A Study to Assess the Pharmacokinetics of Certolizumab Pegol in Adults With Active Rheumatoid Arthritis

• ClinicalTrials.gov Identifier: NCT04740814
• Recruitment Status: Completed
• First Posted: February 5, 2021
• Results First Posted: November 13, 2023
• Last Update Posted: February 12, 2024
• Sponsor: UCB Biopharma SRL
• Information provided by (Responsible Party): UCB Pharma ( UCB Biopharma SRL )

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Basic Science
• Condition: Rheumatoid Arthritis
• Intervention: Drug: Certolizumab pegol
• Enrollment: 33

Participant Flow

Recruitment Details	The study started to enroll participants in February 2021 and concluded in June 2022.
Pre-assignment Details	The Participant Flow refers to the Safety Set.

Arm/Group Title	Certolizumab Pegol (All Participants)
Arm/Group Description	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.
Period Title: Overall Study
Started	33
Completed	23
Not Completed	10
Reason Not Completed
Adverse Event	3
Protocol Violation	2
Lost to Follow-up	2
Withdrawal by Subject	3

Baseline Characteristics

Arm/Group Title		Certolizumab Pegol (All Participants)
Arm/Group Description		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.
Overall Number of Baseline Participants		33
Baseline Analysis Population Description		Baseline Characteristics refer to the Safety Set (SS) which consisted of all study participants enrolled who received greater than or equal to (≥) 1 injection of study medication.
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	33 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	27 81.8%
	>=65 years	6 18.2%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	33 participants
		55.9 (10.6)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	33 participants
	Female	22 66.7%
	Male	11 33.3%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	33 participants
	Black	7 21.2%
	White	25 75.8%
	Missing	1 3.0%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	33 participants
	Hispanic or Latino	9 27.3%
	Not Hispanic or Latino	24 72.7%

Outcome Measures

1. Primary Outcome

Title	Minimum Observed Plasma Concentration (Cmin) Post 10 Weeks of Certolizumab Pegol Dosing
Description	Cmin is the Minimum observed plasma drug concentration during a dosage interval.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Certolizumab Pegol (All Participants)
Arm/Group Description:	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.
Overall Number of Participants Analyzed	25
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: micrograms per milliliter (ug/mL)
	24.93; (44.9%)

2. Primary Outcome

Title	Area Under the Concentration-time Curve Over One Dosing Interval (AUC0-tau) of Certolizumab Pegol
Description	AUCtau is the area Under the plasma concentration-time curve from time zero to tau for the dosing interval following administration at Week 10.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Certolizumab Pegol (All Participants)
Arm/Group Description:	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.
Overall Number of Participants Analyzed	24
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: hours*ug/mL
	11890; (39.6%)

3. Secondary Outcome

Title	Plasma Concentration of Certolizumab Pegol (CZP) During the Study
Description	Plasma samples were taken at Predose and during the study at different pre and post dose time points for all participants.
Time Frame	Predose (Day 0), Day 7, 14, 42, 70, 72, 75, 77, 80, 84, 126, and 168

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title		Certolizumab Pegol (All Participants)
Arm/Group Description:		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.
Overall Number of Participants Analyzed		28
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ug/mL
Predose (Day 0)	Number Analyzed	28 participants
		NA [1]; (NA%)
Day 7	Number Analyzed	27 participants
		38.7959; (31.2%)
Day 14	Number Analyzed	27 participants
		28.7381; (25.1%)
Day 42	Number Analyzed	26 participants
		49.7912; (42.6%)
Day 70	Number Analyzed	25 participants
		29.6138; (53.6%)
Day 72	Number Analyzed	25 participants
		35.8456; (53.0%)
Day 75	Number Analyzed	25 participants
		38.8787; (42.2%)
Day 77	Number Analyzed	23 participants
		37.4564; (38.1%)
Day 80	Number Analyzed	23 participants
		33.9728; (39.1%)
Day 84	Number Analyzed	24 participants
		27.9509; (45.9%)
Day 126	Number Analyzed	24 participants
		21.2735; (129.1%)
Day 168	Number Analyzed	22 participants
		22.9050; (46.6%)

[1]

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.

4. Secondary Outcome

Title	Percentage of Participants With Treatment-emergent Serious Adverse Event (SAEs)
Description	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.
Time Frame	From Baseline to the Safety Follow-up Visit (up to Week 34)

Outcome Measure Data

Analysis Population Description

The SS included all study participants enrolled who received ≥1 injection of study medication.

Arm/Group Title	Certolizumab Pegol (All Participants)
Arm/Group Description:	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.
Overall Number of Participants Analyzed	33
Measure Type: Number; Unit of Measure: percentage of participants
	6.1

5. Secondary Outcome

Title	Percentage of Participants With Treatment-emergent Adverse Event (TEAEs) Leading to Withdrawal
Description	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.
Time Frame	From Baseline to the Safety Follow-up Visit (up to Week 34)

Outcome Measure Data

Analysis Population Description

The SS included all study participants enrolled who received ≥1 injection of study medication.

Arm/Group Title	Certolizumab Pegol (All Participants)
Arm/Group Description:	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.
Overall Number of Participants Analyzed	33
Measure Type: Number; Unit of Measure: percentage of participants
	9.1

Adverse Events

Time Frame	From Screening to the Safety Follow-up Visit (up to 38 Weeks)
Adverse Event Reporting Description	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.
Arm/Group Title	Certolizumab Pegol (All Participants)
Arm/Group Description	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.
All-Cause Mortality
	Certolizumab Pegol (All Participants)
	Affected / at Risk (%)
Total	1/33 (3.03%)
Serious Adverse Events
	Certolizumab Pegol (All Participants)
	Affected / at Risk (%)	# Events
Total	2/33 (6.06%)
Cardiac disorders
Cardiac arrest * 1	1/33 (3.03%)	1
Nervous system disorders
Cerebrovascular accident * 1	1/33 (3.03%)	1
1 Term from vocabulary, MedDRA version 23.1; * Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Certolizumab Pegol (All Participants)
	Affected / at Risk (%)	# Events
Total	9/33 (27.27%)
Gastrointestinal disorders
Nausea * 1	2/33 (6.06%)	2
Infections and infestations
Upper respiratory tract infection * 1	3/33 (9.09%)	3
Urinary tract infection * 1	2/33 (6.06%)	2
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis * 1	2/33 (6.06%)	2
1 Term from vocabulary, MedDRA version 23.1; * Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: UCB
• Organization: Cares
• Phone: 001 844 599 2273
• EMail: UCBCares@ucb.com

• Responsible Party: UCB Pharma ( UCB Biopharma SRL )
• ClinicalTrials.gov Identifier: NCT04740814
• Other Study ID Numbers: RA0138
• First Submitted: February 2, 2021
• First Posted: February 5, 2021
• Results First Submitted: January 24, 2023
• Results First Posted: November 13, 2023
• Last Update Posted: February 12, 2024