Hereditary Thrombotic Thrombocytopenic Purpura (TTP)Phase 1NCT02216084
Phase 1 Dose Escalation, Single Dose Study to Assess Safety and Pharmacokinetics of BAX930 in Hereditary Thrombotic Thrombocytopenic Purpura (TTP)
A Phase 1 study testing Recombinant ADAMTS13 in people with Hereditary Thrombotic Thrombocytopenic Purpura (TTP), run by Baxalta now part of Shire at 11 sites in 7 countries.
Trial summary
The purpose of this Phase 1, prospective, uncontrolled, open-label, multicenter, dose-escalation study is to evaluate the safety, including immunogenicity, and pharmacokinetics of BAX930 (rADAMTS13) in a total of 14 evaluable subjects diagnosed with severe hereditary thrombotic thrombocytopenic purpura (TTP) (plasma… Read more about this study
- Who is it for?
- Ages 12 to 65 years
- Conditions the study is for
- Hereditary Thrombotic Thrombocytopenic Purpura (TTP)
- What is being tested?
- Recombinant ADAMTS13
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 11 sitesin 7 countries
- Study dates
- 30 Sep 2014to 22 Feb 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Subject is between 12 and 65 years of age, inclusive. (The first 2 subjects in any cohort will be ≥ 18 years of age.)
- Subject and/or legally authorized representative has provided written informed consent.
- Subject has a documented diagnosis of severe hereditary ADAMTS13 deficiency, defined as 1) confirmed by genetic testing, documented in patient history or at screening, and 2) ADAMTS13 activity < 6%, documented in patient history or at screening. NOTE: In patients receiving prophylactic therapy with fresh frozen plasma (FFP) or other ADAMTS13 containing products, the levels of plasma ADAMTS13 activity may exceed 6% at screening.
- Cryoprecipitate, FFP, or other ADAMTS13 containing products interfering with ADAMTS13 PK have to be paused at least 10 days prior to infusion of the investigational product.
- The subject is not displaying any severe TTP symptoms at screening. Patients presenting with minor, but stable laboratory abnormalities (LDH not higher than 3 times the upper limit of normal; platelet count not lower than 100,000 per μl) at screening may be enrolled.
- Subjects ≥18 years of age have a Karnofsky score ≥ 60%, and subjects < 18 years of age have a Lansky score ≥ 70%.
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- Subject is hepatitis C virus negative (HCV-) as confirmed by antibody or polymerase chain reaction (PCR) testing; HCV positive (HCV+) subjects are eligible for inclusion if their disease is chronic but stable.
- 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.
- Subject is willing and able to comply with the requirements of the protocol.
Who cannot join
- Subject has been diagnosed with any other TTP-like disorder (for example, microangiopathic hemolytic anemia), including acquired TTP.
- Subject has known hypersensitivity to hamster proteins or other components of the investigational product.
- Subject has a medical history or presence of a functional neutralizing ADAMTS13 inhibitor at screening.
- Subject has a medical history of immunological disorders, excluding seasonal allergic rhinitis/conjunctivitis/mild asthma, food allergies or animal allergies.
- 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.
- 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.
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- Subject is HIV positive with an absolute CD4 count < 200/mm3.
- Subject has been diagnosed with a cardiovascular disease [New York Heart Association (NYHA) classes 3-4].
- Subject is scheduled to undergo elective surgery during study participation.
- 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, international normalized ratio (INR) > 1.5, hypoalbuminemia, portal vein hypertension (e.g. presence of otherwise unexplained splenomegaly, history of esophageal varices).
- Subject has been diagnosed with severe glomerular disease, with gross proteinuria and a serum creatinine level ≥ 2.5 mg/dL.
- Subject has been treated with an immunomodulatory drug, in case of corticoids with an equivalent to hydrocortisone greater than 10 mg /day, excluding topical treatment (e.g. ointments, nasal spray), within 30 days prior to enrollment.
- Subject has a history of drug and/or alcohol abuse within the last 6 months prior to study enrollment.
- Subject has a life expectancy of less than 3 months.
- Subject is identified by the investigator as being unable or unwilling to cooperate with study procedures.
- Subject is a family member or employee of the investigator.
- 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.
- If female, subject is pregnant or lactating at the time of study enrollment.
- Subject has participated in another clinical study involving an investigational product or device within 30 days prior to study enrollment.
- Subject is scheduled to participate in another clinical study involving an investigational product or device during the course of this study.
Trial locations and contacts
11 sites in 7 countries.
11 sites in 7 countries
United States3 sites
Ohio State University Medical Center
Dublin, Ohio, 43017
The Methodist Hospital Research Institute
Houston, Texas, 77030
Oregon Health & Science University
Portland, Oregon, 97239
Germany2 sites
Universitätsklinikum Hamburg-Eppendorf
Hamburg, 20246
Universitätsklinikum Jena
Jena, 07743
Japan2 sites
• Tokyo Medical and Dental University Hospital, Faculty of Medicine
Bunkyo-ku, Tokyo, 113-8519
Hyogo College of Medicine Hospital, Department of Hematology
Nishinomiya-shi, 663-8501
Austria1 site
General Hospital Vienna (Allgemeines Krankenhaus der Stadt Wien)
Vienna, 1090
United Kingdom1 site
University College London Hospital NHS Foundation Trust
London, NW1 2BU
About this study
Official title: BAX930 (rADAMTS13): A Phase 1 Prospective, Uncontrolled, Open-Label, Multicenter, Dose-Escalation Study Evaluating the Safety and Pharmacokinetics in Hereditary Thrombotic Thrombocytopenic Purpura (TTP)
The purpose of this Phase 1, prospective, uncontrolled, open-label, multicenter, dose-escalation study is to evaluate the safety, including immunogenicity, and pharmacokinetics of BAX930 (rADAMTS13) in a total of 14 evaluable subjects diagnosed with severe hereditary thrombotic thrombocytopenic purpura (TTP) (plasma ADAMTS13 activity <6%) who are assigned to one of three dose cohorts.
- Being tested
- Recombinant ADAMTS13
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Recombinant ADAMTS13Drug
rADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) is a lyophilized formulation for intravenous injection. The lyophilized rADAMTS13 is reconstituted with sterile water for injection.
Subjects will receive an intravenous injection with rADAMTS13 at a dose of either 5 U/kg bodyweight (Cohort 1), or 20 U/kg bodyweight (Cohort 2), or 40 U/kg bodyweight (Cohort 3).
| Study group | Role | What they receive |
|---|---|---|
| Recombinant ADAMTS13 | Experimental | The study is comprised of 3 dose cohorts and two dose escalation steps [Cohort 1: 3 subjects; Cohort 2: 3 subjects; Cohort 3: 8 subjects]. Subjects will be enrolled and dosed sequentially. Subjects will be recruited to the next dose level only after short-term safety has been demonstrated and reviewed by an independent Data Monitoring Committee (DMC) at the preceding dose level. The first 2 subjects in any cohort will be ≥ 18 years of age. The effects of the investigational product on vital signs, hematology, and clinical chemistry parameters (up to 96 ± 2 hrs blood sampling timepoint) will determine short-term safety. The DMC will recommend whether to proceed with the study or in case of a safety concern recommend remedial actions and/or to discontinue the study. Subject participation will continue until 28 ± 3 days after infusion of the investigational product. Subject participation in one Dose Cohort (1-3) is expected to be approximately 6-8 weeks. Receives: Drug: Recombinant ADAMTS13 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of adverse events (serious and non-serious), including the incidence of binding and inhibitory antibody formation
Measured: Up to 28 (± 3) days after investigational product infusion
Secondary outcomes (9)
Pharmacokinetic [PK] parameter 'incremental recovery [IR]'
Will be evaluated after single infusions of rADAMTS13 in Dose Cohorts 1, 2 and 3
Measured: Within 1 hour pre-infusion and up to 288 (± 4) hours post-infusion
PK parameter 'maximum concentration following infusion [Cmax]'
Will be evaluated after single infusions of rADAMTS13 in Dose Cohorts 1, 2 and 3
Measured: Within 1 hour pre-infusion and up to 288 (± 4) hours post-infusion
PK parameter 'minimum time to reach Cmax [T max]'
Will be evaluated after single infusions of rADAMTS13 in Dose Cohorts 1, 2 and 3
Measured: Within 1 hour pre-infusion and up to 288 (± 4) hours post-infusion
PK parameter 'terminal or disposition half-life [T1/2]'
Will be evaluated after single infusions of rADAMTS13 in Dose Cohorts 1, 2 and 3
Measured: Within 1 hour pre-infusion and up to 288 (± 4) hours post-infusion
PK parameter 'mean residence time [MRT]'
Will be evaluated after single infusions of rADAMTS13 in Dose Cohorts 1, 2 and 3
Measured: Within 1 hour pre-infusion and up to 288 (± 4) hours post-infusion
PK parameter 'systemic clearance [Cl]'
Will be evaluated after single infusions of rADAMTS13 in Dose Cohorts 1, 2 and 3
Measured: Within 1 hour pre-infusion and up to 288 (± 4) hours post-infusion
PK parameter 'area under the plasma/time curve [AUC]'
Will be evaluated after single infusions of rADAMTS13 in Dose Cohorts 1, 2 and 3
Measured: Within 1 hour pre-infusion and up to 288 (± 4) hours post-infusion
PK parameter 'steady state volume of distribution [Vss]'
Will be evaluated after single infusions of rADAMTS13 in Dose Cohorts 1, 2 and 3
Measured: Within 1 hour pre-infusion and up to 288 (± 4) hours post-infusion
Plasma von Willebrand factor: Ristocetin cofactor activity [VWF:RCo], von Willebrand factor antigen [VWF:Ag] and VWF structure analysis
Will be evaluated after single infusions of rADAMTS13 in Dose Cohorts 1, 2 and 3
Measured: Within 1 hour pre-infusion and up to 288 (± 4) hours post-infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2014 (estimated)
- Study start30 Sep 2014
- Primary completion22 Feb 2016
- Study completion22 Feb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hereditary Thrombotic Thrombocytopenic Purpura (TTP)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baxalta now part of Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02216084
- Sponsor's protocol ID
- 281101
- Other IDs
- 2012-003221-19
- Status last verified
- May 2021
- First submitted
- 12 Aug 2014
- Last updated
- 5 May 2021
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Scully M, Knobl P, Kentouche K, Rice L, Windyga J, Schneppenheim R, Kremer Hovinga JA, Kajiwara M, Fujimura Y, Maggiore C, Doralt J, Hibbard C, Martell L, Ewenstein B. Recombinant ADAMTS-13: first-in-human pharmacokinetics and safety in congenital thrombotic thrombocytopenic purpura. Blood. 2017 Nov 9;130(19):2055-2063. doi: 10.1182/blood-2017-06-788026. Epub 2017 Sep 14.
PubMed 28912376
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- BAX930 (rADAMTS13): A Phase 1 Prospective, Uncontrolled, Open-Label, Multicenter, Dose-Escalation Study Evaluating the Safety and Pharmacokinetics in Hereditary Thrombotic Thrombocytopenic Purpura (TTP)
- ClinicalTrials.gov ID
- NCT02216084
- Acronym / sponsor ID
- 281101
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Baxalta now part of ShireIndustry (pharma, biotech, devices)
- Study start
- 30 Sep 2014 (actual)
- Primary completion
- 22 Feb 2016 (actual)
- Study completion
- 22 Feb 2016 (actual)
- First posted
- 13 Aug 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this Phase 1, prospective, uncontrolled, open-label, multicenter, dose-escalation study is to evaluate the safety, including immunogenicity, and pharmacokinetics of BAX930 (rADAMTS13) in a total of 14 evaluable subjects diagnosed with severe hereditary thrombotic thrombocytopenic purpura (TTP) (plasma ADAMTS13 activity <6%) who are assigned to one of three dose cohorts.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Recombinant ADAMTS13 | Experimental | Drug: Recombinant ADAMTS13The study is comprised of 3 dose cohorts and two dose escalation steps [Cohort 1: 3 subjects; Cohort 2: 3 subjects; Cohort 3: 8 subjects]. Subjects will be enrolled and dosed sequentially. Subjects will be recruited to the next dose level only after short-term safety has been demonstrated and reviewed by an independent Data Monitoring Committee (DMC) at the preceding dose level. The first 2 subjects in any cohort will be ≥ 18 years of age. The effects of the investigational product on vital signs, hematology, and clinical chemistry parameters (up to 96 ± 2 hrs blood sampling timepoint) will determine short-term safety. The DMC will recommend whether to proceed with the study or in case of a safety concern recommend remedial actions and/or to discontinue the study. Subject participation will continue until 28 ± 3 days after infusion of the investigational product. Subject participation in one Dose Cohort (1-3) is expected to be approximately 6-8 weeks. |
Who may qualify
- Ages
- 12 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Subject is between 12 and 65 years of age, inclusive. (The first 2 subjects in any cohort will be ≥ 18 years of age.)
- Subject and/or legally authorized representative has provided written informed consent.
- Subject has a documented diagnosis of severe hereditary ADAMTS13 deficiency, defined as 1) confirmed by genetic testing, documented in patient history or at screening, and 2) ADAMTS13 activity < 6%, documented in patient history or at screening. NOTE: In patients receiving prophylactic therapy with fresh frozen plasma (FFP) or other ADAMTS13 containing products, the levels of plasma ADAMTS13 activity may exceed 6% at screening.
- Cryoprecipitate, FFP, or other ADAMTS13 containing products interfering with ADAMTS13 PK have to be paused at least 10 days prior to infusion of the investigational product.
- The subject is not displaying any severe TTP symptoms at screening. Patients presenting with minor, but stable laboratory abnormalities (LDH not higher than 3 times the upper limit of normal; platelet count not lower than 100,000 per μl) at screening may be enrolled.
Key exclusion criteria (20 listed)
- Subject has been diagnosed with any other TTP-like disorder (for example, microangiopathic hemolytic anemia), including acquired TTP.
- Subject has known hypersensitivity to hamster proteins or other components of the investigational product.
- Subject has a medical history or presence of a functional neutralizing ADAMTS13 inhibitor at screening.
- Subject has a medical history of immunological disorders, excluding seasonal allergic rhinitis/conjunctivitis/mild asthma, food allergies or animal allergies.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Recombinant ADAMTS13rADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) is a lyophilized formulation for intravenous injection. The lyophilized rADAMTS13 is reconstituted with sterile water for injection. Subjects will receive an intravenous injection with rADAMTS13 at a dose of either 5 U/kg bodyweight (Cohort 1), or 20 U/kg bodyweight (Cohort 2), or 40 U/kg bodyweight (Cohort 3). | Drug | Recombinant ADAMTS13 |
Primary outcome
Occurrence of adverse events (serious and non-serious), including the incidence of binding and inhibitory antibody formation
Time frame: Up to 28 (± 3) days after investigational product infusion
9 secondary outcomes
Pharmacokinetic [PK] parameter 'incremental recovery [IR]'
Time frame: Within 1 hour pre-infusion and up to 288 (± 4) hours post-infusion
PK parameter 'maximum concentration following infusion [Cmax]'
Time frame: Within 1 hour pre-infusion and up to 288 (± 4) hours post-infusion
PK parameter 'minimum time to reach Cmax [T max]'
Time frame: Within 1 hour pre-infusion and up to 288 (± 4) hours post-infusion
PK parameter 'terminal or disposition half-life [T1/2]'
Time frame: Within 1 hour pre-infusion and up to 288 (± 4) hours post-infusion
PK parameter 'mean residence time [MRT]'
Time frame: Within 1 hour pre-infusion and up to 288 (± 4) hours post-infusion
PK parameter 'systemic clearance [Cl]'
Time frame: Within 1 hour pre-infusion and up to 288 (± 4) hours post-infusion
PK parameter 'area under the plasma/time curve [AUC]'
Time frame: Within 1 hour pre-infusion and up to 288 (± 4) hours post-infusion
PK parameter 'steady state volume of distribution [Vss]'
Time frame: Within 1 hour pre-infusion and up to 288 (± 4) hours post-infusion
Plasma von Willebrand factor: Ristocetin cofactor activity [VWF:RCo], von Willebrand factor antigen [VWF:Ag] and VWF structure analysis
Time frame: Within 1 hour pre-infusion and up to 288 (± 4) hours post-infusion
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2021.
- Derived from this study: PubMed 28912376Scully M, Knobl P, Kentouche K, Rice L, Windyga J, Schneppenheim R, Kremer Hovinga JA, Kajiwara M, Fujimura Y, Maggiore C, Doralt J, Hibbard C, Martell L, Ewenstein B. Recombinant ADAMTS-13: first-in-human pharmacokinetics and safety in congenital thrombotic thrombocytopenic purpura. Blood. 2017 Nov 9;130(19):2055-2063. doi: 10.1182/blood-2017-06-788026. Epub 2017 Sep 14.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Takeda
11 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Recombinant ADAMTS13 in people with Hereditary Thrombotic Thrombocytopenic Purpura (TTP), run by Baxalta now part of Shire at 11 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, Germany, Japan, Austria, Poland and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Occurrence of adverse events (serious and non-serious), including the incidence of binding and inhibitory antibody formation (time frame: Up to 28 (± 3) days after investigational product infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02216084, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 May 2021; AzTrials last refreshed its copy on 26 Oct 2026.