Clinical trial NCT05814159: A Study of Anakinra in Japanese Patients With Still's Disease (SJIA and AOSD)
Official title: A Randomized, Double-blind, Placebo-controlled, Multicenter, Phase 3 Efficacy and Safety Study of Subcutaneous Anakinra in Japanese Patients With Still's Disease (SJIA and AOSD)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Still's Disease, Juvenile Onset
Still's Disease, Adult-Onset
Lead sponsor: Swedish Orphan Biovitrum
Sponsor class: INDUSTRY
Collaborators: name: CMIC Co, Ltd. Japan
First posted: 2023-04-14
Enrollment: 15
Sex: ALL
Minimum age (years): 8
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A study to demonstrate efficacy and safety of anakinra in pediatric and adult Japanese patients with Still's disease (Systemic juvenile idiopathic arthritis \[SJIA\] and Adult-onset Still's disease \[AOSD\]).

Detailed description: The study consists of two phases:

• Core phase comprising 2 weeks double blind placebo-controlled treatment, 52 weeks open label treatment and 4 weeks safety follow up (only for patients not entering the extension phase).

At the Week 54 visit, patients who consent and are eligible to continue anakinra treatment, will enter the extension phase and continue open label anakinra treatment.

• Extension phase comprising up to 26 weeks open label treatment and 4 weeks safety follow up.

The primary endpoint will be evaluated at Week 2 visit.

Eligibility criteria: Key Inclusion Criteria:

1. Male and female patients, 8 months of age or older with a body weight ≥ 10 kg
2. Diagnosis of Still's disease
3. If \< 16 years of age at disease onset, the diagnosis is madeaccording to adapted ILAR criteria i.e., CARRA criteria for SJIA. If ≥ 16 years of age at disease onset, the diagnosis is made according to Yamaguchi criteria for AOSD.
4. Active disease confirmed by the following three signs and symptoms. a. Active arthritis in ≥ 1 joint. b. CRP \> 30 mg/L. c. At least one fever episode (≥ 38.0 degree Celsius) attributable to the disease within one week before enrollment.
5. The result of tuberculosis test within 8 weeks prior to enrollment is negative.

Key Exclusion Criteria:

1. Previous or current treatment with anakinra, or any other Interleukin-1 (IL-1) inhibitor except for canakinumab. Previous treatment with canakinumab is allowed if canakinumab was discontinued for reasons other than lack of efficacy and after a washout period of minimum 130 days. Patients who have discontinued canakinumab because of insufficient effect or refractory disease are not allowed to be enrolled in the study.
2. Use of the following therapies prior to enrollment.

   1. Narcotic analgesics within 24 hours prior to enrollment.
   2. Diaminodiphenyl sulfone within 1 week prior to enrollment or etanercept within 2 weeks prior to enrollment.
   3. Intraarticular, intramuscular, or intravenous administration of glucocorticoids within 72h(3 days) prior to enrollment, or intravenous immunoglobulin within 4 weeks prior to enrollment.
   4. Intravenous immunoglobulins with proven Still's disease modifying effect, leflunomide, infliximab, or adalimumab within 8 weeks prior to enrollment.
   5. Thalidomide within 72h(3 days) prior to enrollment, cyclosporine within 5 weeks prior to enrollment, mycophenolate mofetil within 1 week prior to enrollment, 6-mercaptopurine within 48h(2 days) prior to enrollment, azathioprine within 72h(3 days) prior to enrollment, cyclophosphamide within 96h(4 days) prior to enrollment, chlorambucil (not approved inJapan) within 48h(2 days) prior to enrollment, or any other immunosuppressants within 12 weeks prior to enrollment.
   6. Tocilizumab within 4 weeks prior to enrollment or any other immunomodulatory medications within 4 half-lives prior to enrollment.
   7. Rituximab within 13 weeks prior to enrollment.
   8. Canakinumab within 130 days prior to enrollment
3. Live vaccines within 4 weeks prior to enrollment.
4. Known presence or suspicion of active, chronic, or recurrent bacterial, fungal, or viral infections, including but not limited to tuberculosis, HIV infection, Covid-19 infection, or hepatitis B or C infection at baseline. Patients with acute or chronic HBV.
5. Clinical evidence of liver disease or liver injury as indicated by presence of abnormal liver tests.
6. Presence of severe chronic kidney disease (CKD) grades 4 and 5.
7. Presence of neutropenia (absolute neutrophil count \[ANC\] \< 1.5 x 10\^9/L).
8. Presence of thrombocytopenia (platelets count \< 100 x 10\^9/L).
9. Presence or suspicion of MAS at baseline.
10. History or diagnosis of MAS within the last 4 weeks prior to enrollment.

After completion of the study Core Phase, patients who consent and are eligible to continue anakinra treatment, can enter the extension phase .

Primary outcomes:
measure: An improvement of ≥ 30% from baseline in physician global assessment of disease activity (visual analogue scale [VAS]).
timeFrame: Week 2
measure: An improvement of ≥ 30% from baseline in patient/parent global assessment of overall well-being (VAS).
timeFrame: Week 2
measure: An improvement of ≥ 30% from baseline in number of joints with active arthritis.
timeFrame: Week 2
measure: An improvement of ≥ 30% from baseline in number of joints with limitation of motion.
timeFrame: Week 2
measure: An improvement of ≥ 30% from baseline in assessment of physical function: Child health assessment questionnaire (CHAQ)/Stanford health assessment questionnaire (SHAQ).
timeFrame: Week 2
measure: An improvement of ≥ 30% from baseline in C-reactive protein (CRP) (mg/L).
timeFrame: Week 2
Secondary outcomes:
measure: Change in CRP.
timeFrame: Week 2
measure: Change in ferritin.
timeFrame: Week 2
measure: Change in haemoglobin.
timeFrame: Week 2
measure: Change in platelets count.
timeFrame: Week 2
measure: Change in white blood cells count.
timeFrame: Week 2
measure: Absence of fever during the 24 hours preceding the evaluation visit at Week 1.
timeFrame: Week 1
measure: Absence of rash during the 24 hours preceding the evaluation visit at Week 1.
timeFrame: Week 1
measure: ACR30 response with absence of fever during the 24 hours preceding the evaluation visit at Week 1.
timeFrame: Week 1
measure: ACR50 response with absence of fever during the 24 hours preceding the evaluation visit at Week 1.
timeFrame: Week 1
measure: ACR70 response with absence of fever during the 24 hours preceding the evaluation visit at Week 1.
timeFrame: Week 1
measure: Change in physician global assessment of disease activity, measured on a VAS from no pain (0 mm) to very severe (100 mm).
timeFrame: Week 1
measure: Change in patient/parent global assessment of overall well-being, measured on a VAS from no pain (0 mm) to very severe (100 mm).
timeFrame: Week 1
measure: Change in patient/parent global assessment of disease related pain, measured on a VAS from no pain (0 mm) to very severe (100 mm).
timeFrame: Week 1
measure: Change in swelling joints count.
timeFrame: Week 1
measure: Change in tender joints count.
timeFrame: Week 1
measure: Change in CRP.
timeFrame: Week 1
measure: Change in ferritin.
timeFrame: Week 1
measure: Change in haemoglobin.
timeFrame: Week 1
measure: Change in platelets count.
timeFrame: Week 1
measure: Change in white blood cells count.
timeFrame: Week 1
measure: Change in the number/proportion of patients reporting problems by dimension of EQ-5D-Y Proxy (4-7 years).
timeFrame: Week 2
measure: Change in the number/proportion of patients reporting problems by dimension of EQ-5D-Y (8-15 years).
timeFrame: Week 2
measure: Change in the number/proportion of patients reporting problems by dimension of EQ-5D-3L (≥ 16 years).
timeFrame: Week 2
measure: Absence of fever during the 7 days preceding the visit.
timeFrame: Week 4 to Week 54
measure: Absence of rash during the 7 days preceding the visit.
timeFrame: Week 4 to Week 54
measure: ACR30 response with absence of fever during the 7 days preceding the visit.
timeFrame: Week 4 to Week 54
measure: ACR50 response with absence of fever during the 7 days preceding the visit.
timeFrame: Week 4 to Week 54
measure: ACR70 response with absence of fever during the 7 days preceding the visit.
timeFrame: Week 4 to Week 54
measure: ACR90 response with absence of fever during the 7 days preceding the visit.
timeFrame: Week 4 to Week 54
measure: Change in physician global assessment of disease activity (VAS).
timeFrame: Week 4 to Week 54
measure: Change in patient/parent global assessment of overall well-being (VAS).
timeFrame: Week 4 to Week 54
measure: Change in patient/parent global assessment of disease related pain (VAS).
timeFrame: Week 4 to Week 54
measure: Change in swelling joints count.
timeFrame: Week 4 to Week 54
measure: Change in tender joints count.
timeFrame: Week 4 to Week 54
measure: Change in CRP.
timeFrame: Week 4 to Week 54
measure: Change in ferritin.
timeFrame: Week 4 to Week 54
measure: Change in haemoglobin.
timeFrame: Week 4 to Week 54
measure: Change in platelets count.
timeFrame: Week 4 to Week 54
measure: Change in white blood cells count.
timeFrame: Week 4 to Week 54
measure: Occurrence of inactive disease.
timeFrame: Week 8 to Week 54
measure: Change in the number/proportion of patients reporting problems by dimension of EQ-5D-Y Proxy (4-7 years).
timeFrame: Week 4 to Week 54
measure: Change in the number/proportion of patients reporting problems by dimension of EQ-5D-Y (8-15 years).
timeFrame: Week 4 to Week 54
measure: Change in the number/proportion of patients reporting problems by dimension of EQ-5D-3L(≥ 16 years).
timeFrame: Week 4 to Week 54
measure: ACR30 response with absence of fever during the 7 days preceding the study visits over time.
timeFrame: Week 2 to Week 54
measure: To evaluate the occurrence of study drug discontinuation in anakinra treated patients with Still's disease.
timeFrame: Day 1 to Week 54
measure: Time of initiation of glucocorticoids tapering.
timeFrame: Week 2 to Week 54
measure: Percentage decrease of glucocorticoids dose for patients tapering their glucocorticoids dose.
timeFrame: Week 2 to Week 54
measure: Discontinuation of glucocorticoids.
timeFrame: Week 2 to Week 54
measure: - Occurrence of adverse events (AEs) (serious adverse events [SAEs] and non-SAEs).
timeFrame: Baseline to Week 58
measure: Occurrence of deaths
timeFrame: Baseline to Week 58
measure: Occurrence of AEs leading to study drug discontinuation at all study visits.
timeFrame: Baseline to Week 58
measure: Occurrence of vital signs changes from baseline, including blood pressure, heart rate, and body weight at all study visits up to Week 58 visit. Changes of height in patients younger than 19 years old.
timeFrame: Baseline to Week 58
measure: Occurrence of laboratory safety assessments changes over time.
timeFrame: Baseline to Week 58
measure: Occurrence of abnormal laboratory values.
timeFrame: Baseline to Week 58
measure: To evaluate immunogenicity of anakinra in patients with Still's disease.
timeFrame: Baseline, Weeks 2, 4, 12, 34, 54 and 58
measure: To evaluate the pharmacokinetic of anakinra in patients with Still's disease
timeFrame: Baseline, Weeks 1 and 2
Other outcomes:
Locations:
city: Fukushima-shi
country: Japan
facility: Fukushima Medical University Hospital
state: Fukushima
city: Kobe city
country: Japan
facility: Kobe University Hospital
state: Hyogo
city: Kobe
country: Japan
facility: Hyogo Prefectural Kobe Children's Hospital
state: Hyogo
city: Yokohama
country: Japan
facility: Yokohama City University Hospital (Hematology and Clinical Immunology)
state: Kanagawa
city: Matsumoto
country: Japan
facility: Shinshu University
state: Nagano
city: Bunkyō-Ku
country: Japan
facility: Tokyo Medical And Dental University Hospital
state: Tokyo
city: Shinjuku-Ku
country: Japan
facility: Tokyo Women's Medical University Hospital
state: Tokyo
city: Gifu
country: Japan
facility: Gifu University Hospital
Study officials:
affiliation: St. Marianna University Hospital
name: Masaaki Mori, MD
role: PRINCIPAL_INVESTIGATOR
References: