Trial Outcomes & Findings for A Study to Assess the Pharmacokinetics of Certolizumab Pegol in Adults With Active Rheumatoid Arthritis (NCT NCT04740814)
NCT ID: NCT04740814
Last Updated: 2024-02-12
Results Overview
Cmin is the Minimum observed plasma drug concentration during a dosage interval.
COMPLETED
PHASE1
33 participants
Plasma samples were collected at Pre dose on Day 70 (Week 10), 72, 75, 77 and 80 post-Week 10 study Investigational Medicinal Product (IMP) administration, and Pre dose on Day 84 (Week 12)
2024-02-12
Participant Flow
The study started to enroll participants in February 2021 and concluded in June 2022.
The Participant Flow refers to the Safety Set.
Participant milestones
| Measure |
Certolizumab Pegol (All Participants)
Participants received subcutaneous (sc) injections of certolizumab pegol (CZP) 400 milligram (mg) as loading dose at Weeks 0, 2, and 4, followed by CZP 200 mg as maintenance dose, every 2 Weeks (Q2W), up to Week 24 of the Treatment Period.
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|---|---|
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Overall Study
STARTED
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33
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Overall Study
COMPLETED
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23
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Overall Study
NOT COMPLETED
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10
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Reasons for withdrawal
| Measure |
Certolizumab Pegol (All Participants)
Participants received subcutaneous (sc) injections of certolizumab pegol (CZP) 400 milligram (mg) as loading dose at Weeks 0, 2, and 4, followed by CZP 200 mg as maintenance dose, every 2 Weeks (Q2W), up to Week 24 of the Treatment Period.
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Overall Study
Adverse Event
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3
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Overall Study
Protocol Violation
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2
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Overall Study
Lost to Follow-up
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2
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Overall Study
Withdrawal by Subject
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3
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Baseline Characteristics
A Study to Assess the Pharmacokinetics of Certolizumab Pegol in Adults With Active Rheumatoid Arthritis
Baseline characteristics by cohort
| Measure |
Certolizumab Pegol (All Participants)
n=33 Participants
Participants received subcutaneous (sc) injections of certolizumab pegol (CZP) 400 milligram (mg) as loading dose at Weeks 0, 2, and 4, followed by CZP 200 mg as maintenance dose, every 2 Weeks (Q2W), up to Week 24 of the Treatment Period.
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Age, Categorical
<=18 years
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0 Participants
n=5 Participants
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Age, Categorical
Between 18 and 65 years
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27 Participants
n=5 Participants
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Age, Categorical
>=65 years
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6 Participants
n=5 Participants
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Age, Continuous
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55.9 years
STANDARD_DEVIATION 10.6 • n=5 Participants
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Sex: Female, Male
Female
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22 Participants
n=5 Participants
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Sex: Female, Male
Male
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11 Participants
n=5 Participants
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Race/Ethnicity, Customized
Black
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7 Participants
n=5 Participants
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Race/Ethnicity, Customized
White
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25 Participants
n=5 Participants
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Race/Ethnicity, Customized
Missing
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1 Participants
n=5 Participants
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Race/Ethnicity, Customized
Hispanic or Latino
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9 Participants
n=5 Participants
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Race/Ethnicity, Customized
Not Hispanic or Latino
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24 Participants
n=5 Participants
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PRIMARY outcome
Timeframe: Plasma samples were collected at Pre dose on Day 70 (Week 10), 72, 75, 77 and 80 post-Week 10 study Investigational Medicinal Product (IMP) administration, and Pre dose on Day 84 (Week 12)Population: The Pharmacokinetic Set (PKS) included the study participants who had provided plasma samples with measurable concentrations (with recorded sampling time) on at least 1 visit, and who had no important protocol deviations affecting the PK parameters. Here, Number of participants analyzed included those participants who were evaluable for the assessment.
Cmin is the Minimum observed plasma drug concentration during a dosage interval.
Outcome measures
| Measure |
Certolizumab Pegol (All Participants)
n=25 Participants
Participants received subcutaneous (sc) injections of certolizumab pegol (CZP) 400 milligram (mg) as loading dose at Weeks 0, 2, and 4, followed by CZP 200 mg as maintenance dose, every 2 Weeks (Q2W), up to Week 24 of the Treatment Period.
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|---|---|
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Minimum Observed Plasma Concentration (Cmin) Post 10 Weeks of Certolizumab Pegol Dosing
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24.93 micrograms per milliliter (ug/mL)
Geometric Coefficient of Variation 44.9
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PRIMARY outcome
Timeframe: Plasma samples were collected at Pre dose on Day 70 (Week 10), 72, 75, 77 and 80 post-Week 10 study IMP administration, and Pre dose on Day 84 (Week 12)Population: The PKS included the study participants who had provided plasma samples with measurable concentrations (with recorded sampling time) on at least 1 visit, and who had no important protocol deviations affecting the PK parameters. Here, Number of participants analyzed included those participants who were evaluable for the assessment.
AUCtau is the area Under the plasma concentration-time curve from time zero to tau for the dosing interval following administration at Week 10.
Outcome measures
| Measure |
Certolizumab Pegol (All Participants)
n=24 Participants
Participants received subcutaneous (sc) injections of certolizumab pegol (CZP) 400 milligram (mg) as loading dose at Weeks 0, 2, and 4, followed by CZP 200 mg as maintenance dose, every 2 Weeks (Q2W), up to Week 24 of the Treatment Period.
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|---|---|
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Area Under the Concentration-time Curve Over One Dosing Interval (AUC0-tau) of Certolizumab Pegol
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11890 hours*ug/mL
Geometric Coefficient of Variation 39.6
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SECONDARY outcome
Timeframe: Predose (Day 0), Day 7, 14, 42, 70, 72, 75, 77, 80, 84, 126, and 168Population: The PKS included the study participants who had provided plasma samples with measurable concentrations (with recorded sampling time) on at least 1 visit, and who had no important protocol deviations affecting the PK parameters. Here, Number of participants analyzed included those participants who were evaluable for the assessment and 'n' (Number analyzed) signifies participants who were evaluable at specified time points.
Plasma samples were taken at Predose and during the study at different pre and post dose time points for all participants.
Outcome measures
| Measure |
Certolizumab Pegol (All Participants)
n=28 Participants
Participants received subcutaneous (sc) injections of certolizumab pegol (CZP) 400 milligram (mg) as loading dose at Weeks 0, 2, and 4, followed by CZP 200 mg as maintenance dose, every 2 Weeks (Q2W), up to Week 24 of the Treatment Period.
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|---|---|
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Plasma Concentration of Certolizumab Pegol (CZP) During the Study
Day 80
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33.9728 ug/mL
Geometric Coefficient of Variation 39.1
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Plasma Concentration of Certolizumab Pegol (CZP) During the Study
Day 84
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27.9509 ug/mL
Geometric Coefficient of Variation 45.9
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Plasma Concentration of Certolizumab Pegol (CZP) During the Study
Predose (Day 0)
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NA ug/mL
Geometric Coefficient of Variation NA
As pre-specified in the Statistical Analysis Plan, values Below Limit of Quantification (BLQ) were replaced by value of Lower Limit of Quantification (LLOQ) divided by 2 (=0.016 ug/mL) in calculations of Means and Coefficient of Variations (CVs). Means and CVs were only calculated if at least 2/3 of the concentrations were quantified at the respective timepoint and if n is greater than equal to 4.
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Plasma Concentration of Certolizumab Pegol (CZP) During the Study
Day 7
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38.7959 ug/mL
Geometric Coefficient of Variation 31.2
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Plasma Concentration of Certolizumab Pegol (CZP) During the Study
Day 14
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28.7381 ug/mL
Geometric Coefficient of Variation 25.1
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Plasma Concentration of Certolizumab Pegol (CZP) During the Study
Day 42
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49.7912 ug/mL
Geometric Coefficient of Variation 42.6
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Plasma Concentration of Certolizumab Pegol (CZP) During the Study
Day 70
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29.6138 ug/mL
Geometric Coefficient of Variation 53.6
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Plasma Concentration of Certolizumab Pegol (CZP) During the Study
Day 72
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35.8456 ug/mL
Geometric Coefficient of Variation 53.0
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Plasma Concentration of Certolizumab Pegol (CZP) During the Study
Day 75
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38.8787 ug/mL
Geometric Coefficient of Variation 42.2
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Plasma Concentration of Certolizumab Pegol (CZP) During the Study
Day 77
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37.4564 ug/mL
Geometric Coefficient of Variation 38.1
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Plasma Concentration of Certolizumab Pegol (CZP) During the Study
Day 126
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21.2735 ug/mL
Geometric Coefficient of Variation 129.1
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Plasma Concentration of Certolizumab Pegol (CZP) During the Study
Day 168
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22.9050 ug/mL
Geometric Coefficient of Variation 46.6
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SECONDARY outcome
Timeframe: From Baseline to the Safety Follow-up Visit (up to Week 34)Population: The SS included all study participants enrolled who received ≥1 injection of study medication.
A treatment-emergent adverse event (TEAE) was defined as events that have a start date on or following the first administration of study treatment in this study through the final administration of study treatment+70 days through Safety Follow-up (SFU) visit. A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: Results in death, Is life-threatening, Requires in patient hospitalization or prolongation of existing hospitalization, Results in persistent disability/incapacity, Is a congenital anomaly or birth defect, Other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above.
Outcome measures
| Measure |
Certolizumab Pegol (All Participants)
n=33 Participants
Participants received subcutaneous (sc) injections of certolizumab pegol (CZP) 400 milligram (mg) as loading dose at Weeks 0, 2, and 4, followed by CZP 200 mg as maintenance dose, every 2 Weeks (Q2W), up to Week 24 of the Treatment Period.
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Percentage of Participants With Treatment-emergent Serious Adverse Event (SAEs)
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6.1 percentage of participants
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SECONDARY outcome
Timeframe: From Baseline to the Safety Follow-up Visit (up to Week 34)Population: The SS included all study participants enrolled who received ≥1 injection of study medication.
An Adverse event (AE) was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study medication. A TEAE was defined as events that have a start date on or following the first administration of study treatment in this study through the final administration of study treatment+70 days through Safety Follow-up (SFU) visit.
Outcome measures
| Measure |
Certolizumab Pegol (All Participants)
n=33 Participants
Participants received subcutaneous (sc) injections of certolizumab pegol (CZP) 400 milligram (mg) as loading dose at Weeks 0, 2, and 4, followed by CZP 200 mg as maintenance dose, every 2 Weeks (Q2W), up to Week 24 of the Treatment Period.
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|---|---|
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Percentage of Participants With Treatment-emergent Adverse Event (TEAEs) Leading to Withdrawal
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9.1 percentage of participants
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Adverse Events
Certolizumab Pegol (All Participants)
Serious adverse events
| Measure |
Certolizumab Pegol (All Participants)
n=33 participants at risk
Participants received subcutaneous (sc) injections of certolizumab pegol (CZP) 400 milligram (mg) as loading dose at Weeks 0, 2, and 4, followed by CZP 200 mg as maintenance dose, every 2 Weeks (Q2W), up to Week 24 of the Treatment Period.
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|---|---|
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Cardiac disorders
Cardiac arrest
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3.0%
1/33 • Number of events 1 • From Screening to the Safety Follow-up Visit (up to 38 Weeks)
An AE was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication. The SS included all study participants enrolled who received ≥1 injection of study medication. All AEs from Screening until the End of study are reported here.
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Nervous system disorders
Cerebrovascular accident
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3.0%
1/33 • Number of events 1 • From Screening to the Safety Follow-up Visit (up to 38 Weeks)
An AE was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication. The SS included all study participants enrolled who received ≥1 injection of study medication. All AEs from Screening until the End of study are reported here.
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Other adverse events
| Measure |
Certolizumab Pegol (All Participants)
n=33 participants at risk
Participants received subcutaneous (sc) injections of certolizumab pegol (CZP) 400 milligram (mg) as loading dose at Weeks 0, 2, and 4, followed by CZP 200 mg as maintenance dose, every 2 Weeks (Q2W), up to Week 24 of the Treatment Period.
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|---|---|
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Gastrointestinal disorders
Nausea
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6.1%
2/33 • Number of events 2 • From Screening to the Safety Follow-up Visit (up to 38 Weeks)
An AE was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication. The SS included all study participants enrolled who received ≥1 injection of study medication. All AEs from Screening until the End of study are reported here.
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Infections and infestations
Upper respiratory tract infection
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9.1%
3/33 • Number of events 3 • From Screening to the Safety Follow-up Visit (up to 38 Weeks)
An AE was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication. The SS included all study participants enrolled who received ≥1 injection of study medication. All AEs from Screening until the End of study are reported here.
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Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
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6.1%
2/33 • Number of events 2 • From Screening to the Safety Follow-up Visit (up to 38 Weeks)
An AE was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication. The SS included all study participants enrolled who received ≥1 injection of study medication. All AEs from Screening until the End of study are reported here.
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Infections and infestations
Urinary tract infection
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6.1%
2/33 • Number of events 2 • From Screening to the Safety Follow-up Visit (up to 38 Weeks)
An AE was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication. The SS included all study participants enrolled who received ≥1 injection of study medication. All AEs from Screening until the End of study are reported here.
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60