Inflammation, Ulcerative Colitis
Conditions
Brief summary
This trial is conducted in Europe. The aim of the trial is to investigate the effect of recombinant factor XIII (rFXIII) administered to subjects with mild to moderate active ulcerative colitis (UC).
Interventions
DRUGcatridecacog
Catridecacog (recombinant factor XIII, rFXIII) will be administered as intravenous (i.v.) injections (at an approximate rate of 1-2 mL/min) once every second week at a dose of 35 IU/kg
DRUGplacebo
Placebo will be administered as intravenous (i.v.) injections (at an approximate rate of 1-2 mL/min) once every second week.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of ulcerative colitis for at least 3 months from the time of initial diagnosis. The diagnosis must have been confirmed by historical endoscopy and histology. The severity of disease must have been confirmed by endoscopy at screening * Currently receiving oral aminosalicylates at approved doses of at least 2g/day for at least 6 weeks. Doses of oral aminosalicylates should be stable for at least two weeks prior to dosing (Visit 2)
Exclusion criteria
* Diagnosis of UC limited to the rectum (ulcerative proctitis only, defined as less than 15 cm from the anal verge) * Requiring hospitalisation for current episode of severe UC * Use of biologic therapies for the treatment of UC within 12 weeks prior to dosing (Visit 2) * Treatment failures to anti-tumour necrosis factor-alfa (anti-TNF-a) agents (e.g. infliximab, adalimumab) * Use of immunosuppressant agents (e.g. azathioprine) within 4 weeks prior to dosing (Visit 2) * Use of corticosteroids (oral, intravenous (i.v.), intramuscular (i.m.), or rectal ) within 14 days prior to dosing (Visit 2) * Use of enemas (corticosteroid or aminosalicylate) within 14 days prior to screening (Visit 1) * Use of cyclosporine, tacrolimus, D-penicillamine, leflunomide, methotrexate, mycophenolate mofetil, or thalidomide within 4 weeks prior to dosing (Visit 2) * Currently receiving total parenteral nutrition
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Endoscopic Remission Defined as a Modified Baron Score of 0 | At week 8 | The primary endpoint was the binary variable (responder vs. non-responder) where responders were the subjects with endoscopic remission (endoscopic mucosal healing) at Week 8, defined as a modified Baron score of 0. Subjects with a modified Baron score ≥1 were designated as non-responders. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Remission (Clinical and Endoscopic) | At Week 8 | Analysis of responders defined by a clinical component of: ulcerative colitis disease activity index (UC-DAI) score of less than or equal to 1 with 0 for rectal bleeding and 0 for stool frequency and an endoscopic component of: no mucosal friability (modified Baron score less than or equal to 1). |
| Number of Adverse Events (AEs) | Week 0 to 10 | Number of adverse events reported from the first trial-related activity, after the subject was exposed to the trial drug, until the end of the post-treatment follow-up period. |
| Clearance (CL) of rFXIII | Samples were collected before and up to 72 hours after the first dose of rFXIII. | The volume of plasma cleared of the drug per unit time. |
| Maximum Concentration (Cmax) of rFXIII | Samples were collected before and up to 72 hours after the first dose of rFXIII. | The peak plasma concentration of the drug after dose administration. |
Countries
Bulgaria, Croatia, Denmark, Hungary, Poland, Russia, Ukraine
Participant flow
Recruitment details
The trial was conducted at 12 sites in 6 countries as follows: Bulgaria (4 sites), Denmark (1 site), Hungary (1 site), Poland (4 sites), Russian Federation (1 site) and Ukraine (1 site).
Pre-assignment details
No pre-assignments were given for this trial.
Participants by arm
| Arm | Count |
|---|---|
| rFXIII Recombinant factor XIII (rFXIII) was administered as intravenous (i.v.) injections (at an approximate rate of 1-2 mL/min) at a dose of 35 IU/kg. The doses were administered once every second week for a total of 4 doses. | 13 |
| Placebo Placebo formulation was administered as intravenous (i.v.) injections (at an approximate rate of 1-2 mL/min) once every second week. The doses were administered for a total of 4 doses. | 5 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Unclassified | 6 | 1 |
| Overall Study | Withdrawal Criteria | 2 | 1 |
Baseline characteristics
| Characteristic | rFXIII | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 36.9 years STANDARD_DEVIATION 10.6 | 45.0 years STANDARD_DEVIATION 15.4 | 39.2 years STANDARD_DEVIATION 12.2 |
| Body Mass Index | 24.5 kg/m^2 STANDARD_DEVIATION 3.2 | 25.6 kg/m^2 STANDARD_DEVIATION 5.8 | 24.8 kg/m^2 STANDARD_DEVIATION 3.9 |
| Race/Ethnicity, Customized Whites | 13 participants | 5 participants | 18 participants |
| Sex: Female, Male Female | 5 Participants | 4 Participants | 9 Participants |
| Sex: Female, Male Male | 8 Participants | 1 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 13 | 2 / 5 |
| serious Total, serious adverse events | 1 / 13 | 0 / 5 |
Outcome results
Primary
Endoscopic Remission Defined as a Modified Baron Score of 0
The primary endpoint was the binary variable (responder vs. non-responder) where responders were the subjects with endoscopic remission (endoscopic mucosal healing) at Week 8, defined as a modified Baron score of 0. Subjects with a modified Baron score ≥1 were designated as non-responders.
Time frame: At week 8
Population: Full analysis set (FAS) included all randomised and treated subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| rFXIII | Endoscopic Remission Defined as a Modified Baron Score of 0 | 1 Subjects |
| Placebo | Endoscopic Remission Defined as a Modified Baron Score of 0 | 1 Subjects |
Comparison: A sample size of 90 subjects, with a 2:1 (active:placebo) randomization ratio, would ensure 80% power to detect a difference between active treatment and placebo at Week 8 with a 2-sided significance level of 10% based on a Fisher's exact test.p-value: 0.305690% CI: [0.01, 3.05]Regression, Logistic
Secondary
Clearance (CL) of rFXIII
The volume of plasma cleared of the drug per unit time.
Time frame: Samples were collected before and up to 72 hours after the first dose of rFXIII.
Population: It was not possible to obtain credible single dose pharmakokinetics (PK) for rFXIII in this trial due to a small number of subjects with required PK measurements and a spurious behaviour of individual PK profiles.
Secondary
Maximum Concentration (Cmax) of rFXIII
The peak plasma concentration of the drug after dose administration.
Time frame: Samples were collected before and up to 72 hours after the first dose of rFXIII.
Population: It was not possible to obtain credible single dose PK for rFXIII in this trial due to a small number of subjects with required PK measurements and a spurious behaviour of individual PK profiles.
Secondary
Number of Adverse Events (AEs)
Number of adverse events reported from the first trial-related activity, after the subject was exposed to the trial drug, until the end of the post-treatment follow-up period.
Time frame: Week 0 to 10
Population: Safety analysis set included all randomised and treated subjects.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| rFXIII | Number of Adverse Events (AEs) | Adverse events | 7 events |
| rFXIII | Number of Adverse Events (AEs) | Serious adverse events | 1 events |
| rFXIII | Number of Adverse Events (AEs) | Severe adverse events | 1 events |
| rFXIII | Number of Adverse Events (AEs) | Moderate adverse events | 0 events |
| rFXIII | Number of Adverse Events (AEs) | Mild adverse events | 6 events |
| rFXIII | Number of Adverse Events (AEs) | Fatal adverse events | 0 events |
| Placebo | Number of Adverse Events (AEs) | Mild adverse events | 2 events |
| Placebo | Number of Adverse Events (AEs) | Adverse events | 4 events |
| Placebo | Number of Adverse Events (AEs) | Moderate adverse events | 2 events |
| Placebo | Number of Adverse Events (AEs) | Serious adverse events | 0 events |
| Placebo | Number of Adverse Events (AEs) | Fatal adverse events | 0 events |
| Placebo | Number of Adverse Events (AEs) | Severe adverse events | 0 events |
Secondary
Remission (Clinical and Endoscopic)
Analysis of responders defined by a clinical component of: ulcerative colitis disease activity index (UC-DAI) score of less than or equal to 1 with 0 for rectal bleeding and 0 for stool frequency and an endoscopic component of: no mucosal friability (modified Baron score less than or equal to 1).
Time frame: At Week 8
Population: Full analysis set (FAS) included all randomised and treated subjects. Two subjects in the rFXIII group had no UC-DAI score at any visit, including baseline and they were excluded from the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| rFXIII | Remission (Clinical and Endoscopic) | 0 Subjects |
| Placebo | Remission (Clinical and Endoscopic) | 0 Subjects |