Product Code: BAX930
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: Recombinant A Disintegrin and Metalloproteinase with Thrombospondin Type-1 Motifs 13
Current Sponsor code: BAX930
Concentration unit: IU/kg international unit(s)/kilogram
Concentration type: up to
Concentration number: 40-

Primary Outcome(s)

Primary end point(s): Occurrence of adverse events (serious and non-serious), including the incidence of binding and inhibitory antibody formation, occurring up to 28 ± 3 days after the last investigational product infusion.

Main Objective: To evaluate the safety of BAX930 following single infusions at doses of 5, 20, and 40 U/kg BW, including the occurrence of adverse events (serious and non-serious) and formation of binding and inhibitory antibodies to BAX 930.

Secondary Objective: -To evaluate the pharmacokinetics of BAX 930 following single infusions of rADAMTS13 at doses of 5, 20, and 40 U/kg BW
-To evaluate the effect of BAX930 on plasma VWF levels and multimeric patterns

Timepoint(s) of evaluation of this end point: At specified timepoints following IP infusion and at study completion (28 ± 3 days after the last investigational product infusion)in each dose cohort.

Secondary Outcome(s)

Secondary end point(s): -Standard pharmacokinetic parameters for ADAMTS13 activity and ADAMTS13:Ag after single infusions of rADAMTS13 in Dose Cohorts 1, 2 and 3;
-Measurement of plasma VWF:RCo, VWF:Ag and VWF structure analysis prior to and following a single infusion of rADAMTS13.

Timepoint(s) of evaluation of this end point: At specified timepoints following IP infusion and at study completion (28 ± 3 days after the last investigational product infusion) in each dose cohort.

Secondary ID(s)

281101

Source(s) of Monetary Support

Baxalta Innovations GmbH