Trial Outcomes & Findings for To Evaluate the Immunogenicity and Safety of Sarilumab Administered as Monotherapy in Patients With Rheumatoid Arthritis (RA) (NCT NCT02121210)
NCT ID: NCT02121210
Last Updated: 2017-06-20
Results Overview
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.
COMPLETED
PHASE3
132 participants
From Baseline to Week 30 [End of study (EOS)]
2017-06-20
Participant Flow
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.
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.
Participant milestones
| Measure |
Sarilumab 150 mg q2w
Sarilumab 150 mg subcutaneous (SC) injection q2w for 24 weeks
|
Sarilumab 200 mg q2w
Sarilumab 200 mg SC injection q2w for 24 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
65
|
67
|
|
Overall Study
COMPLETED
|
58
|
58
|
|
Overall Study
NOT COMPLETED
|
7
|
9
|
Reasons for withdrawal
| Measure |
Sarilumab 150 mg q2w
Sarilumab 150 mg subcutaneous (SC) injection q2w for 24 weeks
|
Sarilumab 200 mg q2w
Sarilumab 200 mg SC injection q2w for 24 weeks.
|
|---|---|---|
|
Overall Study
Adverse Event
|
5
|
7
|
|
Overall Study
Lack of Efficacy
|
2
|
0
|
|
Overall Study
Other than specified above
|
0
|
2
|
Baseline Characteristics
To Evaluate the Immunogenicity and Safety of Sarilumab Administered as Monotherapy in Patients With Rheumatoid Arthritis (RA)
Baseline characteristics by cohort
| Measure |
Sarilumab 200 mg q2w
n=67 Participants
Sarilumab 200 mg SC injection q2w for 24 weeks.
|
Total
n=132 Participants
Total of all reporting groups
|
Sarilumab 150 mg q2w
n=65 Participants
Sarilumab 150 mg SC injection q2w for 24 weeks.
|
|---|---|---|---|
|
Age, Continuous
|
53.6 years
STANDARD_DEVIATION 14.1 • n=7 Participants
|
52.4 years
STANDARD_DEVIATION 13.4 • n=5 Participants
|
51.1 years
STANDARD_DEVIATION 12.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
57 Participants
n=7 Participants
|
106 Participants
n=5 Participants
|
49 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
16 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From Baseline to Week 30 [End of study (EOS)]Population: 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.
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.
Outcome measures
| Measure |
Sarilumab 150 mg q2w
n=65 Participants
Sarilumab 150 mg SC injection q2w for 24 weeks.
|
Sarilumab 200 mg q2w
n=66 Participants
Sarilumab 200 mg SC injection q2w for 24 weeks.
|
|---|---|---|
|
Percentage of Participants With Incidence of Antidrug Antibodies (ADA)
Overall positive
|
24.6 Percentage of participants
|
18.2 Percentage of participants
|
|
Percentage of Participants With Incidence of Antidrug Antibodies (ADA)
Persistent positive
|
12.3 Percentage of participants
|
6.1 Percentage of participants
|
|
Percentage of Participants With Incidence of Antidrug Antibodies (ADA)
Persistent neutralizing positive
|
10.8 Percentage of participants
|
3.0 Percentage of participants
|
SECONDARY outcome
Timeframe: Pre-dose at Week 0 (Baseline), 2, 4, 12, 16, 20, 24 and 30Population: 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.
Trough Concentration (Ctrough).
Outcome measures
| Measure |
Sarilumab 150 mg q2w
n=54 Participants
Sarilumab 150 mg SC injection q2w for 24 weeks.
|
Sarilumab 200 mg q2w
n=52 Participants
Sarilumab 200 mg SC injection q2w for 24 weeks.
|
|---|---|---|
|
Serum Sarilumab Concentration
|
7350 ng/mL
Standard Deviation 8030
|
17200 ng/mL
Standard Deviation 15900
|
Adverse Events
Sarilumab 150mg q2w
Sarilumab 200mg q2w
Serious adverse events
| Measure |
Sarilumab 150mg q2w
n=65 participants at risk
Sarilumab 150 mg SC injection q2w for 24 weeks.
|
Sarilumab 200mg q2w
n=67 participants at risk
Sarilumab 200 mg SC injection q2w for 24 weeks.
|
|---|---|---|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/65 • 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.
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.
|
1.5%
1/67 • 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.
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.
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
1.5%
1/65 • 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.
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.
|
0.00%
0/67 • 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.
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.
|
|
Injury, poisoning and procedural complications
Laceration
|
0.00%
0/65 • 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.
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.
|
1.5%
1/67 • 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.
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.
|
Other adverse events
| Measure |
Sarilumab 150mg q2w
n=65 participants at risk
Sarilumab 150 mg SC injection q2w for 24 weeks.
|
Sarilumab 200mg q2w
n=67 participants at risk
Sarilumab 200 mg SC injection q2w for 24 weeks.
|
|---|---|---|
|
Infections and infestations
Upper respiratory tract infection
|
4.6%
3/65 • 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.
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.
|
6.0%
4/67 • 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.
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.
|
|
Infections and infestations
Urinary tract infection
|
3.1%
2/65 • 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.
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.
|
6.0%
4/67 • 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.
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.
|
|
Blood and lymphatic system disorders
Neutropenia
|
12.3%
8/65 • 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.
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.
|
16.4%
11/67 • 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.
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.
|
|
Vascular disorders
Hypertension
|
0.00%
0/65 • 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.
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.
|
6.0%
4/67 • 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.
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.
|
|
General disorders
Injection site erythema
|
7.7%
5/65 • 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.
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.
|
3.0%
2/67 • 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.
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.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER