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 )

Tracking Information

• First Submitted Date: February 2, 2021
• First Posted Date: February 5, 2021
• Results First Submitted Date: January 24, 2023
• Results First Posted Date: November 13, 2023
• Last Update Posted Date: February 12, 2024
• Actual Study Start Date: February 11, 2021
• Actual Primary Completion Date: January 24, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 24, 2023)

• Minimum Observed Plasma Concentration (Cmin) Post 10 Weeks of Certolizumab Pegol Dosing [ 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) ]
  Cmin is the Minimum observed plasma drug concentration during a dosage interval.
• Area Under the Concentration-time Curve Over One Dosing Interval (AUC0-tau) of Certolizumab Pegol [ 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) ]
  AUCtau is the area Under the plasma concentration-time curve from time zero to tau for the dosing interval following administration at Week 10.

Original Primary Outcome Measures (submitted: February 2, 2021)

• Minimum observed plasma concentration (Cmin) after 10 weeks of certolizumab pegol dosing [ Time Frame: From Week 10 to Week 12 ]
  Cmin: Minimum observed plasma concentration
• Area under the concentration-time curve over one dosing interval (AUCtau) of certolizumab pegol [ Time Frame: From Week 10 to Week 12 ]
  AUCtau: Area under the concentration-time curve over one dosing interval

Current Secondary Outcome Measures (submitted: January 24, 2023)

• Plasma Concentration of Certolizumab Pegol (CZP) During the Study [ Time Frame: Predose (Day 0), Day 7, 14, 42, 70, 72, 75, 77, 80, 84, 126, and 168 ]
  Plasma samples were taken at Predose and during the study at different pre and post dose time points for all participants.
• Percentage of Participants With Treatment-emergent Serious Adverse Event (SAEs) [ Time Frame: From Baseline to the Safety Follow-up Visit (up to Week 34) ]
  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.
• Percentage of Participants With Treatment-emergent Adverse Event (TEAEs) Leading to Withdrawal [ Time Frame: From Baseline to the Safety Follow-up Visit (up to Week 34) ]
  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.

Original Secondary Outcome Measures (submitted: February 2, 2021)

• Plasma Concentration of Certolizumab Pegol (CZP) during the study [ Time Frame: Baseline and during Weeks 1, 2, 6, 10, 11, 12, 18 and 24 ]
  Plasma samples will be taken at Baseline and during the study for all subjects.
• Incidence of Treatment-Emergent Serious Adverse Event (SAEs) [ Time Frame: From Baseline to the the Safety Follow-up Visit (up to Week 34) ]
  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
• Incidence of Treatment-emergent (TEAEs) leading to withdrawal [ Time Frame: From Baseline to the the Safety Follow-up Visit (up to Week 34) ]
  An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Assess the Pharmacokinetics of Certolizumab Pegol in Adults With Active Rheumatoid Arthritis
• Official Title: A Multi-Center, Open-Label Study to Evaluate the Pharmacokinetics of Certolizumab Pegol in Adults With Active Rheumatoid Arthritis Using an Electrochemiluminescent Immuno-Assay
• Brief Summary: The purpose of the study is to evaluate the pharmacokinetics and safety of certolizumab pegol in adults with active rheumatoid arthritis.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• 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

• Pharmaceutical form: Solution for injection
• Route of administration: Subcutaneous Subjects will receive certolizumab pegol in a pre-specified sequence during the study.

Study Arms

Experimental: Certolizumab pegol

Subjects in this arm will receive doses of certolizumab pegol for the treatment of Rheumatoid Arthritis, in accordance with the US label.

Intervention: Drug: Certolizumab pegol

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 11, 2022): 33
• Original Estimated Enrollment (submitted: February 2, 2021): 30
• Actual Study Completion Date: June 27, 2022
• Actual Primary Completion Date: January 24, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Participant must be 18 to 69 years of age inclusive, at the time of signing the informed consent
• Participant must have a diagnosis of moderately-to-severely active rheumatoid arthritis (RA)
• Participant must have had an inadequate response to, or intolerance to, at least 1 disease modifying antirheumatic drug (DMARD) (nonbiologic or biologic)
• Participant has a negative interferon-gamma release assay (IGRA) at Screening
• Participant has a body mass index within the range 18.0 kg/m2 to 35.0 kg/m2 (inclusive)
• Male or female

• A female participant is eligible to participate if:

  i) she is not pregnant, ii) not breastfeeding, iii) at least one of the following conditions applies:

  1. Not a woman of childbearing potential (WOCBP) OR

  2. A WOCBP who agrees to follow the contraceptive guidance during the Treatment Period and until the Safety Follow-up (SFU) Visit

     Exclusion Criteria:

• Participant has a known hypersensitivity to any components of the study medication(including polyethylene glycol) or comparative drugs (and/or an investigational device) as stated in this protocol
• Participant has clinically significant electrocardiogram (ECG) abnormalities at Screening
• Participant has previously been exposed to certolizumab pegol (CZP)
• Participant has failed treatment with ≥1 tumor necrosis factor (TNF) α inhibitor or was a primary failure for any TNFα antagonist. A primary failure is defined as no clinical disease improvement within the first 12 weeks of treatment (study participants who demonstrated clinical response within 12 weeks of treatment and subsequently lost response after 12 weeks of treatment are eligible)
• Participant has received a live vaccination within 6 weeks prior to Screening or intends to have a live vaccination during the course of the study or within 3 months following CZP treatment in the study
• Participant has received any investigational drug or experimental procedure within 90 days prior to the first dose of IMPinvestigational medicinal product (IMP)

• Participant has a laboratory abnormality at Screening, including any of the following:

  1. >3.0x upper limit of normal (ULN) of any of the following: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP); or >ULN total bilirubin (>1.5x ULN total bilirubin if the participant has a documented pre-study diagnosis of Gilbert's syndrome)
  2. white blood cell count <3.00x103/μL
  3. absolute neutrophil count (ANC) <1.5x103/μL
  4. lymphocyte count <500 cells/μL
  5. hemoglobin <8.5 g/dL
  6. Any other laboratory abnormality, which, in the opinion of the Investigator, will prevent the study participant from completing the study or will interfere with the interpretation of the study results

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 69 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04740814
• Other Study ID Numbers: RA0138
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: Due to the small sample size in this trial, Individual Patient Data cannot be adequately anonymized and there is a reasonable likelihood that individual participants could be re-identified. For this reason, data from this trial cannot be shared.

• Current Responsible Party: UCB Pharma ( UCB Biopharma SRL )
• Original Responsible Party: Same as current
• Current Study Sponsor: UCB Biopharma SRL
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: UCB Cares; 001 844 599 2273 (UCB)

• PRS Account: UCB Pharma
• Verification Date: February 2024