Clinical Trial Results:
A MULTICENTER, SUBJECT-BLIND, INVESTIGATOR-BLIND, RANDOMIZED, PLACEBO-CONTROLLED STUDY EVALUATING THE EFFICACY, SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF AN IV LOADING DOSE FOLLOWED BY SC ADMINISTRATION OF BIMEKIZUMAB (UCB4940) IN SUBJECTS WITH MODERATE TO SEVERE ACTIVE ULCERATIVE COLITIS
|
Summary
|
|
EudraCT number |
2016-000420-26 |
Trial protocol |
CZ ES PL BG |
Global end of trial date |
30 May 2018
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
13 Jun 2019
|
First version publication date |
13 Jun 2019
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
UC0011
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
UCB Biopharma SPRL
|
||
Sponsor organisation address |
Allée de la Recherche 60, Brussels, Belgium, 1070
|
||
Public contact |
Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com
|
||
Scientific contact |
Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
28 Jun 2018
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
30 May 2018
|
||
Was the trial ended prematurely? |
Yes
|
||
|
General information about the trial
|
|||
Main objective of the trial |
To assess the efficacy of bimekizumab in adults with active ulcerative colitis who have not responded to standard therapy.
|
||
Protection of trial subjects |
During the conduct of the study all subjects were closely monitored
|
||
Background therapy |
Background therapy as permitted in the protocol | ||
Evidence for comparator |
Not applicable | ||
Actual start date of recruitment |
01 Nov 2016
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Czech Republic: 1
|
||
Country: Number of subjects enrolled |
Georgia: 7
|
||
Country: Number of subjects enrolled |
Italy: 1
|
||
Country: Number of subjects enrolled |
Moldova, Republic of: 7
|
||
Country: Number of subjects enrolled |
Poland: 1
|
||
Country: Number of subjects enrolled |
Romania: 1
|
||
Country: Number of subjects enrolled |
South Africa: 4
|
||
Country: Number of subjects enrolled |
Spain: 1
|
||
Worldwide total number of subjects |
23
|
||
EEA total number of subjects |
5
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
23
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
||
|
|||||||||||||||||||||||||
|
Recruitment
|
|||||||||||||||||||||||||
Recruitment details |
The study started to enroll patients in November 2016 and concluded in May 2018. | ||||||||||||||||||||||||
|
Pre-assignment
|
|||||||||||||||||||||||||
Screening details |
The Participant Flow refers to the Randomized Set. | ||||||||||||||||||||||||
|
Period 1
|
|||||||||||||||||||||||||
Period 1 title |
Overall Study (overall period)
|
||||||||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Randomised - controlled
|
||||||||||||||||||||||||
Blinding used |
Double blind | ||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Carer, Assessor | ||||||||||||||||||||||||
|
Arms
|
|||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
||||||||||||||||||||||||
|
Arm title
|
Placebo | ||||||||||||||||||||||||
Arm description |
Subjects were administered one dose of intravenous (iv) placebo infusion at Visit 2 (Day 1) and 2 doses of subcutaneous placebo (sc) injections at Visit 3 (Day 22 ± 2 days) and Visit 4 (Day 43 ± 2 days). | ||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
|
||||||||||||||||||||||||
Investigational medicinal product code |
PBO
|
||||||||||||||||||||||||
Other name |
PBO
|
||||||||||||||||||||||||
Pharmaceutical forms |
Infusion, Injection
|
||||||||||||||||||||||||
Routes of administration |
Intravenous use, Subcutaneous use
|
||||||||||||||||||||||||
Dosage and administration details |
Placebo given as an iv infusion at Visit 2 (Day 1) and placebo given as a sc injection at Visit 3 (Day 22 ± 2 days) and Visit 4 (Day 43 ± 2 days).
|
||||||||||||||||||||||||
|
Arm title
|
BKZ 560/420 mg | ||||||||||||||||||||||||
Arm description |
Subjects were administered 560 mg of bimekizumab (BKZ) iv infusion at Visit 2 (Day 1) and 2 doses of 420 mg sc BKZ injections at Visit 3 (Day 22 ± 2 days) and Visit 4 (Day 43 ± 2 days). | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Bimekizumab
|
||||||||||||||||||||||||
Investigational medicinal product code |
UCB4940
|
||||||||||||||||||||||||
Other name |
BKZ
|
||||||||||||||||||||||||
Pharmaceutical forms |
Infusion, Injection
|
||||||||||||||||||||||||
Routes of administration |
Intravenous use, Subcutaneous use
|
||||||||||||||||||||||||
Dosage and administration details |
560 mg of bimekizumab (BKZ) given as a loading dose iv infusion at Visit 2 (Day 1) followed by 420 mg BKZ given by sc injection at Visit 3 (Day 22 ± 2 days) and Visit 4 (Day 43 ± 2 days).
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects were administered one dose of intravenous (iv) placebo infusion at Visit 2 (Day 1) and 2 doses of subcutaneous placebo (sc) injections at Visit 3 (Day 22 ± 2 days) and Visit 4 (Day 43 ± 2 days). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
BKZ 560/420 mg
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects were administered 560 mg of bimekizumab (BKZ) iv infusion at Visit 2 (Day 1) and 2 doses of 420 mg sc BKZ injections at Visit 3 (Day 22 ± 2 days) and Visit 4 (Day 43 ± 2 days). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Subject analysis sets
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Placebo (FAS)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Subjects were administered one dose of intravenous (iv) placebo infusion at Visit 2 (Day 1) and 2 doses of subcutaneous placebo (sc) injections at Visit 3 (Day 22 ± 2 days) and Visit 4 (Day 43 ± 2 days), forming the Full Analysis Set (FAS).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
BKZ 560/420 mg (FAS)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Subjects were administered 560 mg of bimekizumab (BKZ) iv infusion at Visit 2 (Day 1) and 2 doses of 420 mg sc BKZ injections at Visit 3 (Day 22 ± 2 days) and Visit 4 (Day 43 ± 2 days), forming the FAS.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Placebo (SS)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Subjects were administered one dose of intravenous (iv) placebo infusion at Visit 2 (Day 1) and 2 doses of subcutaneous placebo (sc) injections at Visit 3 (Day 22 ± 2 days) and Visit 4 (Day 43 ± 2 days), forming the Safety Set (SS).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
BKZ 560/420 mg (SS)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Subjects were administered 560 mg of bimekizumab (BKZ) iv infusion at Visit 2 (Day 1) and 2
doses of 420 mg sc BKZ injections at Visit 3 (Day 22 ± 2 days) and Visit 4 (Day 43 ± 2 days),
forming the SS.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
BKZ 560/420 mg (PK-PPS)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Subjects were administered 560 mg of bimekizumab (BKZ) iv infusion at Visit 2 (Day 1) and 2
doses of 420 mg sc BKZ injections at Visit 3 (Day 22 ± 2 days) and Visit 4 (Day 43 ± 2 days),
forming the Pharmacokinetic-Per Protocol Set (PK-PPS).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Placebo
|
||
Reporting group description |
Subjects were administered one dose of intravenous (iv) placebo infusion at Visit 2 (Day 1) and 2 doses of subcutaneous placebo (sc) injections at Visit 3 (Day 22 ± 2 days) and Visit 4 (Day 43 ± 2 days). | ||
Reporting group title |
BKZ 560/420 mg
|
||
Reporting group description |
Subjects were administered 560 mg of bimekizumab (BKZ) iv infusion at Visit 2 (Day 1) and 2 doses of 420 mg sc BKZ injections at Visit 3 (Day 22 ± 2 days) and Visit 4 (Day 43 ± 2 days). | ||
Subject analysis set title |
Placebo (FAS)
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Subjects were administered one dose of intravenous (iv) placebo infusion at Visit 2 (Day 1) and 2 doses of subcutaneous placebo (sc) injections at Visit 3 (Day 22 ± 2 days) and Visit 4 (Day 43 ± 2 days), forming the Full Analysis Set (FAS).
|
||
Subject analysis set title |
BKZ 560/420 mg (FAS)
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Subjects were administered 560 mg of bimekizumab (BKZ) iv infusion at Visit 2 (Day 1) and 2 doses of 420 mg sc BKZ injections at Visit 3 (Day 22 ± 2 days) and Visit 4 (Day 43 ± 2 days), forming the FAS.
|
||
Subject analysis set title |
Placebo (SS)
|
||
Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Subjects were administered one dose of intravenous (iv) placebo infusion at Visit 2 (Day 1) and 2 doses of subcutaneous placebo (sc) injections at Visit 3 (Day 22 ± 2 days) and Visit 4 (Day 43 ± 2 days), forming the Safety Set (SS).
|
||
Subject analysis set title |
BKZ 560/420 mg (SS)
|
||
Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Subjects were administered 560 mg of bimekizumab (BKZ) iv infusion at Visit 2 (Day 1) and 2
doses of 420 mg sc BKZ injections at Visit 3 (Day 22 ± 2 days) and Visit 4 (Day 43 ± 2 days),
forming the SS.
|
||
Subject analysis set title |
BKZ 560/420 mg (PK-PPS)
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Subjects were administered 560 mg of bimekizumab (BKZ) iv infusion at Visit 2 (Day 1) and 2
doses of 420 mg sc BKZ injections at Visit 3 (Day 22 ± 2 days) and Visit 4 (Day 43 ± 2 days),
forming the Pharmacokinetic-Per Protocol Set (PK-PPS).
|
||
|
|||||||||||||
End point title |
Percentage of Participants with Clinical Response (Per Mayo Score) at Week 8 [1] | ||||||||||||
End point description |
Clinical Response achieved at Week 8 is defined as a decrease from Baseline in Total Mayo Score of at least 3 points and at least 30 percent (%), with an accompanying decrease in the subscore for Rectal Bleeding of at least 1 point or absolute subscore for Rectal Bleeding of 0 (no blood seen) or 1 (streaks of blood with stool less than half the time). The rectal bleeding score ranges from 0 (no blood seen) to 3 (blood alone passes).
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
At Week 8
|
||||||||||||
| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Given the lack of Week 8 data, expected at the end of the study (and lack of subjects completing the required dosing regimen), a decision has been made that none of the planned Bayesian analyses would be performed, as they would lack validity, given the data that would be available at the end of the study. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percentage of participants with Adverse Events throughout the study conduct up to Week 20 [2] | ||||||||||||
End point description |
An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Up to Week 20
|
||||||||||||
| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Given the lack of Week 8 data, expected at the end of the study (and lack of subjects completing the required dosing regimen), a decision has been made that none of the planned Bayesian analyses would be performed, as they would lack validity, given the data that would be available at the end of the study. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percentage of Participants in Clinical Remission at Week 8 | ||||||||||||
End point description |
Clinical Remission achieved at Week 8 is defined as a Total Mayo Score of lower than or equal to (<=) 2 points, with no individual subscore higher than (>) 1 point. The Mayo score ranges from 0 to 12, with higher scores indicating more severe disease.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
At Week 8
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percentage of Participants with Mucosal Healing at Week 8 | ||||||||||||
End point description |
Mucosal Healing achieved at Week 8 is defined as an Endoscopic subscore of <=1 point. The endoscopic scores ranges from 0 (normal or inactive disease) to 3 (severe disease).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
At Week 8
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percentage of Participants With Stool Frequency Subscore Indicative of Mild Disease (a Score of 0 or 1) at Week 8 | ||||||||||||
End point description |
A score of 0 on the Stool Frequency Subscore indicates normal numbers of stools for the patient per day, while a score of 1 on the Stool Frequency Subscore indicates 1 or 2 stools more than usual.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
At Week 8
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percentage of Participants With Physician's Global Assessment Subscore Indicative of Mild Disease (a Score of 0 or 1) at Week 8 | ||||||||||||
End point description |
A score of 0 on the PGA Subscore indicates normal disease, while a score of 1 on the PGA Subscore indicates mild disease.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
At Week 8
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percentage of Participants With Rectal Bleeding Subscore Indicative of Mild Disease (a Score of 0 or 1) at Week 8 | ||||||||||||
End point description |
A score of 0 on the Rectal Bleeding Subscore indicates no blood seen, while a score of 1 on the Rectal Bleeding Subscore indicates streaks of blood with stool less than half the time.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
At Week 8
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Change from Baseline in C-reactive protein (CRP) plasma level at Week 8 | ||||||||||||
End point description |
Baseline for CRP was considered Day 1, predose, or if Day 1 measurement was missing, the Screening value was considered Baseline.
CRP, measurements that are below the limit of quantification (BLQ) were imputed with half of the lower limit of quantification (LLOQ) for the purpose of calculating changes from Baseline. Measurements above the upper limit of quantification (ALQ), were imputed to the upper quantification limit.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
At Week 8
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||
End point title |
Plasma concentration of Bimekizumab (BKZ) over time - at Day 1, prior to dosing | ||||||||
End point description |
BKZ plasma concentration was expressed as geometric mean concentration and measure in nanograms per milillitre (ng/mL).
Note 1: Values Bellow Limit of Quantification (BLQ) are replaced by value of Lower Limit Of Quantification (LLOQ)/2 (=75ng/mL) in calculations of descriptive statistics.
Note 2: Descriptive statistics were only calculated if at least 2/3 of the concentrations were quantified at the respective timepoint.
Note 3: At Day 1, Pre-dose, the BKZ concentrations were not available.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Day 1 sampling for PK evaluation was done: predose (1h prior dosing), 1h (post infusion), and 5h (±1h). At Day 22, 43 blood sampling was done prior dosing, at 1.5 and 5 hours after dosing. From Day 57 to Day 183, a single sample was collected.
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Plasma concentration of Bimekizumab (BKZ) over time - at Day 1, 1 hour after dosing | ||||||||
End point description |
BKZ plasma concentration was expressed as geometric mean concentration and measure in nanograms per milillitre (ng/mL).
Note 1: Values Bellow Limit of Quantification (BLQ) are replaced by value of Lower Limit Of Quantification (LLOQ)/2 (=75ng/mL) in calculations of descriptive statistics.
Note 2: Descriptive statistics were only calculated if at least 2/3 of the concentrations were quantified at the respective timepoint.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Day 1 sampling for PK evaluation was done: predose (1h prior dosing), 1h (post infusion), and 5h (±1h). At Day 22, 43 blood sampling was done prior dosing, at 1.5 and 5 hours after dosing. From Day 57 to Day 183, a single sample was collected.
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Plasma concentration of Bimekizumab (BKZ) over time - at Day 1, 5 hours after dosing | ||||||||
End point description |
BKZ plasma concentration was expressed as geometric mean concentration and measure in nanograms per milillitre (ng/mL).
Note 1: Values Bellow Limit of Quantification (BLQ) are replaced by value of Lower Limit Of Quantification (LLOQ)/2 (=75ng/mL) in calculations of descriptive statistics.
Note 2: Descriptive statistics were only calculated if at least 2/3 of the concentrations were quantified at the respective timepoint.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Day 1 sampling for PK evaluation was done: predose (1h prior dosing), 1h (post infusion), and 5h (±1h). At Day 22, 43 blood sampling was done prior dosing, at 1.5 and 5 hours after dosing. From Day 57 to Day 183, a single sample was collected.
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Plasma concentration of Bimekizumab (BKZ) over time - at Day 22, Pre-dose | ||||||||
End point description |
BKZ plasma concentration was expressed as geometric mean concentration and measure in nanograms per milillitre (ng/mL).
Note 1: Values Bellow Limit of Quantification (BLQ) are replaced by value of Lower Limit Of Quantification (LLOQ)/2 (=75ng/mL) in calculations of descriptive statistics.
Note 2: Descriptive statistics were only calculated if at least 2/3 of the concentrations were quantified at the respective timepoint.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Day 1 sampling for PK evaluation was done: predose (1h prior dosing), 1h (post infusion), and 5h (±1h). At Day 22, 43 blood sampling was done prior dosing, at 1.5 and 5 hours after dosing. From Day 57 to Day 183, a single sample was collected.
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Plasma concentration of Bimekizumab (BKZ) over time - at Day 22, 1.5 hours after dosing | ||||||||
End point description |
BKZ plasma concentration was expressed as geometric mean concentration and measure in nanograms per milillitre (ng/mL).
Note 1: Values Bellow Limit of Quantification (BLQ) are replaced by value of Lower Limit Of Quantification (LLOQ)/2 (=75ng/mL) in calculations of descriptive statistics.
Note 2: Descriptive statistics were only calculated if at least 2/3 of the concentrations were quantified at the respective timepoint.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Day 1 sampling for PK evaluation was done: predose (1h prior dosing), 1h (post infusion), and 5h (±1h). At Day 22, 43 blood sampling was done prior dosing, at 1.5 and 5 hours after dosing. From Day 57 to Day 183, a single sample was collected.
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Plasma concentration of Bimekizumab (BKZ) over time - at Day 22, 5 hours after dosing | ||||||||
End point description |
BKZ plasma concentration was expressed as geometric mean concentration and measure in nanograms per milillitre (ng/mL).
Note 1: Values Bellow Limit of Quantification (BLQ) are replaced by value of Lower Limit Of Quantification (LLOQ)/2 (=75ng/mL) in calculations of descriptive statistics.
Note 2: Descriptive statistics were only calculated if at least 2/3 of the concentrations were quantified at the respective timepoint.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Day 1 sampling for PK evaluation was done: predose (1h prior dosing), 1h (post infusion), and 5h (±1h). At Day 22, 43 blood sampling was done prior dosing, at 1.5 and 5 hours after dosing. From Day 57 to Day 183, a single sample was collected.
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Plasma concentration of Bimekizumab (BKZ) over time - at Day 43, Pre-dose | ||||||||
End point description |
BKZ plasma concentration was expressed as geometric mean concentration and measure in nanograms per milillitre (ng/mL).
Note 1: Values Bellow Limit of Quantification (BLQ) are replaced by value of Lower Limit Of Quantification (LLOQ)/2 (=75ng/mL) in calculations of descriptive statistics.
Note 2: Descriptive statistics were only calculated if at least 2/3 of the concentrations were quantified at the respective timepoint.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Day 1 sampling for PK evaluation was done: predose (1h prior dosing), 1h (post infusion), and 5h (±1h). At Day 22, 43 blood sampling was done prior dosing, at 1.5 and 5 hours after dosing. From Day 57 to Day 183, a single sample was collected.
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Plasma concentration of Bimekizumab (BKZ) over time - at Day 43, 1.5 hours after dosing | ||||||||
End point description |
BKZ plasma concentration was expressed as geometric mean concentration and measure in nanograms per milillitre (ng/mL).
Note 1: Values Bellow Limit of Quantification (BLQ) are replaced by value of Lower Limit Of Quantification (LLOQ)/2 (=75ng/mL) in calculations of descriptive statistics.
Note 2: Descriptive statistics were only calculated if at least 2/3 of the concentrations were quantified at the respective timepoint.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Day 1 sampling for PK evaluation was done: predose (1h prior dosing), 1h (post infusion), and 5h (±1h). At Day 22, 43 blood sampling was done prior dosing, at 1.5 and 5 hours after dosing. From Day 57 to Day 183, a single sample was collected.
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Plasma concentration of Bimekizumab (BKZ) over time - at Day 43, 5 hours after dosing | ||||||||
End point description |
BKZ plasma concentration was expressed as geometric mean concentration and measure in nanograms per milillitre (ng/mL).
Note 1: Values Bellow Limit of Quantification (BLQ) are replaced by value of Lower Limit Of Quantification (LLOQ)/2 (=75ng/mL) in calculations of descriptive statistics.
Note 2: Descriptive statistics were only calculated if at least 2/3 of the concentrations were quantified at the respective timepoint.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Day 1 sampling for PK evaluation was done: predose (1h prior dosing), 1h (post infusion), and 5h (±1h). At Day 22, 43 blood sampling was done prior dosing, at 1.5 and 5 hours after dosing. From Day 57 to Day 183, a single sample was collected.
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Plasma concentration of Bimekizumab (BKZ) over time - at Day 57 | ||||||||
End point description |
BKZ plasma concentration was expressed as geometric mean concentration and measure in nanograms per milillitre (ng/mL).
Note 1: Values Bellow Limit of Quantification (BLQ) are replaced by value of Lower Limit Of Quantification (LLOQ)/2 (=75ng/mL) in calculations of descriptive statistics.
Note 2: Descriptive statistics were only calculated if at least 2/3 of the concentrations were quantified at the respective timepoint.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Day 1 sampling for PK evaluation was done: predose (1h prior dosing), 1h (post infusion), and 5h (±1h). At Day 22, 43 blood sampling was done prior dosing, at 1.5 and 5 hours after dosing. From Day 57 to Day 183, a single sample was collected.
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Plasma concentration of Bimekizumab (BKZ) over time - at Day 85 | ||||||||
End point description |
BKZ plasma concentration was expressed as geometric mean concentration and measure in nanograms per milillitre (ng/mL).
Note 1: Values Bellow Limit of Quantification (BLQ) are replaced by value of Lower Limit Of Quantification (LLOQ)/2 (=75ng/mL) in calculations of descriptive statistics.
Note 2: Descriptive statistics were only calculated if at least 2/3 of the concentrations were quantified at the respective timepoint.
Note 3: Due to low number of subjects (N = 1), Geometric Mean could not be calculated and a placeholder value '999' was used instead, for technical reasons.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Day 1 sampling for PK evaluation was done: predose (1h prior dosing), 1h (post infusion), and 5h (±1h). At Day 22, 43 blood sampling was done prior dosing, at 1.5 and 5 hours after dosing. From Day 57 to Day 183, a single sample was collected.
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Plasma concentration of Bimekizumab (BKZ) over time - at Day 99 | ||||||||
End point description |
BKZ plasma concentration was expressed as geometric mean concentration and measure in nanograms per milillitre (ng/mL).
Note 1: Values Bellow Limit of Quantification (BLQ) are replaced by value of Lower Limit Of Quantification (LLOQ)/2 (=75ng/mL) in calculations of descriptive statistics.
Note 2: Descriptive statistics were only calculated if at least 2/3 of the concentrations were quantified at the respective timepoint.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Day 1 sampling for PK evaluation was done: predose (1h prior dosing), 1h (post infusion), and 5h (±1h). At Day 22, 43 blood sampling was done prior dosing, at 1.5 and 5 hours after dosing. From Day 57 to Day 183, a single sample was collected.
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Plasma concentration of Bimekizumab (BKZ) over time - at Day 141 | ||||||||
End point description |
BKZ plasma concentration was expressed as geometric mean concentration and measure in nanograms per milillitre (ng/mL).
Note 1: Values Bellow Limit of Quantification (BLQ) are replaced by value of Lower Limit Of Quantification (LLOQ)/2 (=75ng/mL) in calculations of descriptive statistics.
Note 2: Descriptive statistics were only calculated if at least 2/3 of the concentrations were quantified at the respective timepoint.
Note 3: Due to low number of subjects (N = 1), Geometric Mean could not be calculated and a placeholder value '999' was used instead, for technical reasons.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Day 1 sampling for PK evaluation was done: predose (1h prior dosing), 1h (post infusion), and 5h (±1h). At Day 22, 43 blood sampling was done prior dosing, at 1.5 and 5 hours after dosing. From Day 57 to Day 183, a single sample was collected.
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Plasma concentration of Bimekizumab (BKZ) over time - at Day 183 | ||||||||
End point description |
BKZ plasma concentration was expressed as geometric mean concentration and measure in nanograms per milillitre (ng/mL).
Note 1: Values Bellow Limit of Quantification (BLQ) are replaced by value of Lower Limit Of Quantification (LLOQ)/2 (=75ng/mL) in calculations of descriptive statistics.
Note 2: Descriptive statistics were only calculated if at least 2/3 of the concentrations were quantified at the respective timepoint.
Note 3: As more than 1/3 of data was BLQ, or missing, Geometric Mean could not be calculated and a placeholder value '999' was used instead, for technical reasons.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Day 1 sampling for PK evaluation was done: predose (1h prior dosing), 1h (post infusion), and 5h (±1h). At Day 22, 43 blood sampling was done prior dosing, at 1.5 and 5 hours after dosing. From Day 57 to Day 183, a single sample was collected.
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
From Baseline, at Day 1 and up to Early Withdrawal Visit, post Week 26
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.0
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
BKZ 560/420 mg (SS)
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects were administered 560 mg of bimekizumab (BKZ) iv infusion at Visit 2 (Day 1) and 2 doses of 420 mg sc BKZ injections at Visit 3 (Day 22 ± 2 days) and Visit 4 (Day 43 ± 2 days), forming the SS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo (SS)
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects were administered one dose of intravenous (iv) placebo infusion at Visit 2 (Day 1) and 2 doses of subcutaneous placebo (sc) injections at Visit 3 (Day 22 ± 2 days) and Visit 4 (Day 43 ± 2 days), forming the Safety Set (SS). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
03 Jul 2017 |
Adjusted the timing for the Screening Visits, revised the washout duration for concomitant medications, and introduced wording for a potential interim analysis and a new stopping rule should the interim analysis be carried out. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| Early study termination, due to an imbalance of adverse events with no clear evidence of benefits, resulted in a number of subjects that was too small to enable any definitive conclusions. | |||
