SARIL-RA-ONE: To Evaluate the Immunogenicity and Safety of Sarilumab Administered as Monotherapy in Patients With Rheumatoid Arthritis (RA)

• Sponsor: Sanofi (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02121210
• Collaborator: Regeneron Pharmaceuticals (Industry)
• Enrollment: 132
• Locations: 28
• Arms: 2
• Duration (Months): 11
• Patients Per Site: 4.7
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Primary Objective:

To evaluate the immunogenicity of sarilumab administered as monotherapy.

Secondary Objectives:

• To evaluate the other safety aspects of sarilumab administered as monotherapy.

• To assess the exposure of sarilumab administered as monotherapy.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: sarilumab SAR153191 (REGN88)	Phase 3

Detailed Description

Total study duration was up to 34 weeks: Up to 4-week screening period, 24-week open-label treatment phase, 6-week post-treatment observation. After completion of the treatment phase of this study, participants were eligible to enter a long term safety study (LTS11210 - SARIL-RA-EXTEND) for continuous treatment with sarilumab (SAR153191 [REGN88]).

Study Design

• Study Type: Interventional
• Actual Enrollment: 132 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Randomized, Parallel Group Study Assessing the Immunogenicity and Safety of Sarilumab Administered as Monotherapy in Patients With Active Rheumatoid Arthritis
• Study Start Date: Jun 1, 2014
• Actual Primary Completion Date: May 1, 2015
• Actual Study Completion Date: May 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sarilumab 150 mg q2w Sarilumab 150 mg subcutaneous (SC) injection every two weeks (q2w) for 24 weeks.	Drug: sarilumab SAR153191 (REGN88); Pharmaceutical form: Solution for injection; Route of administration: Subcutaneous
Experimental: Sarilumab 200 mg q2w Sarilumab 200 mg SC injection q2w for 24 weeks.	Drug: sarilumab SAR153191 (REGN88); Pharmaceutical form: Solution for injection; Route of administration: Subcutaneous

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Incidence of Antidrug Antibodies (ADA) [From Baseline to Week 30 [End of study (EOS)]]

   ADA to sarilumab and anti-sarilumab neutralizing antibodies in serum samples were determined using a validated electrochemiluminescence immunoassay method. Percentage of participants with positive ADA during treatment emergent adverse event (TEAE) period (time from first dose of investigational medicinal product [IMP] to last dose of IMP + 60 days) was determined. Persistent ADA Response: treatment-emergent ADA detected at 2 or more consecutive sampling time points during the TEAE period, where the first and last ADA positive samples were separated by a period of at least 16 weeks or if the last measured sample was positive. ADA samples were collected prior to IMP administration at Week 0 (baseline), Week 2, 4, 12, 24 and 30.

Secondary Outcome Measures

1. Serum Sarilumab Concentration [Pre-dose at Week 0 (Baseline), 2, 4, 12, 16, 20, 24 and 30]

   Trough Concentration (Ctrough).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

• Diagnosis of rheumatoid arthritis (RA) ≥ 3 months.

• Moderately to severely active rheumatoid arthritis.

• Participants who per investigator judgment were incomplete responders to at least 12 weeks of an adequate dose of continuous treatment with or who were intolerant of one or a combination of non-biologic disease modifying anti-rheumatic drugs (DMARDs).

Exclusion criteria:

• Participants < 18 years of age.

• Past history of, or current, autoimmune or inflammatory systemic or localized joint disease(s) other than RA.

• History of juvenile idiopathic arthritis or arthritis onset prior to age 16.

• Severe active systemic RA, including but not limited to vasculitis, pulmonary fibrosis, and/or Felty's syndrome.

• Prior treatment with any biologic anti-interleukin 6 (IL-6) or IL-6 receptor (IL-6R) antagonist therapies.

• Treatment with prednisone > 10 mg or equivalent per day, or change in dosage within 4 weeks prior to randomization.

• New treatment with or dose-adjustment of on-going nonsteroidal anti-inflammatory drug (NSAIDs) or cyclooxygenase-2 (COX-2) inhibitors within 4 weeks prior to randomization, except for the use of low-dose acetylsalicylic acid for cardiovascular diseases.

• Use of parenteral glucocorticoids or intra-articular glucocorticoids injection within 4 weeks prior to randomization.

• Prior treatment with a Janus kinase (JAK) inhibitor (tofacitinib).

• New treatment or dose-adjustment to on-going medication for dyslipidemia, such as statin, within 6 weeks prior to randomization.

• Participation in any clinical research study evaluating another investigational drug or therapy within 5 half-lives or 60 days of first dose of study drug administration, whichever is longer.

• Participants with a history of malignancy other than adequately-treated carcinoma in-situ of the cervix, non-metastatic squamous cell or basal cell carcinoma of the skin, within 5 years prior to the randomization visit. Non-malignant lymphoproliferative disorders are also excluded.

• Participants with active tuberculosis or untreated latent tuberculosis infection.

• Pregnant or breast feeding women.

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site Number 840072	Gilbert	Arizona	United States	85234
2	Investigational Site Number 840049	Upland	California	United States	91786
3	Investigational Site Number 840220	South Miami	Florida	United States	33143
4	Investigational Site Number 840230	Elizabethtown	Kentucky	United States	42701
5	Investigational Site Number 840233	Minot	North Dakota	United States	58701
6	Investigational Site Number 840127	Oklahoma City	Oklahoma	United States	73103
7	Investigational Site Number 840011	Tulsa	Oklahoma	United States	74104
8	Investigational Site Number 840009	Duncansville	Pennsylvania	United States	16635
9	Investigational Site Number 840025	Jackson	Tennessee	United States	38305
10	Investigational Site Number 840032	Amarillo	Texas	United States	79124
11	Investigational Site Number 840074	Mesquite	Texas	United States	75150
12	Investigational Site Number 840124	Clarksburg	West Virginia	United States	26301
13	Investigational Site Number 840231	Franklin	Wisconsin	United States	53132
14	Investigational Site Number 152002	Santiago		Chile	7501126
15	Investigational Site Number 203034	Pardubice		Czechia	53002
16	Investigational Site Number 203001	Praha 2		Czechia	12850
17	Investigational Site Number 203002	Uherske Hradiste		Czechia	686 01
18	Investigational Site Number 233010	Tallinn		Estonia	10138
19	Investigational Site Number 233002	Tallinn		Estonia	13419
20	Investigational Site Number 348014	Budapest		Hungary	1027
21	Investigational Site Number 348025	Budapest		Hungary	1027
22	Investigational Site Number 348021	Esztergom		Hungary	2500
23	Investigational Site Number 616018	Poznan		Poland	61-397
24	Investigational Site Number 616031	Warszawa		Poland	01-518
25	Investigational Site Number 616012	Wroclaw		Poland	50-044
26	Investigational Site Number 643006	Kemerovo		Russian Federation	650000
27	Investigational Site Number 643001	Moscow		Russian Federation	115522
28	Investigational Site Number 643016	Ryazan		Russian Federation	390026

Sponsors and Collaborators

• Sanofi
• Regeneron Pharmaceuticals

Investigators

• Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT02121210
• Other Study ID Numbers: EFC13752; 2013-002790-22; U1111-1143-4344
• First Posted: Apr 23, 2014
• Last Update Posted: Jun 20, 2017
• Last Verified: May 1, 2017

• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid

Study Results

Participant Flow

Recruitment Details	The study was conducted at 27 centers in 7 countries. A total of 201 participants were screened between 03 June 2014 and 20 October 2014.
Pre-assignment Detail	Of 201 participants, 69 participants were screen failures due to exclusion criteria met and inclusion criteria not met. 132 participants were randomized in 1:1 ratio to either sarilumab 150 mg every two weeks (q2w) or sarilumab 200 mg q2w.

Arm/Group Title	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Sarilumab 150 mg subcutaneous (SC) injection q2w for 24 weeks	Sarilumab 200 mg SC injection q2w for 24 weeks.
Period Title: Overall Study
STARTED	65	67
COMPLETED	58	58
NOT COMPLETED	7	9

Baseline Characteristics

Arm/Group Title	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w	Total
Arm/Group Description	Sarilumab 150 mg SC injection q2w for 24 weeks.	Sarilumab 200 mg SC injection q2w for 24 weeks.	Total of all reporting groups
Overall Participants	65	67	132
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.1 (12.7)	53.6 (14.1)	52.4 (13.4)
Sex: Female, Male (Count of Participants)
Female	49 75.4%	57 85.1%	106 80.3%
Male	16 24.6%	10 14.9%	26 19.7%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Incidence of Antidrug Antibodies (ADA)
Description	ADA to sarilumab and anti-sarilumab neutralizing antibodies in serum samples were determined using a validated electrochemiluminescence immunoassay method. Percentage of participants with positive ADA during treatment emergent adverse event (TEAE) period (time from first dose of investigational medicinal product [IMP] to last dose of IMP + 60 days) was determined. Persistent ADA Response: treatment-emergent ADA detected at 2 or more consecutive sampling time points during the TEAE period, where the first and last ADA positive samples were separated by a period of at least 16 weeks or if the last measured sample was positive. ADA samples were collected prior to IMP administration at Week 0 (baseline), Week 2, 4, 12, 24 and 30.
Time Frame	From Baseline to Week 30 [End of study (EOS)]

Outcome Measure Data

Analysis Population Description

Analysis was performed on immunogenicity population included all randomized participants who received at least one dose of sarilumab with at least one post-dose, evaluable ADA sample.

Arm/Group Title	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Sarilumab 150 mg SC injection q2w for 24 weeks.	Sarilumab 200 mg SC injection q2w for 24 weeks.
Measure Participants	65	66
Overall positive	24.6 37.8%	18.2 27.2%
Persistent positive	12.3 18.9%	6.1 9.1%
Persistent neutralizing positive	10.8 16.6%	3.0 4.5%

2. Secondary Outcome

Title	Serum Sarilumab Concentration
Description	Trough Concentration (Ctrough).
Time Frame	Pre-dose at Week 0 (Baseline), 2, 4, 12, 16, 20, 24 and 30

Outcome Measure Data

Analysis Population Description

Analysis was performed on pharmacokinetic (PK) population consisted of all randomized population actually received at least one or partial dose of IMP, with at least one post-dose, non-missing serum sarilumab concentration. Number of participants analyzed=participants with serum sarilumab concentration assessment at specified time-points.

Arm/Group Title	Sarilumab 150 mg q2w	Sarilumab 200 mg q2w
Arm/Group Description	Sarilumab 150 mg SC injection q2w for 24 weeks.	Sarilumab 200 mg SC injection q2w for 24 weeks.
Measure Participants	54	52
Mean (Standard Deviation) [ng/mL]	7350 (8030)	17200 (15900)

Adverse Events

Time Frame	All adverse events (AEs) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product.
Adverse Event Reporting Description	Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the time from the first dose of IMP to last dose of IMP + 60 days.
Arm/Group Title	Sarilumab 150mg q2w		Sarilumab 200mg q2w
Arm/Group Description	Sarilumab 150 mg SC injection q2w for 24 weeks.		Sarilumab 200 mg SC injection q2w for 24 weeks.
All Cause Mortality
	Sarilumab 150mg q2w		Sarilumab 200mg q2w
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Sarilumab 150mg q2w		Sarilumab 200mg q2w
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/65 (1.5%)		2/67 (3%)
Blood and lymphatic system disorders
Neutropenia	0/65 (0%)		1/67 (1.5%)
Injury, poisoning and procedural complications
Laceration	0/65 (0%)		1/67 (1.5%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	1/65 (1.5%)		0/67 (0%)
Other (Not Including Serious) Adverse Events
	Sarilumab 150mg q2w		Sarilumab 200mg q2w
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/65 (24.6%)		23/67 (34.3%)
Blood and lymphatic system disorders
Neutropenia	8/65 (12.3%)		11/67 (16.4%)
General disorders
Injection site erythema	5/65 (7.7%)		2/67 (3%)
Infections and infestations
Upper respiratory tract infection	3/65 (4.6%)		4/67 (6%)
Urinary tract infection	2/65 (3.1%)		4/67 (6%)
Vascular disorders
Hypertension	0/65 (0%)		4/67 (6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.