Low-dose Recombinant Human IL-2 for the Treatment of Rheumatoid Arthritis

• Sponsor: Peking University People's Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT02467504
• Collaborator: Monash University (Other), Beijing ShuangLu Pharmaceutical Co., Ltd. (Other)
• Enrollment: 47
• Location: 1
• Arms: 2
• Actual Duration (Months): 26
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease, characterized by symmetric poly-arthritis usually involving the small joints of the hands and feet. In addition, various extra-joint manifestations may develop. Several immunomodulating agents have been attempted in the treatment of RA without achieving satisfactory results. Dysfunction of regulatory T (Treg) cells has been detected in diverse autoimmune diseases, which can be promoted by interleukin-2 (IL-2). The investigators hypothesized that low-dose IL-2 could be a novel therapy in active RA patients. This clinical study will test the efficacy and safety of low dose IL-2 treatment in RA. The investigators perform a single-centre, double-blind pilot trial with hrIL-2 in RA. The investigators evaluate the effectiveness and safeness of low-dose hrIL-2 for RA by randomized controlled study (hrIL-2 (N = 23) + Methotrexate (MTX)+ Loxoprofen versus placebo+MTX + Loxoprofen group (N = 24)).

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: hrIL-2 active; Drug: hrIL-2 placebo; Drug: MTX; Drug: Folic Acid; Drug: Loxoprofen	Phase 2

Detailed Description

Each RA patients (n=47) with DAS>3.2 received low-dose IL-2+MTX+ Loxoprofen or placebo+MTX + Loxoprofen (active group: placebo group =1:1, 1 million units every other day subcutaneously (hrIL-2 1×106, ip, Qod) for a period of 14 days. After a 14-day rest, another cycle started) for 3 cycles. The end points were safety and clinical and immunologic response.

Study Design

• Study Type: Interventional
• Actual Enrollment: 47 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double Blind, Placebo-controlled Pilot-study to Evaluate Efficacy and Safety of Low-dose hrIL-2 in the Treatment of Methotrexate (MTX)-Naive Patients With Rheumatoid Arthritis
• Actual Study Start Date: Jul 1, 2015
• Actual Primary Completion Date: Jan 15, 2017
• Actual Study Completion Date: Aug 31, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Experimental hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX Folic acid Loxoprofen	Drug: hrIL-2 active; hrIL-2 active (1 million U doses of hrIL-2s.c.injection); Other Names: Human recombinant IL-2 ; Drug: MTX; Methotrexate (oral administration); Drug: Folic Acid; Folic Acid (oral administration); Drug: Loxoprofen; Loxoprofen (oral administration)
Placebo Comparator: Placebo Comparator hrIL-2 placebo (1 million U doses of placebo s.c.injection) MTX Folic acid Loxoprofen	Drug: hrIL-2 placebo; hrIL-2 placebo (1 million U doses of hrIL-2 placebo s.c.injection); Other Names: placebo ; Drug: MTX; Methotrexate (oral administration); Drug: Folic Acid; Folic Acid (oral administration); Drug: Loxoprofen; Loxoprofen (oral administration)

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Achieving DAS28 Remission. [week 24]

   DAS 28 remission is defined by a disease activity score (28 joint) calculated using the erythrocyte sedimentation rate (DAS28-ESR) of less than 2.6

2. Percentage of Participants Meeting the American College of Rheumatology 20% Response Criteria [week 12, week 24]

   The assessments are based on a 20% or greater improvement from Baseline in the number of tender joints, a 20%, or more improvement in the number of swollen joints, and a 20% or greater improvement in 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).

3. The Change From Baseline of Clinical Disease Activity Index (CDAI) [week 12, week 24]

   Clinical Disease Activity Index(CDAI), the minimum is 0, the maximum is 76. higher scores mean a worse outcome. The change of from baseline of CDAI, the minimum is -76, the maximum is 76. higher scores mean a worse outcome.

4. The Change From Baseline of Simplified Disease Activity Index (SDAI) [week 12, week 24]

   Simplified Disease Activity Index(SDAI). the minimum is 0, the maximum is 96. higher scores mean worse outcome. The change from baseline of SDAI. the minimum is -96, the maximum is 96. higher scores mean worse outcome.

Secondary Outcome Measures

1. Number of Participants With Adverse Events [Up to week 24]

   adverse events includes injection site reactions, influenza-like symptoms, infection, fever, tumor, cardiovascular event, drug-induced liver and kidney damage.

2. Percentage of CD4+ Treg Cells [week 12, week 24]

   analysis regulatory CD4+ T(Treg) cells before and during IL-2 treatment. P values<0.05 are considered statistically significant.

3. Percentage of Participants Achieving DAS28 Low Disease Activity. [week 12, week 24]

   Low disease activity is defined by a disease activity score (28 joint) calculated using the erythrocyte sedimentation rate (DAS28-ESR) of less than 3.2

4. Percentage of Participants Achieving a Good or Moderate European League Against Rheumatism (EULAR) Response [week 12, week 24]

   Good response is defined as: DAS28-ESR ≤ 3.2 and decrease from Baseline by > 1.2. moderate response is defined as achievement of one of the following: DAS28-ESR ≤ 3.2 and decrease from Baseline > 0.6 and ≤ 1.2 DAS28-ESR > 3.2 and ≤ 5.1 and decrease from Baseline > 0.6 DAS28-ESR > 5.1 and decrease from Baseline >1.2.

5. Percentage of Participants Meeting the American College of Rheumatology 50% Response Criteria [week 12, week 24]

   The assessments are based on a 50% or greater improvement from Baseline in the number of tender joints, a 50%, or more improvement in the number of swollen joints, and a 50% or greater improvement in 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).

6. Percentage of Participants Meeting the American College of Rheumatology 70% Response Criteria [week 12, week 24]

   The assessments are based on a 70% or greater improvement from Baseline in the number of tender joints, a 70%, or more improvement in the number of swollen joints, and a 70% or greater improvement in 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).

7. Percentage of Participants Meeting the 2011 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) Remission Criteria Simplified for Clinical Practice [week 12, week 24]

   The 2011 ACR/EULAR remission criteria simplified for clinical practice is defined as:Tender Joint Count (TJC) ≤ 1, Swollen Joint Count (SJC) ≤ 1 and Patient's Global Assessment of Disease Activity (PtGADA) ≤ 1.

8. The Change From Baseline of a Health Assessment Questionnaire- Disability Index (HAQ-DI) [week 12, week 24]

   The domains of the HAQ-DI are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. The total score ranges from 0 to 3 with lower scores meaning lower disability. The change from baseline of HAQ-DI, minimum is -3, the maximum is 3. higher scores mean a worse outcome.

9. The Scores of SF-36 Quetionnaire [week 12, week 24]

   Score ranging from 0 to 100 with higher scores a better outcome.

10. Work Productivity Survey - Rheumatoid Arthritis [WPS-RA] [week 24]

    The Arthritis interference in the last month with work productivity is measured on a scale that ranges from 0 (no interference) to 10 (complete interference). The Arthritis interference in the last month with household work productivity is measured on a scale that ranges from 0 (no interference) to 10 (complete interference).higher scores mean a worse outcome.

11. Erythrocyte Sedimentation Rate (ESR) [week 12, week 24]

12. C Reactive Protein (CRP) [week 12, week 24]

13. The Change From Baseline of Patient's Global Assessment of Disease Activity (PtGADA) [week 12, week 24]

    VAS score from 0 to 100 for Patient's Global Assessment of Disease Activity Higher scores mean a worse outcome. The change from baseline of PtGADA, the minimum is -100, the maximum is 100. Higher scores mean a worse outcome.

14. The Change From Baseline of Physician's Global Assessment of Disease Activity (PhGADA) [week 12, week 24]

    VAS score from 0 to 100 for Physician's Global Assessment of Disease Activity higher scores mean a worse outcome. The change from baseline, the minimum is -100, the maximum is 100.

15. The Change From Baseline of Patient's Assessment of Arthritis Pain (PtAAP) [week 12, week 24]

    VAS score from 0 to 100 for Patient's Assessment of Arthritis Pain higher scores mean a worse outcome. The change from baseline of PtAAP, the minimum is -100, the maximum is 100.

16. Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]-2 [week 24]

    In the last month, number of work days missed, number of work days with reduced productivity. In the last month, number of days with no household work, number of days with reduced household work productivity, number of days with hired outside help, number of days missed of family/social/leisure activities in the last month.higher scores mean a worse outcome.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female ≥18 and ≤70 years of age at time of screening

• Diagnosed with rheumatoid arthritis

• Must have active disease with DMARDs (Disease Modifying Anti-Rheumatic Drugs) except MTX, the doses had been stable for at least 3 months before baseline

• Moderate or severe rheumatoid arthritis during screening, as defined by a disease activity score (28 joint) calculated using the C-reactive protein formula (DAS28-ESR)

3.2

• Have given written informed consent

Exclusion Criteria:

• Patient presenting or having a history of other inflammatory joint disease

• Patient with ongoing or previous Stevens-Johnson syndrome, toxic epidermal necrolysis or erythema multiforme

• Patient with significantly impaired bone marrow function or significant anaemia, leucopenia or thrombocytopenia due to causes or other than active rheumatoid arthritis

• Persistent infection or severe infection within 3 months before enrollment,

• Uncontrolled hypertension, uncontrolled diabetes, unstable ischemic heart disease, active inflammatory bowel disease, active peptic ulcer disease, terminal illness or other medical condition which, in the opinion of the investigator, would put the patient at risk to participate in the study,

• Clinically relevant cardiovascular, hepatic, neurological, endocrine, or other major systemic disease making implementation of the protocol or interpretation of the study results difficult

• Severe hypoproteinemia (e.g., in case of severe liver disease or nephrotic syndrome) with serum albumin < 30 g/L

• Moderate or severe impairment of renal function, as known by serum creatinine > 133μmol/L (or 1.5 mg/dl)

• Patient with history of recent and clinically significant drug or alcohol abuse

• Impairment of liver function or persisting ALT (SGPT) elevations of more than 2-fold the upper limit of normal

• Known HIV positive status

• Known positive serology for hepatitis B or C

• Patient with hypersensitivity to any of the excipients in the tablets of methotrexate

• Pregnancy

• Breastfeeding

• Women of childbearing potential, except if they fulfill specific conditions,

• Men wishing to father children during the course of the study or within the 24 months thereafter (or 3 month with the washout procedure)

• Patient with a congenital or acquired severe immuno-deficiency, a history of cancer or lymphoproliferative disease, or any patient who has received total lymphoid irradiation.

• Enrollment in any other clinical trial involving off-label use of an investigational drug or device, or enrollment in any other type of medical research

• Any active infection (including chronic or localized infections) for which anti-infectives were indicated within 28 days prior to first investigational product dose

• BMI(body mass index) under 18.5 kg/m2 or more than 30 kg/m2

• The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Rheumatology and Immunology, Peking University People's Hospital	Beijing	Beijing	China	100044

Sponsors and Collaborators

• Peking University People's Hospital
• Monash University
• Beijing ShuangLu Pharmaceutical Co., Ltd.

Investigators

• Principal Investigator: Zhanguo Li, MD PhD, Peking University Institute of Rheuamotology and Immunology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Zhanguo Li, Dept. Rheumatology and immunology,Peking University People's Hospital, Peking University People's Hospital
• ClinicalTrials.gov Identifier: NCT02467504
• Other Study ID Numbers: hrIL-2 RA
• First Posted: Jun 10, 2015
• Last Update Posted: Sep 9, 2019
• Last Verified: May 1, 2019

• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Folic Acid; Loxoprofen

Study Results

Participant Flow

Arm/Group Title	Experimental	Placebo Comparator
Arm/Group Description	hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX Folic acid Loxoprofen hrIL-2 active: hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)	hrIL-2 placebo (1 million U doses of placebo s.c.injection) MTX Folic acid Loxoprofen hrIL-2 placebo: hrIL-2 placebo (1 million U doses of hrIL-2 placebo s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)
Period Title: Overall Study
STARTED	23	24
COMPLETED	17	23
NOT COMPLETED	6	1

Baseline Characteristics

Arm/Group Title	Experimental	Placebo Comparator	Total
Arm/Group Description	hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX Folic acid Loxoprofen hrIL-2 active: hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)	hrIL-2 placebo (1 million U doses of placebo s.c.injection) MTX Folic acid Loxoprofen hrIL-2 placebo: hrIL-2 placebo (1 million U doses of hrIL-2 placebo s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)	Total of all reporting groups
Overall Participants	23	24	47
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.6 (10.9)	56.4 (9.9)	54.5 (10.5)
Sex/Gender, Customized (Count of Participants)
Female	20 87%	20 83.3%	40 85.1%
Male	3 13%	4 16.7%	7 14.9%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Achieving DAS28 Remission.
Description	DAS 28 remission is defined by a disease activity score (28 joint) calculated using the erythrocyte sedimentation rate (DAS28-ESR) of less than 2.6
Time Frame	week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental	Placebo Comparator
Arm/Group Description	hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX Folic acid Loxoprofen hrIL-2 active: hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)	hrIL-2 placebo (1 million U doses of placebo s.c.injection) MTX Folic acid Loxoprofen hrIL-2 placebo: hrIL-2 placebo (1 million U doses of hrIL-2 placebo s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)
Measure Participants	17	23
Count of Participants [Participants]	6 26.1%	6 25%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental, Placebo Comparator
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.530
	Comments
	Method	Chi-squared
	Comments

2. Primary Outcome

Title	Percentage of Participants Meeting the American College of Rheumatology 20% Response Criteria
Description	The assessments are based on a 20% or greater improvement from Baseline in the number of tender joints, a 20%, or more improvement in the number of swollen joints, and a 20% or greater improvement in 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 12, week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental	Placebo Comparator
Arm/Group Description	hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX Folic acid Loxoprofen hrIL-2 active: hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)	hrIL-2 placebo (1 million U doses of placebo s.c.injection) MTX Folic acid Loxoprofen hrIL-2 placebo: hrIL-2 placebo (1 million U doses of hrIL-2 placebo s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)
Measure Participants	17	23
week 24	13 56.5%	13 54.2%
week 12	12 52.2%	10 41.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental, Placebo Comparator
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.315
	Comments
	Method	Chi-squared
	Comments

3. Primary Outcome

Title	The Change From Baseline of Clinical Disease Activity Index (CDAI)
Description	Clinical Disease Activity Index(CDAI), the minimum is 0, the maximum is 76. higher scores mean a worse outcome. The change of from baseline of CDAI, the minimum is -76, the maximum is 76. higher scores mean a worse outcome.
Time Frame	week 12, week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental	Placebo Comparator
Arm/Group Description	hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX Folic acid Loxoprofen hrIL-2 active: hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)	hrIL-2 placebo (1 million U doses of placebo s.c.injection) MTX Folic acid Loxoprofen hrIL-2 placebo: hrIL-2 placebo (1 million U doses of hrIL-2 placebo s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)
Measure Participants	17	23
week 24	-17.5	-11
week 12	-15.0	-8.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental, Placebo Comparator
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.018
	Comments
	Method	Mixed Models Analysis
	Comments

4. Primary Outcome

Title	The Change From Baseline of Simplified Disease Activity Index (SDAI)
Description	Simplified Disease Activity Index(SDAI). the minimum is 0, the maximum is 96. higher scores mean worse outcome. The change from baseline of SDAI. the minimum is -96, the maximum is 96. higher scores mean worse outcome.
Time Frame	week 12, week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental	Placebo Comparator
Arm/Group Description	hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX Folic acid Loxoprofen hrIL-2 active: hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)	hrIL-2 placebo (1 million U doses of placebo s.c.injection) MTX Folic acid Loxoprofen hrIL-2 placebo: hrIL-2 placebo (1 million U doses of hrIL-2 placebo s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)
Measure Participants	17	23
week 24	-19.0	-12.1
week 12	-16.9	-9.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental, Placebo Comparator
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.015
	Comments
	Method	Mixed Models Analysis
	Comments

5. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	adverse events includes injection site reactions, influenza-like symptoms, infection, fever, tumor, cardiovascular event, drug-induced liver and kidney damage.
Time Frame	Up to week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental	Placebo Comparator
Arm/Group Description	hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX Folic acid Loxoprofen hrIL-2 active: hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)	hrIL-2 placebo (1 million U doses of placebo s.c.injection) MTX Folic acid Loxoprofen hrIL-2 placebo: hrIL-2 placebo (1 million U doses of hrIL-2 placebo s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)
Measure Participants	23	24
Count of Participants [Participants]	11 47.8%	9 37.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental, Placebo Comparator
	Comments
	Type of Statistical Test	Other
	Comments	Chi
Statistical Test of Hypothesis	p-Value	0.474
	Comments
	Method	Chi-squared
	Comments

6. Secondary Outcome

Title	Percentage of CD4+ Treg Cells
Description	analysis regulatory CD4+ T(Treg) cells before and during IL-2 treatment. P values<0.05 are considered statistically significant.
Time Frame	week 12, week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental	Placebo Comparator
Arm/Group Description	hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX Folic acid Loxoprofen hrIL-2 active: hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)	hrIL-2 placebo (1 million U doses of placebo s.c.injection) MTX Folic acid Loxoprofen hrIL-2 placebo: hrIL-2 placebo (1 million U doses of hrIL-2 placebo s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)
Measure Participants	17	23
Week 24	6.94	6.46
Week 12	6.84	5.37

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental, Placebo Comparator
	Comments
	Type of Statistical Test	Other
	Comments	description of Treg cells in CD4+ T cells
Statistical Test of Hypothesis	p-Value	0.665
	Comments
	Method	Mixed Models Analysis
	Comments

7. Secondary Outcome

Title	Percentage of Participants Achieving DAS28 Low Disease Activity.
Description	Low disease activity is defined by a disease activity score (28 joint) calculated using the erythrocyte sedimentation rate (DAS28-ESR) of less than 3.2
Time Frame	week 12, week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental	Placebo Comparator
Arm/Group Description	hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX Folic acid Loxoprofen hrIL-2 active: hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)	hrIL-2 placebo (1 million U doses of placebo s.c.injection) MTX Folic acid Loxoprofen hrIL-2 placebo: hrIL-2 placebo (1 million U doses of hrIL-2 placebo s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)
Measure Participants	17	23
week 24	8 34.8%	9 37.5%
week 12	7 30.4%	7 29.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental, Placebo Comparator
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.616
	Comments
	Method	Chi-squared
	Comments

8. Secondary Outcome

Title	Percentage of Participants Achieving a Good or Moderate European League Against Rheumatism (EULAR) Response
Description	Good response is defined as: DAS28-ESR ≤ 3.2 and decrease from Baseline by > 1.2. moderate response is defined as achievement of one of the following: DAS28-ESR ≤ 3.2 and decrease from Baseline > 0.6 and ≤ 1.2 DAS28-ESR > 3.2 and ≤ 5.1 and decrease from Baseline > 0.6 DAS28-ESR > 5.1 and decrease from Baseline >1.2.
Time Frame	week 12, week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental	Placebo Comparator
Arm/Group Description	hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX Folic acid Loxoprofen hrIL-2 active: hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)	hrIL-2 placebo (1 million U doses of placebo s.c.injection) MTX Folic acid Loxoprofen hrIL-2 placebo: hrIL-2 placebo (1 million U doses of hrIL-2 placebo s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)
Measure Participants	17	23
week 24	17 73.9%	20 83.3%
week 12	15 65.2%	14 58.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental, Placebo Comparator
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.616
	Comments
	Method	Chi-squared
	Comments

9. Secondary Outcome

Title	Percentage of Participants Meeting the American College of Rheumatology 50% Response Criteria
Description	The assessments are based on a 50% or greater improvement from Baseline in the number of tender joints, a 50%, or more improvement in the number of swollen joints, and a 50% or greater improvement in 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 12, week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental	Placebo Comparator
Arm/Group Description	hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX Folic acid Loxoprofen hrIL-2 active: hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)	hrIL-2 placebo (1 million U doses of placebo s.c.injection) MTX Folic acid Loxoprofen hrIL-2 placebo: hrIL-2 placebo (1 million U doses of hrIL-2 placebo s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)
Measure Participants	17	23
week 24	10 43.5%	8 33.3%
weed 12	6 26.1%	3 12.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental, Placebo Comparator
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.200
	Comments
	Method	Chi-squared
	Comments

10. Secondary Outcome

Title	Percentage of Participants Meeting the American College of Rheumatology 70% Response Criteria
Description	The assessments are based on a 70% or greater improvement from Baseline in the number of tender joints, a 70%, or more improvement in the number of swollen joints, and a 70% or greater improvement in 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 12, week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental	Placebo Comparator
Arm/Group Description	hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX Folic acid Loxoprofen hrIL-2 active: hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)	hrIL-2 placebo (1 million U doses of placebo s.c.injection) MTX Folic acid Loxoprofen hrIL-2 placebo: hrIL-2 placebo (1 million U doses of hrIL-2 placebo s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)
Measure Participants	17	23
week 24	4 17.4%	2 8.3%
week 12	2 8.7%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental, Placebo Comparator
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.373
	Comments
	Method	Chi-squared
	Comments

11. Secondary Outcome

Title	Percentage of Participants Meeting the 2011 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) Remission Criteria Simplified for Clinical Practice
Description	The 2011 ACR/EULAR remission criteria simplified for clinical practice is defined as:Tender Joint Count (TJC) ≤ 1, Swollen Joint Count (SJC) ≤ 1 and Patient's Global Assessment of Disease Activity (PtGADA) ≤ 1.
Time Frame	week 12, week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental	Placebo Comparator
Arm/Group Description	hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX Folic acid Loxoprofen hrIL-2 active: hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)	hrIL-2 placebo (1 million U doses of placebo s.c.injection) MTX Folic acid Loxoprofen hrIL-2 placebo: hrIL-2 placebo (1 million U doses of hrIL-2 placebo s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)
Measure Participants	17	23
week 24	2 8.7%	1 4.2%
week 12	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental, Placebo Comparator
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.565
	Comments
	Method	Chi-squared
	Comments

12. Secondary Outcome

Title	The Change From Baseline of a Health Assessment Questionnaire- Disability Index (HAQ-DI)
Description	The domains of the HAQ-DI are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. The total score ranges from 0 to 3 with lower scores meaning lower disability. The change from baseline of HAQ-DI, minimum is -3, the maximum is 3. higher scores mean a worse outcome.
Time Frame	week 12, week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental	Placebo Comparator
Arm/Group Description	hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX Folic acid Loxoprofen hrIL-2 active: hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)	hrIL-2 placebo (1 million U doses of placebo s.c.injection) MTX Folic acid Loxoprofen hrIL-2 placebo: hrIL-2 placebo (1 million U doses of hrIL-2 placebo s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)
Measure Participants	17	23
week 24	-0.63	-0.38
week 12	-0.50	-0.25

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental, Placebo Comparator
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.221
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

13. Secondary Outcome

Title	The Scores of SF-36 Quetionnaire
Description	Score ranging from 0 to 100 with higher scores a better outcome.
Time Frame	week 12, week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental	Placebo Comparator
Arm/Group Description	hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX Folic acid Loxoprofen hrIL-2 active: hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)	hrIL-2 placebo (1 million U doses of placebo s.c.injection) MTX Folic acid Loxoprofen hrIL-2 placebo: hrIL-2 placebo (1 million U doses of hrIL-2 placebo s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)
Measure Participants	17	23
week 24	15.29	6.90
week 12	24.32	27.25

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental, Placebo Comparator
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.085
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

14. Secondary Outcome

Title	Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]
Description	The Arthritis interference in the last month with work productivity is measured on a scale that ranges from 0 (no interference) to 10 (complete interference). The Arthritis interference in the last month with household work productivity is measured on a scale that ranges from 0 (no interference) to 10 (complete interference).higher scores mean a worse outcome.
Time Frame	week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental	Placebo Comparator
Arm/Group Description	hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX Folic acid Loxoprofen hrIL-2 active: hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)	hrIL-2 placebo (1 million U doses of placebo s.c.injection) MTX Folic acid Loxoprofen hrIL-2 placebo: hrIL-2 placebo (1 million U doses of hrIL-2 placebo s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)
Measure Participants	23	24
rate of Arthritis interference	3	2
Rate of arthritis interference with household work	5	5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental, Placebo Comparator
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.740
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

15. Secondary Outcome

Title	Erythrocyte Sedimentation Rate (ESR)
Time Frame	week 12, week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental	Placebo Comparator
Arm/Group Description	hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX Folic acid Loxoprofen hrIL-2 active: hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)	hrIL-2 placebo (1 million U doses of placebo s.c.injection) MTX Folic acid Loxoprofen hrIL-2 placebo: hrIL-2 placebo (1 million U doses of hrIL-2 placebo s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)
Measure Participants	17	23
Week 24	43.3 (25.9)	36.8 (24.9)
Week 12	29.6 (25.6)	28.3 (21.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental, Placebo Comparator
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.881
	Comments
	Method	Mixed Models Analysis
	Comments

16. Secondary Outcome

Title	C Reactive Protein (CRP)
Time Frame	week 12, week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental	Placebo Comparator
Arm/Group Description	hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX Folic acid Loxoprofen hrIL-2 active: hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)	hrIL-2 placebo (1 million U doses of placebo s.c.injection) MTX Folic acid Loxoprofen hrIL-2 placebo: hrIL-2 placebo (1 million U doses of hrIL-2 placebo s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)
Measure Participants	17	23
week 24	21.6 (20.83)	15.32 (14.74)
week 12	9.5 (9.0)	7.8 (7.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental, Placebo Comparator
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.422
	Comments
	Method	Mixed Models Analysis
	Comments

17. Secondary Outcome

Title	The Change From Baseline of Patient's Global Assessment of Disease Activity (PtGADA)
Description	VAS score from 0 to 100 for Patient's Global Assessment of Disease Activity Higher scores mean a worse outcome. The change from baseline of PtGADA, the minimum is -100, the maximum is 100. Higher scores mean a worse outcome.
Time Frame	week 12, week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental	Placebo Comparator
Arm/Group Description	hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX Folic acid Loxoprofen hrIL-2 active: hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)	hrIL-2 placebo (1 million U doses of placebo s.c.injection) MTX Folic acid Loxoprofen hrIL-2 placebo: hrIL-2 placebo (1 million U doses of hrIL-2 placebo s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)
Measure Participants	17	23
week 24	-57.5	-33.3
week 12	-57.1	-33.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental, Placebo Comparator
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.055
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

18. Secondary Outcome

Title	The Change From Baseline of Physician's Global Assessment of Disease Activity (PhGADA)
Description	VAS score from 0 to 100 for Physician's Global Assessment of Disease Activity higher scores mean a worse outcome. The change from baseline, the minimum is -100, the maximum is 100.
Time Frame	week 12, week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental	Placebo Comparator
Arm/Group Description	hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX Folic acid Loxoprofen hrIL-2 active: hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)	hrIL-2 placebo (1 million U doses of placebo s.c.injection) MTX Folic acid Loxoprofen hrIL-2 placebo: hrIL-2 placebo (1 million U doses of hrIL-2 placebo s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)
Measure Participants	17	23
week 24	-58.3	-44.4
week 12	-57.1	-25.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental, Placebo Comparator
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.039
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

19. Secondary Outcome

Title	The Change From Baseline of Patient's Assessment of Arthritis Pain (PtAAP)
Description	VAS score from 0 to 100 for Patient's Assessment of Arthritis Pain higher scores mean a worse outcome. The change from baseline of PtAAP, the minimum is -100, the maximum is 100.
Time Frame	week 12, week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental	Placebo Comparator
Arm/Group Description	hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX Folic acid Loxoprofen hrIL-2 active: hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)	hrIL-2 placebo (1 million U doses of placebo s.c.injection) MTX Folic acid Loxoprofen hrIL-2 placebo: hrIL-2 placebo (1 million U doses of hrIL-2 placebo s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)
Measure Participants	17	23
week 24	-57.5	-33.3
week 12	-57.1	-27.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental, Placebo Comparator
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.156
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

20. Secondary Outcome

Title	Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]-2
Description	In the last month, number of work days missed, number of work days with reduced productivity. In the last month, number of days with no household work, number of days with reduced household work productivity, number of days with hired outside help, number of days missed of family/social/leisure activities in the last month.higher scores mean a worse outcome.
Time Frame	week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental	Placebo Comparator
Arm/Group Description	hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX Folic acid Loxoprofen hrIL-2 active: hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)	hrIL-2 placebo (1 million U doses of placebo s.c.injection) MTX Folic acid Loxoprofen hrIL-2 placebo: hrIL-2 placebo (1 million U doses of hrIL-2 placebo s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)
Measure Participants	23	24
number of work days with reduced productivity	3.5	0
number of work days missed	0	0
Household work days missed due to arthritis	0	0
Days with household work productivity reduced	15	12
Days with activities missed due to arthritis	5	0
Days with outside help hired due to arthritis	0	0

Adverse Events

Arm/Group Title	Experimental		Placebo Comparator
Arm/Group Description	hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX Folic acid Loxoprofen hrIL-2 active: hrIL-2 active (1 million U doses of hrIL-2s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)		hrIL-2 placebo (1 million U doses of placebo s.c.injection) MTX Folic acid Loxoprofen hrIL-2 placebo: hrIL-2 placebo (1 million U doses of hrIL-2 placebo s.c.injection) MTX: Methotrexate (oral administration) Folic Acid: Folic Acid (oral administration) Loxoprofen: Loxoprofen (oral administration)
All Cause Mortality
	Experimental		Placebo Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/23 (47.8%)		9/24 (37.5%)
Serious Adverse Events
	Experimental		Placebo Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/23 (8.7%)		1/24 (4.2%)
Surgical and medical procedures
Hospitalized not related to RA	2/23 (8.7%)	2	1/24 (4.2%)	1
Other (Not Including Serious) Adverse Events
	Experimental		Placebo Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/23 (39.1%)		8/24 (33.3%)
Gastrointestinal disorders
gastrointestinal disorders	2/23 (8.7%)	2	1/24 (4.2%)	1
Hepatobiliary disorders
Hepatic enzyme increased	1/23 (4.3%)	1	1/24 (4.2%)	1
Immune system disorders
Worsening of RA	1/23 (4.3%)	1	3/24 (12.5%)	3
Infections and infestations
Upper respiratory tract infection	1/23 (4.3%)	1	1/24 (4.2%)	1
Injury, poisoning and procedural complications
Fever after injection	2/23 (8.7%)	2	0/24 (0%)	0
Skin and subcutaneous tissue disorders
Injection site reactions	3/23 (13%)	3	2/24 (8.3%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT 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.