SKYPP: An Open-label, Ascending, Repeated Dose-finding Study of Sarilumab in Children and Adolescents With Polyarticular-course Juvenile Idiopathic Arthritis (pcJIA)

• Sponsor: Sanofi (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02776735
• Collaborator: Regeneron Pharmaceuticals (Industry)
• Enrollment: 100
• Locations: 35
• Arm: 1
• Anticipated Duration (Months): 87.7
• Patients Per Site: 2.9
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Primary Objective:

To describe the pharmacokinetic (PK) profile of sarilumab in patients aged 2-17 years with Polyarticular-course Juvenile Idiopathic Arthritis (pcJIA) in order to identify the dose and regimen for adequate treatment of this population

Secondary Objective:

To describe the pharmacodynamic (PD) profile, the efficacy and the long-term safety of sarilumab in patients with pcJIA.

Condition or Disease	Intervention/Treatment	Phase
Juvenile Idiopathic Arthritis	Drug: Sarilumab	Phase 2

Detailed Description

For approximately 72 patients enrolled in the dose-finding and second portions, the total study duration per patient will be 166 weeks that will consist of a 4- week screening, a 12-week core treatment phase, a 144-week extension phase, and a 6-week post-treatment follow-up. For approximately 28 patients enrolled in the third portion, the total study duration per patient will be 106 weeks that will consist of a 4- week screening, a 12-week core treatment phase, a 84-week extension phase, and a 6-week post-treatment follow-up.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 100 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Sequential, Ascending, Repeated Dose-finding Study of Sarilumab, Administered With Subcutaneous (SC) Injection, in Children and Adolescents, Aged 2 to 17 Years, With Polyarticular-course Juvenile Idiopathic Arthritis (pcJIA) Followed by an Extension Phase
• Actual Study Start Date: Sep 6, 2016
• Actual Primary Completion Date: Apr 8, 2022
• Anticipated Study Completion Date: Dec 28, 2023

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Sarilumab Participants will receive one of three ascending dose regimens of sarilumab by subcutaneous (SC) injection based on body weight. All the participants will receive the selected dose regimen once this is identified. Sarilumab will be given during 12-week core treatment phase followed by an extension treatment phase (144 weeks for approximately 72 patients enrolled in dose-finding and second portions and 84 weeks for approximately 28 patients enrolled in third portion)

Drug: Sarilumab; Pharmaceutical form:Solution Route of administration: Subcutaneous; Other Names: SAR153191 (REGN88)

Outcome Measures

Primary Outcome Measures

1. Assessment of PK parameter: maximum serum concentration observed (Cmax) [Up to Week 12]

2. Assessment of PK parameter: Area under the serum concentration versus time curve calculated using the trapezoidal method during a dose interval (AUC0-t) [Up to Week 12]

3. Assessment of PK parameter: Concentration observed before treatment administration during repeated dosing (Ctrough) [Up to Week 12]

Secondary Outcome Measures

1. Number of patients with adverse events [Core treatment phase: Up to Week(W) 12. Extension phase: Up to end of study (W162 for dose-finding and second portions or W102 for third portion)]

2. Number of patients with local site reactions [Core treatment phase: Up to Week 12. Extension phase: Up to end of treatment (W156 for dose-finding and second portions or W96 for third portion)]

3. Juvenile Idiopathic Arthritis (JIA ACR) 30/50/70/90/100 response rate [Core treatment phase: Up to Week 12. Extension phase: up to W156 for dose-finding and second portions or W96 for third portion]

4. Change from baseline in JIA ACR Component: Physician's global assessment of disease activity [Core treatment phase: Up to Week 12. Extension phase: up to W156 for dose-finding and second portions or W96 for third portion]

5. Change from baseline in JIA ACR Component: Patient / parent assessment of overall well-being [Core treatment phase: Up to Week 12. Extension phase: up to W156 for dose-finding and second portions or W96 for third portion]

6. Change from baseline in JIA ACR Component: Childhood Health Assessment Questionnaire (CHAQ) - Disability Index [Core treatment phase: Up to Week 12. Extension phase: up to W156 for dose-finding and second portions or W96 for third portion]

7. Change from baseline in JIA ACR Component: Number of joints with active arthritis [Core treatment phase: Up to Week 12. Extension phase: up to W156 for dose-finding and second portions or W96 for third portion]

8. Change from baseline in JIA ACR Component: Number of joints with limitation of motion [Core treatment phase: Up to Week 12. Extension phase: up to W156 for dose-finding and second portions or W96 for third portion]

9. Change from baseline in JIA ACR Component: High sensitivity C-reactive protein (hs-CRP) [Core treatment phase: Up to Week 12. Extension phase: up to W156 for dose-finding and second portions or W96 for third portion]

10. Change from baseline in Juvenile Arthritis Disease Activity Score-27 (JADAS) [Core treatment phase: Up to Week 12. Extension phase: up to W156 for dose-finding and second portions or W96 for third portion]

11. Change in IL-6 associated biomarkers: IL6 [Up to Week 12]

12. Change in IL-6 associated biomarkers: sIL-6R [Up to Week 12]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria :

• Male and female patients aged ≥2 and ≤17 years (or country specified age requirement) at the time of the screening visit.

• Diagnosis of rheumatoid factor-negative or rheumatoid factor positive polyarticular Juvenile Idiopathic Arthritis (JIA) subtype or oligoarticular extended JIA subtype according to the International League of Associations for Rheumatology (ILAR) 2001 Juvenile Idiopathic Arthritis Classification Criteria with at least 5 active joints as per American College of Rheumatology (ACR) definition for "active arthritis" at Screening

• Patient with an inadequate response to current treatment and considered as a candidate for a biologic disease modifying antirheumatic drug (DMARD) as per investigator's judgment

Exclusion criteria:

• Body weight <10 kg or >60 kg for patients enrolled in the 3 ascending dose cohorts, then body weight <10 kg for patients subsequently enrolled at the selected dose-regimen.

• If nonsteroidal anti-inflammatory drugs (NSAIDs) [including cyclo oxygenase-2 inhibitors (COX-2)] taken, dose stable for <2 weeks prior to the baseline visit and/or dosing prescribed outside of approved label.

• If non-biologic DMARD taken, dose stable for <6 weeks prior to the baseline visit or at a dose exceeding the recommended dose as per local labeling.

• If oral glucocorticoid taken, dose exceeding equivalent prednisone dose 0.5 mg/kg/day (or 30 mg/day) within 2 weeks prior to baseline.

• Use of parenteral or intra-articular glucocorticoid injection within 4 weeks prior to baseline.

• Prior treatment with anti-interleukin 6 (IL-6) or IL-6 receptor (IL-6R) antagonist therapies, including but not limited to tocilizumab or sarilumab.

• Treatment with any biologic treatment for pcJIA within 5 half-lives prior to the first dose of sarilumab.

• Treatment with a Janus kinase inhibitor within 4 weeks prior to the first dose of sarilumab; and treatment with growth hormone within 4 weeks prior to the first dose of sarilumab (the required off treatment periods and procedures may vary according to local requirements).

• Treatment with any investigational biologic or non-biologic product within 8 weeks or 5 half-lives prior to baseline, whichever is longer.

• Lipid lowering drug stable for less than 6 weeks prior to screening.

• Exclusion related to tuberculosis (TB).

• Exclusion criteria related to past or current infection other than tuberculosis.

• Any live, attenuated vaccine within 4 weeks prior to the baseline visit, such as varicella-zoster, oral polio, rubella vaccines. Killed or inactive vaccine may be permitted based on the Investigator's judgment.

• Exclusion related to history of a systemic hypersensitivity reaction to any biologic drug and known hypersensitivity to any constituent of the product.

• Laboratory abnormalities at the screening visit (identified by the central laboratory).

• Pregnant or breast-feeding female adolescent patients.

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	Investigational Site Number :8400416	Los Angeles	California	United States	90027
2	Investigational Site Number :8400415	Jacksonville	Florida	United States	32209
3	Investigational Site Number :8400417	New York	New York	United States	10032
4	Investigational Site Number :8400418	Cincinnati	Ohio	United States	45229-3039
5	Investigational Site Number :0320060	Caba	Buenos Aires	Argentina	C1270AAN
6	Investigational Site Number :0320004	Tucumán		Argentina	T4000AXL
7	Investigational Site Number :1240110	Calgary	Alberta	Canada	T3B 6A8
8	Investigational Site Number :1240112	Montréal	Quebec	Canada	H3T1C5
9	Investigational Site Number :1520016	Concepcion	Biobío	Chile
10	Investigational Site Number :2030041	Brno		Czechia	62500
11	Investigational Site Number :2460040	Helsinki		Finland	00029 HUS
12	Investigational Site Number :2500040	Paris		France	75015
13	Investigational Site Number :2760064	Berlin		Germany	13125
14	Investigational Site Number :2760061	Bremen		Germany	28205
15	Investigational Site Number :2760062	Hamburg		Germany	22081
16	Investigational Site Number :3800051	Genova		Italy	16147
17	Investigational Site Number :3800053	Milano		Italy	20122
18	Investigational Site Number :3800052	Roma		Italy
19	Investigational Site Number :4840060	Monterrey	Nuevo León	Mexico	64460
20	Investigational Site Number :4840061	Jalisco		Mexico	44620
21	Investigational Site Number :5280020	Utrecht		Netherlands	3584 EA
22	Investigational Site Number :6160074	Bydgoszcz	Kujawsko-pomorskie	Poland	85-667
23	Investigational Site Number :6160070	Lublin	Lubuskie	Poland	20-093
24	Investigational Site Number :6160071	Lodz	Lódzkie	Poland	91-738
25	Investigational Site Number :6160073	Krakow	Malopolskie	Poland	31-503
26	Investigational Site Number :6160072	Sosnowiec	Slaskie	Poland	41-218
27	Investigational Site Number :6430001	Moscow		Russian Federation	115522
28	Investigational Site Number :6430062	Moscow		Russian Federation	117198
29	Investigational Site Number :6430063	Moscow		Russian Federation	119991
30	Investigational Site Number :7240050	Esplugues de Llobregat	Castilla Y León	Spain	08950
31	Investigational Site Number :7240052	Madrid	Madrid, Comunidad De	Spain	28046
32	Investigational Site Number :7240053	Madrid		Spain	28009
33	Investigational Site Number :7240051	Valencia		Spain	46026
34	Investigational Site Number :8260031	London	London, City Of	United Kingdom	WC1N 3JH
35	Investigational Site Number :8260033	Liverpool		United Kingdom	L12 2AP

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: NCT02776735
• Other Study ID Numbers: DRI13925; 2015-003999-79; U1111-1177-3487
• First Posted: May 18, 2016
• Last Update Posted: May 12, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Arthritis; Arthritis, Juvenile

Study Results

No Results Posted as of May 12, 2022