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

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to evaluate the pharmacokinetics and safety 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

Conditions
-----------------
Rheumatoid Arthritis

Intervention / Treatment
-----------------
* Drug: Certolizumab pegol


Participation Criteria
=================
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: Not a woman of childbearing potential (WOCBP) OR 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: >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) white blood cell count <3.00x103/μL absolute neutrophil count (ANC) <1.5x103/μL lymphocyte count <500 cells/μL hemoglobin <8.5 g/dL 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 69 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Certolizumab pegol<br>Subjects in this arm will receive doses of certolizumab pegol for the treatment of Rheumatoid Arthritis, in accordance with the US label. | Drug: Certolizumab pegol<br>* Pharmaceutical form: Solution for injection Route of administration: Subcutaneous Subjects will receive certolizumab pegol in a pre-specified sequence during the study.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Rheumatoid arthritis, Phase 1, Cimzia, Certolizumab pegol, Electrochemiluminescent immune-assay