Congenital Bleeding DisorderPhase 3mentor™4NCT01230021
Safety of a Single Intravenous Dose of Recombinant Factor XIII in Children With Congenital FXIII A-subunit Deficiency
A Phase 3 study testing catridecacog in people with Congenital Bleeding Disorder and Congenital FXIII Deficiency, run by Novo Nordisk A/S at 10 sites in 3 countries.
Trial summary
This trial is conducted in Europe and United States of America (USA). The aim of this clinical trial is to investigate the pharmacokinetics (at which rate the substance is distributed and eliminated from the body) and the safety profile of catridecacog (recombinant factor XIII (rFXIII)) in children with congenital… Read more about this study
- Who is it for?
- Ages 1 year to 6 years
- Conditions the study is for
- Congenital Bleeding Disorder, Congenital FXIII Deficiency
- What is being tested?
- catridecacog
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 10 sitesin 3 countries
- Study dates
- Nov 2010to Jan 2012
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 1 year to 6 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Signed Informed Consent by subject's parents or subject's legally acceptable representative before any trial related activities. Trial related activities are any procedures that would not have been performed during the normal management of the subject
- Age 1 to less than 6 years old at the time of enrolment
- Congenital FXIII subunit-A deficiency previously documented by genotyping or evaluated by genotyping through blood sampling at screening visit
- Body weight at least 10 kg
Who cannot join
- Known antibodies to FXIII
- Hereditary or acquired coagulation disorder other than FXIII A-subunit congenital deficiency
- Platelet count (thrombocytes) of less than 50 × 10^9/L (at screening visit)
- Previous history of autoimmune disorder involving autoantibodies e.g., systemic lupus erythematosus
- Previous history of arterial or venous thromboembolic events e.g., cerebrovascular accident or deep vein thrombosis
- Known or suspected allergy to trial product or related products
- Any surgical procedure in the 30 days prior to enrolment and any planned surgery during the trial period
- Any disease or condition which, judged by the Investigator, could imply a potential hazard to the subject or interfere with the trial participation or trial outcome including renal and/or liver dysfunction
Trial locations and contacts
10 sites in 3 countries.
10 sites in 3 countries
United Kingdom5 sites
Novo Nordisk Investigational Site
Birmingham, B4 6NH
Novo Nordisk Investigational Site
Leicester, LE1 5WW
Novo Nordisk Investigational Site
Manchester, M13 9WL
Novo Nordisk Investigational Site
Newcastle upon Tyne, NE1 4LP
Novo Nordisk Investigational Site
Reading, RG1 5AN
United States4 sites
Novo Nordisk Investigational Site
Boston, Massachusetts, 02115
Novo Nordisk Investigational Site
Columbus, Ohio, 43205
Novo Nordisk Investigational Site
Detroit, Michigan, 48201
Novo Nordisk Investigational Site
Minneapolis, Minnesota, 55404
About this study
Official title: A Phase 3b Trial Investigating the Pharmacokinetics and Safety Profile of a Single Intravenous Dose of rFXIII in Paediatric (1 to Less Than 6 Years Old) Subjects With Congenital FXIII A-subunit Deficiency
This trial is conducted in Europe and United States of America (USA). The aim of this clinical trial is to investigate the pharmacokinetics (at which rate the substance is distributed and eliminated from the body) and the safety profile of catridecacog (recombinant factor XIII (rFXIII)) in children with congenital FXIII A-subunit deficiency. Young children (1 to less than 6 years old) with congenital FXIII deficiency are evaluated.
- Being tested
- catridecacog
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
catridecacogDrug
Intravenous injection of a single dose of recombinant factor XIII, 35 IU/kg bodyweight
| Study group | Role | What they receive |
|---|---|---|
| recombinant factor XIII | Experimental | Not described Receives: Drug: catridecacog |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under the Concentration vs. Time Curve (AUC)
A measure of the exposure. Blood samples for the PK assessment were drawn pre-dose and up to 30 days after dosing. The PK of FXIII in children was assessed after a single i.v. dose of rFXIII 35 IU/kg.
Measured: At pre-dose, 30 minutes, 24 hours, 7, 14, 21 and 30 days after dosing
Secondary outcomes (16)
Area Under the Concentration vs. Time Curve (AUC0-∞)
A measure of exposure.
Measured: From day 0 to day 30
Maximum Plasma Concentration (Cmax) for FXIII
Maximum plasma concentration of the drug reached.
Measured: At pre-dose, 30 minutes, 24 hours, 7, 14, 21 and 30 days after dosing
Terminal Half-life (t½)
Time point when half of the maximum plasma concentration is reached.
Measured: From day 0 to day 30
Mean Residence Time (MRT)
The mean residence time (MRT) of a drug in the body and related functions are derived for drugs which are intravenously administered.
Measured: From day 0 to day 30
Total Plasma Clearance (CL)
The total plasma clearance is a measure of the elimination of a drug from the body. Drugs are excreted primarily by the kidneys into the urine. Clearance is calculated as 'CL=Dose / AUC0-30 days').
Measured: From day 0 to day 30
Volume of Distribution at Steady State (Vss)
Volume of distribution at steady state (Vss) is the theoretical volume that the total amount of administered drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it is in blood plasma at steady state. Steady state is achieved when all variables are constant in spite of ongoing processes.
Measured: At steady state
Percentage of Subjects With One or More Adverse Events (AEs) Recorded
Measured: From day 0 to day 30
Percentage of Subjects With One or More Serious Adverse Events (SAEs)
Measured: From day 0 to day 30
Percentage of Subjects With Development of Anti-rFXIII Antibodies, Including Inhibitors (Neutralising Antibodies Against Factor XIII)
Measured: At screening and day 30
Coagulation Related Parameters - Fibrinogen
Measured: Day 0 and at day 30
Coagulation Related Parameters - Activated Partial Thromboplastin Time (aPTT, Seconds)
Measured: Day 0 and day 30
Coagulation Related Parameters - Prothrombin Time (PT) (Seconds)
Measured: Day 0 and day 30
Clot Solubility Test (Evaluated as Normal/Abnormal)
Blood samples for clot solubility drawn at each visit (1 hour before and after dose administration). A clot solubility assay was used to screen for FXIII deficiency. The assay is based on the ability of urea to dissolve fibrin clots that have not undergone FXIII-induced stabilization. Normal blood clots generally remain stable for 24 hours or more, while clots in which fibrin molecules have not been cross-linked are soluble within minutes. The outcome of the test is normal (FXIII present; a clot is observed in the test tube) or abnormal (FXIII absent or very low level; no clot in test tube).
Measured: Day 0 and day 30
Vital Signs - Pulse
Measured: Day 0 and day 30
Vital Signs - Blood Pressure (Systolic and Diastolic)
Measured: Day 0 and day 30
Physical Examination (Evaluated as Normal/Abnormal)
Measured: From day 0 to day 30
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2010 (estimated)
- Study startNov 2010
- Primary completionJan 2012
- Study completionJan 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Congenital Bleeding DisorderStudies of the same condition, open and under way.
- More trials run by Novo Nordisk A/SThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novo Nordisk A/S
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Global Clinical Registry (GCR, 1452), Study director, Novo Nordisk A/S
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01230021
- Sponsor's protocol ID
- F13CD-3760
- Other IDs
- U1111-1116-2533, 2009-016869-28, 2009
- Acronym
- mentor™4
- Status last verified
- Jan 2017
- First submitted
- 27 Oct 2010
- Last updated
- 24 Feb 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Williams M, Will A, Stenmo C, Rosholm A, Tehranchi R. Pharmacokinetics of recombinant factor XIII in young children with congenital FXIII deficiency and comparison with older patients. Haemophilia. 2014 Jan;20(1):99-105. doi: 10.1111/hae.12224. Epub 2013 Jul 9.
PubMed 23834599Brand-Staufer B, Carcao M, Kerlin BA, Will A, Williams M, Tornoe CW, Sandberg Lundblad M, Nugent D. Pharmacokinetic characterization of recombinant factor XIII (FXIII)-A2 across age groups in patients with FXIII A-subunit congenital deficiency. Haemophilia. 2015 May;21(3):380-385. doi: 10.1111/hae.12616. Epub 2015 Jan 21.
PubMed 25643920
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3b Trial Investigating the Pharmacokinetics and Safety Profile of a Single Intravenous Dose of rFXIII in Paediatric (1 to Less Than 6 Years Old) Subjects With Congenital FXIII A-subunit Deficiency
- ClinicalTrials.gov ID
- NCT01230021
- Acronym / sponsor ID
- mentor™4 / F13CD-3760
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Novo Nordisk A/SIndustry (pharma, biotech, devices)
- Study start
- Nov 2010
- Primary completion
- Jan 2012 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 28 Oct 2010 (estimated)
- Results
- Posted 12 Jun 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial is conducted in Europe and United States of America (USA). The aim of this clinical trial is to investigate the pharmacokinetics (at which rate the substance is distributed and eliminated from the body) and the safety profile of catridecacog (recombinant factor XIII (rFXIII)) in children with congenital FXIII A-subunit deficiency. Young children (1 to less than 6 years old) with congenital FXIII deficiency are evaluated.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| recombinant factor XIII | Experimental | Drug: catridecacog |
Who may qualify
- Ages
- 1 year to 6 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Signed Informed Consent by subject's parents or subject's legally acceptable representative before any trial related activities. Trial related activities are any procedures that would not have been performed during the normal management of the subject
- Age 1 to less than 6 years old at the time of enrolment
- Congenital FXIII subunit-A deficiency previously documented by genotyping or evaluated by genotyping through blood sampling at screening visit
- Body weight at least 10 kg
Key exclusion criteria (8 listed)
- Known antibodies to FXIII
- Hereditary or acquired coagulation disorder other than FXIII A-subunit congenital deficiency
- Platelet count (thrombocytes) of less than 50 × 10^9/L (at screening visit)
- Previous history of autoimmune disorder involving autoantibodies e.g., systemic lupus erythematosus
- Previous history of arterial or venous thromboembolic events e.g., cerebrovascular accident or deep vein thrombosis
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 |
|---|---|---|
| catridecacogIntravenous injection of a single dose of recombinant factor XIII, 35 IU/kg bodyweight | Drug | recombinant factor XIII |
Primary outcome
Area Under the Concentration vs. Time Curve (AUC)
Time frame: At pre-dose, 30 minutes, 24 hours, 7, 14, 21 and 30 days after dosing
A measure of the exposure. Blood samples for the PK assessment were drawn pre-dose and up to 30 days after dosing. The PK of FXIII in children was assessed after a single i.v. dose of rFXIII 35 IU/kg.
16 secondary outcomes
Area Under the Concentration vs. Time Curve (AUC0-∞)
Time frame: From day 0 to day 30
Maximum Plasma Concentration (Cmax) for FXIII
Time frame: At pre-dose, 30 minutes, 24 hours, 7, 14, 21 and 30 days after dosing
Terminal Half-life (t½)
Time frame: From day 0 to day 30
Mean Residence Time (MRT)
Time frame: From day 0 to day 30
Total Plasma Clearance (CL)
Time frame: From day 0 to day 30
Volume of Distribution at Steady State (Vss)
Time frame: At steady state
Percentage of Subjects With One or More Adverse Events (AEs) Recorded
Time frame: From day 0 to day 30
Percentage of Subjects With One or More Serious Adverse Events (SAEs)
Time frame: From day 0 to day 30
Percentage of Subjects With Development of Anti-rFXIII Antibodies, Including Inhibitors (Neutralising Antibodies Against Factor XIII)
Time frame: At screening and day 30
Coagulation Related Parameters - Fibrinogen
Time frame: Day 0 and at day 30
Coagulation Related Parameters - Activated Partial Thromboplastin Time (aPTT, Seconds)
Time frame: Day 0 and day 30
Coagulation Related Parameters - Prothrombin Time (PT) (Seconds)
Time frame: Day 0 and day 30
Clot Solubility Test (Evaluated as Normal/Abnormal)
Time frame: Day 0 and day 30
Vital Signs - Pulse
Time frame: Day 0 and day 30
Vital Signs - Blood Pressure (Systolic and Diastolic)
Time frame: Day 0 and day 30
Physical Examination (Evaluated as Normal/Abnormal)
Time frame: From day 0 to day 30
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23834599Williams M, Will A, Stenmo C, Rosholm A, Tehranchi R. Pharmacokinetics of recombinant factor XIII in young children with congenital FXIII deficiency and comparison with older patients. Haemophilia. 2014 Jan;20(1):99-105. doi: 10.1111/hae.12224. Epub 2013 Jul 9.
- Results publication: PubMed 25643920Brand-Staufer B, Carcao M, Kerlin BA, Will A, Williams M, Tornoe CW, Sandberg Lundblad M, Nugent D. Pharmacokinetic characterization of recombinant factor XIII (FXIII)-A2 across age groups in patients with FXIII A-subunit congenital deficiency. Haemophilia. 2015 May;21(3):380-385. doi: 10.1111/hae.12616. Epub 2015 Jan 21.
- Clinical Trials at Novo NordiskLink provided by the sponsor.
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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.
Global Clinical Registry (GCR, 1452) study director
Novo Nordisk A/S
10 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing catridecacog in people with Congenital Bleeding Disorder and Congenital FXIII Deficiency, run by Novo Nordisk A/S at 10 sites in 3 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 4 inclusion and 8 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 24 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United Kingdom, United States, Israel. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jun 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Area Under the Concentration vs. Time Curve (AUC) (time frame: At pre-dose, 30 minutes, 24 hours, 7, 14, 21 and 30 days after dosing). 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 NCT01230021, which also lists 2 linked publications.
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 24 Feb 2017.