Clinical Trials Register

Summary
EudraCT Number:	2012-003221-19
Sponsor's Protocol Code Number:	281101
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-12-13
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2012-003221-19

A.3

Full title of the trial

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)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

A.3.2

Name or abbreviated title of the trial where available

Phase 1 dose escalation, single dose, to assess safety and PK of BAX930 in hTTP

A.4.1

Sponsor's protocol code number

281101

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/48/2012

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Baxalta Innovations GmbH
B.1.3.4	Country	Austria
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Baxalta Innovations GmbH
B.4.2	Country	Austria
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Baxalta Innovations GmbH
B.5.2	Functional name of contact point	Manfred Rieger
B.5.3	Address:
B.5.3.1	Street Address	Donau City Strasse 7
B.5.3.2	Town/ city	Vienna
B.5.3.3	Post code	1221
B.5.3.4	Country	Austria
B.5.4	Telephone number	+431201002473438
B.5.5	Fax number	+43120100717
B.5.6	E-mail	Manfred.Rieger@baxalta.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/08/588
D.3 Description of the IMP
D.3.1	Product name	Recombinant A Disintegrin and Metalloproteinase with Thrombospondin Type-1 Motifs 13
D.3.2	Product code	BAX930
D.3.4	Pharmaceutical form	Powder and solvent for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Recombinant A Disintegrin and Metalloproteinase with Thrombospondin Type-1 Motifs 13
D.3.9.2	Current sponsor code	BAX930
D.3.10	Strength
D.3.10.1	Concentration unit	IU/kg international unit(s)/kilogram
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	40
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Subjects diagnosed with hereditary thrombotic thrombocytopenic purpura (TTP)

E.1.1.1

Medical condition in easily understood language

Subjects diagnosed with hereditary thrombotic thrombocytopenic purpura (TTP)

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.0
E.1.2	Level	LLT
E.1.2	Classification code	10043562
E.1.2	Term	Thrombocytopenic purpura, thrombotic
E.1.2	System Organ Class	100000004851

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

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.

E.2.2

Secondary objectives of the trial

-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

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Subject is between 18 and 65 years of age, inclusive.
-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%.
-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

E.4

Principal 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

E.5 End points

E.5.1

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.

E.5.1.1

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.

E.5.2

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.

E.5.2.1

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.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

Yes

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Dose escalation

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Japan

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Adolescents

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2013-01-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-02-05

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-02-22

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