A Study of Certolizumab Pegol as Additional Therapy in Chinese Patients With Active Rheumatoid Arthritis (RAPID-C)

• ClinicalTrials.gov Identifier: NCT02151851
• Recruitment Status: Completed
• First Posted: May 30, 2014
• Results First Posted: March 20, 2018
• Last Update Posted: June 28, 2018
• Sponsor: UCB Pharma SA, Belgium
• Collaborator: Parexel
• Information provided by (Responsible Party): UCB Pharma ( UCB Pharma SA, Belgium )

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Rheumatoid Arthritis
• Interventions: Biological: Certolizumab Pegol; Drug: Methotrexate; Other: Placebo
• Enrollment: 430

Participant Flow

Recruitment Details	The study started to enroll patients in July 2014 and concluded in June 2016.
Pre-assignment Details	Participant Flow refers to the Randomized Set.

Arm/Group Title	Placebo + Methotrexate	Certolizumab Pegol + Methotrexate
Arm/Group Description	Subjects will receive Placebo (1mL / prefilled syringe [PFS], ie, 2 injections) at Baseline, and Weeks 2 and 4; then Placebo (1 injection) Q2W until Week 22. All subjects will continue their treatment on Methotrexate (MTX), with or without folic acid, at the same dose and route of administration as at entry (unless there is a need to reduce the dose for reasons of toxicity, minimum dose permitted 10 mg per week).	Subjects will receive loading doses of CZP 400 mg (200 mg / prefilled syringe [PFS], ie, 2 injections) at Baseline, and Weeks 2 and 4; then CZP 200 mg (1 injection) Q2W until Week 22. All subjects will continue their treatment on Methotrexate (MTX), with or without folic acid, at the same dose and route of administration as at entry (unless there is a need to reduce the dose for reasons of toxicity, minimum dose permitted 10 mg per week).
Period Title: Overall Study
Started	114	316
Included in the Safety Set	113	316
Completed	38	186
Not Completed	76	130
Reason Not Completed
Lack of Efficacy	67	94
Protocol Violation	0	1
Withdrawal by Subject	2	5
Medical impairment	1	0
Low compliance to study visits	0	1
Subject entered into study in error	0	1
Adverse Event	6	28

Baseline Characteristics

Arm/Group Title		Placebo + Methotrexate	Certolizumab Pegol + Methotrexate	Total Title
Arm/Group Description		Subjects will receive Placebo (1mL / prefilled syringe [PFS], ie, 2 injections) at Baseline, and Weeks 2 and 4; then Placebo (1 injection) Q2W until Week 22. All subjects will continue their treatment on Methotrexate (MTX), with or without folic acid, at the same dose and route of administration as at entry (unless there is a need to reduce the dose for reasons of toxicity, minimum dose permitted 10 mg per week).	Subjects will receive loading doses of CZP 400 mg (200 mg / prefilled syringe [PFS], ie, 2 injections) at Baseline, and Weeks 2 and 4; then CZP 200 mg (1 injection) Q2W until Week 22. All subjects will continue their treatment on Methotrexate (MTX), with or without folic acid, at the same dose and route of administration as at entry (unless there is a need to reduce the dose for reasons of toxicity, minimum dose permitted 10 mg per week).	[Not Specified]
Overall Number of Baseline Participants		113	316	429
Baseline Analysis Population Description		Baseline Characteristics refer to the Safety Set which consisted of all subjects who received at least 1 dose of study medication.
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	113 participants	316 participants	429 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	107 94.7%	298 94.3%	405 94.4%
	>=65 years	6 5.3%	18 5.7%	24 5.6%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	113 participants	316 participants	429 participants
		47.1 (11.1)	48.2 (11.8)	47.9 (11.6)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	113 participants	316 participants	429 participants
	Female	95 84.1%	268 84.8%	363 84.6%
	Male	18 15.9%	48 15.2%	66 15.4%

Outcome Measures

1. Primary Outcome

Title	Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Week 24
Description	The assessments are based on a 20 % or greater improvement from Baseline to Week 24 in the number of tender joints, in the number of swollen joints, and a 20 % or greater improvement in at least 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP).
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all randomized subjects who received at least 1 dose of study medication administration and provided any efficacy data after the first administration.

NRI = non-responder imputation.

Arm/Group Title	Placebo + Methotrexate (FAS)	Certolizumab Pegol + Methotrexate (FAS)
Arm/Group Description:	Subjects will receive Placebo (1mL / prefilled syringe [PFS], ie, 2 injections) at Baseline, and Weeks 2 and 4; then Placebo (1 injection) Q2W until Week 22. All subjects will continue their treatment on Methotrexate (MTX), with or without folic acid, at the same dose and route of administration as at entry (unless there is a need to reduce the dose for reasons of toxicity, minimum dose permitted 10 mg per week).	Subjects will receive loading doses of CZP 400 mg (200 mg / prefilled syringe [PFS], ie, 2 injections) at Baseline, and Weeks 2 and 4; then CZP 200 mg (1 injection) Q2W until Week 22. All subjects will continue their treatment on Methotrexate (MTX), with or without folic acid, at the same dose and route of administration as at entry (unless there is a need to reduce the dose for reasons of toxicity, minimum dose permitted 10 mg per week).
Overall Number of Participants Analyzed	113	312
Measure Type: Number; Unit of Measure: percentage of participants
	23.9	54.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + Methotrexate (FAS), Certolizumab Pegol + Methotrexate (FAS)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	Difference of CZP + MTX versus Placebo + MTX (and corresponding p-value) was estimated from a logistic regression model with factors for treatment and region.
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.899
	Confidence Interval	(2-Sided) 95%; 2.382 to 6.382
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Week 24
Description	The assessments are based on a 50 % or greater improvement from Baseline to Week 24 in the number of tender joints, in the number of swollen joints, and a 50 % or greater improvement in at least 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP).
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all randomized subjects who received at least 1 dose of study medication administration and provided any efficacy data after the first administration.

NRI = non-responder imputation.

Arm/Group Title	Placebo + Methotrexate (FAS)	Certolizumab Pegol + Methotrexate (FAS)
Arm/Group Description:	Subjects will receive Placebo (1mL / prefilled syringe [PFS], ie, 2 injections) at Baseline, and Weeks 2 and 4; then Placebo (1 injection) Q2W until Week 22. All subjects will continue their treatment on Methotrexate (MTX), with or without folic acid, at the same dose and route of administration as at entry (unless there is a need to reduce the dose for reasons of toxicity, minimum dose permitted 10 mg per week).	Subjects will receive loading doses of CZP 400 mg (200 mg / prefilled syringe [PFS], ie, 2 injections) at Baseline, and Weeks 2 and 4; then CZP 200 mg (1 injection) Q2W until Week 22. All subjects will continue their treatment on Methotrexate (MTX), with or without folic acid, at the same dose and route of administration as at entry (unless there is a need to reduce the dose for reasons of toxicity, minimum dose permitted 10 mg per week).
Overall Number of Participants Analyzed	113	312
Measure Type: Number; Unit of Measure: percentage of participants
	7.1	36.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + Methotrexate (FAS), Certolizumab Pegol + Methotrexate (FAS)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	Difference of CZP + MTX versus Placebo + MTX (and corresponding p-value) was estimated from a logistic regression model with factors for treatment and region.
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	7.641
	Confidence Interval	(2-Sided) 95%; 3.570 to 16.352
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Week 24
Description	The assessments are based on a 70 % or greater improvement from Baseline to Week 24 in the number of tender joints, in the number of swollen joints, and a 70 % or greater improvement in at least 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP).
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all randomized subjects who received at least 1 dose of study medication administration and provided any efficacy data after the first administration.

NRI = non-responder imputation.

Arm/Group Title	Placebo + Methotrexate (FAS)	Certolizumab Pegol + Methotrexate (FAS)
Arm/Group Description:	Subjects will receive Placebo (1mL / prefilled syringe [PFS], ie, 2 injections) at Baseline, and Weeks 2 and 4; then Placebo (1 injection) Q2W until Week 22. All subjects will continue their treatment on Methotrexate (MTX), with or without folic acid, at the same dose and route of administration as at entry (unless there is a need to reduce the dose for reasons of toxicity, minimum dose permitted 10 mg per week).	Subjects will receive loading doses of CZP 400 mg (200 mg / prefilled syringe [PFS], ie, 2 injections) at Baseline, and Weeks 2 and 4; then CZP 200 mg (1 injection) Q2W until Week 22. All subjects will continue their treatment on Methotrexate (MTX), with or without folic acid, at the same dose and route of administration as at entry (unless there is a need to reduce the dose for reasons of toxicity, minimum dose permitted 10 mg per week).
Overall Number of Participants Analyzed	113	312
Measure Type: Number; Unit of Measure: percentage of participants
	2.7	16.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + Methotrexate (FAS), Certolizumab Pegol + Methotrexate (FAS)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	Difference of CZP + MTX versus Placebo + MTX (and corresponding p-value) was estimated from a logistic regression model with factors for treatment and region.
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	7.248
	Confidence Interval	(2-Sided) 95%; 2.209 to 23.786
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 24
Description	The HAQ-DI assesses the degree of difficulty experienced in 8 domains of daily living activities using 20 questions. Each domain consists of 2 or 3 items. For each question, the level of difficulty is scored from 0 to 3. A total score is computed from the item scores using the scoring rules provided by the index's author. HAQ-DI scores range from 0 to 3. Lower scores indicate less disability. Negative values indicate improvement from Baseline.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all randomized subjects who received at least 1 dose of study medication administration and provided any efficacy data after the first administration.

LOCF = last observation carried forward. Only subjects with available HAQ-DI scores at week 24 were included.

Arm/Group Title	Placebo + Methotrexate (FAS)	Certolizumab Pegol + Methotrexate (FAS)
Arm/Group Description:	Subjects will receive Placebo (1mL / prefilled syringe [PFS], ie, 2 injections) at Baseline, and Weeks 2 and 4; then Placebo (1 injection) Q2W until Week 22. All subjects will continue their treatment on Methotrexate (MTX), with or without folic acid, at the same dose and route of administration as at entry (unless there is a need to reduce the dose for reasons of toxicity, minimum dose permitted 10 mg per week).	Subjects will receive loading doses of CZP 400 mg (200 mg / prefilled syringe [PFS], ie, 2 injections) at Baseline, and Weeks 2 and 4; then CZP 200 mg (1 injection) Q2W until Week 22. All subjects will continue their treatment on Methotrexate (MTX), with or without folic acid, at the same dose and route of administration as at entry (unless there is a need to reduce the dose for reasons of toxicity, minimum dose permitted 10 mg per week).
Overall Number of Participants Analyzed	110	306
Mean (Standard Deviation); Unit of Measure: units on a scale
	-0.185 (0.463)	-0.530 (0.589)

Adverse Events

Time Frame	Adverse Events (AEs) were collected from Baseline (Week 0) up to Week 25.
Adverse Event Reporting Description	Adverse Events refer to the Safety Set which consists of all subjects who received at least 1 dose of study medication.
Arm/Group Title	Placebo + Methotrexate (SS)		Certolizumab Pegol + Methotrexate (SS)
Arm/Group Description	Subjects will receive Placebo (1mL / prefilled syringe [PFS], ie, 2 injections) at Baseline, and Weeks 2 and 4; then Placebo (1 injection) Q2W until Week 22. All subjects will continue their treatment on Methotrexate (MTX), with or without folic acid, at the same dose and route of administration as at entry (unless there is a need to reduce the dose for reasons of toxicity, minimum dose permitted 10 mg per week).		Subjects will receive loading doses of CZP 400 mg (200 mg / prefilled syringe [PFS], ie, 2 injections) at Baseline, and Weeks 2 and 4; then CZP 200 mg (1 injection) Q2W until Week 22. All subjects will continue their treatment on Methotrexate (MTX), with or without folic acid, at the same dose and route of administration as at entry (unless there is a need to reduce the dose for reasons of toxicity, minimum dose permitted 10 mg per week).
All-Cause Mortality
	Placebo + Methotrexate (SS)		Certolizumab Pegol + Methotrexate (SS)
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Placebo + Methotrexate (SS)		Certolizumab Pegol + Methotrexate (SS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/113 (2.65%)		20/316 (6.33%)
Blood and lymphatic system disorders
Anaemia * 1	0/113 (0.00%)	0	1/316 (0.32%)	1
Cardiac disorders
Aortic valve incompetence * 1	0/113 (0.00%)	0	1/316 (0.32%)	1
Cardiac arrest * 1	0/113 (0.00%)	0	1/316 (0.32%)	1
Gastrointestinal disorders
Gastric ulcer * 1	0/113 (0.00%)	0	2/316 (0.63%)	2
Gastritis * 1	0/113 (0.00%)	0	1/316 (0.32%)	1
Ascites * 1	0/113 (0.00%)	0	1/316 (0.32%)	1
Hepatobiliary disorders
Cholecystitis chronic * 1	1/113 (0.88%)	1	0/316 (0.00%)	0
Cholelithiasis * 1	1/113 (0.88%)	1	0/316 (0.00%)	0
Liver injury * 1	0/113 (0.00%)	0	2/316 (0.63%)	2
Bile duct stone * 1	1/113 (0.88%)	1	0/316 (0.00%)	0
Immune system disorders
Anaphylactic shock * 1	0/113 (0.00%)	0	1/316 (0.32%)	1
Infections and infestations
Pneumonia * 1	0/113 (0.00%)	0	2/316 (0.63%)	2
Pulmonary tuberculosis * 1	0/113 (0.00%)	0	2/316 (0.63%)	2
Pericarditis tuberculous * 1	0/113 (0.00%)	0	1/316 (0.32%)	1
Tuberculous pleurisy * 1	0/113 (0.00%)	0	1/316 (0.32%)	1
Injury, poisoning and procedural complications
Multiple fractures * 1	0/113 (0.00%)	0	1/316 (0.32%)	1
Spinal compression fracture * 1	0/113 (0.00%)	0	1/316 (0.32%)	1
Investigations
Protein urine present * 1	0/113 (0.00%)	0	1/316 (0.32%)	1
Musculoskeletal and connective tissue disorders
Osteonecrosis * 1	0/113 (0.00%)	0	1/316 (0.32%)	1
Sjogren's syndrome * 1	1/113 (0.88%)	1	0/316 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung adenocarcinoma * 1	0/113 (0.00%)	0	1/316 (0.32%)	1
Nervous system disorders
Subarachnoid haemorrhage * 1	1/113 (0.88%)	1	0/316 (0.00%)	0
Renal and urinary disorders
Haematuria * 1	0/113 (0.00%)	0	1/316 (0.32%)	1
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease * 1	0/113 (0.00%)	0	1/316 (0.32%)	1
Pleural effusion * 1	0/113 (0.00%)	0	1/316 (0.32%)	1
Respiratory failure * 1	0/113 (0.00%)	0	1/316 (0.32%)	1
Pulmonary mass * 1	0/113 (0.00%)	0	2/316 (0.63%)	2
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo + Methotrexate (SS)		Certolizumab Pegol + Methotrexate (SS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	48/113 (42.48%)		130/316 (41.14%)
Blood and lymphatic system disorders
Anaemia * 1	7/113 (6.19%)	9	17/316 (5.38%)	19
Infections and infestations
Upper respiratory tract infection * 1	15/113 (13.27%)	21	50/316 (15.82%)	60
Latent tuberculosis * 1	7/113 (6.19%)	7	24/316 (7.59%)	24
Urinary tract infection * 1	7/113 (6.19%)	11	13/316 (4.11%)	18
Investigations
Liver function test abnormal * 1	4/113 (3.54%)	6	22/316 (6.96%)	24
Alanine aminotransferase increased * 1	8/113 (7.08%)	9	19/316 (6.01%)	26
White blood cell count decreased * 1	1/113 (0.88%)	1	18/316 (5.70%)	24
Aspartate aminotransferase increased * 1	7/113 (6.19%)	8	16/316 (5.06%)	18
Neutrophil count increased * 1	8/113 (7.08%)	12	6/316 (1.90%)	6
Lymphocyte count decreased * 1	8/113 (7.08%)	11	2/316 (0.63%)	2
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA

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: +1844 599 ext 2273
• EMail: UCBCares@ucb.com

• Responsible Party: UCB Pharma ( UCB Pharma SA, Belgium )
• ClinicalTrials.gov Identifier: NCT02151851
• Other Study ID Numbers: RA0044
• First Submitted: May 28, 2014
• First Posted: May 30, 2014
• Results First Submitted: June 7, 2017
• Results First Posted: March 20, 2018
• Last Update Posted: June 28, 2018