Still's Disease, Adult-OnsetPhase 3anaSTILLsNCT03265132
A Study to Evaluate Efficacy and Safety of Anakinra in the Treatment of Still's Disease (SJIA and AOSD)
A Phase 3 study testing anakinra in people with Still's Disease, Adult-Onset and Still's Disease, Juvenile-Onset, run by Swedish Orphan Biovitrum at 39 sites in 2 countries.
Trial summary
The aim of this study is to demonstrate the efficacy and to evaluate the safety, pharmacokinetics (PK) and immunogenicity of anakinra in patients with newly diagnosed Still's disease, including SJIA (Systemic juvenile idiopathic arthritis) and AOSD (Adult-onset Still's disease). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Still's Disease, Adult-Onset, Still's Disease, Juvenile-Onset
- What is being tested?
- anakinra
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 13 participants
- Where
- 39 sitesin 2 countries
- Study dates
- 26 Sep 2017to 23 May 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Signed informed consent.
- Male and female patients with a body weight ≥ 10 kg.
- Diagnosis of Still's disease.
- If currently on glucocorticoid treatment, a stable dose for at least 1 week prior to randomization.
- If currently on methotrexate treatment, a stable dose for at least 8 weeks prior to randomization.
- Active disease.
- Female patients of childbearing potential must use an effective method of contraception during the study (abstinence being a possible option) as well as present a negative pregnancy test prior to randomization.
- Negative interferon-gamma release assay or Purified protein derivative ( PPD) test within 2 months prior to randomization. If not available, a test should be performed at day of randomization.
Who cannot join
- Diagnosis of Still's disease more than 6 months prior to randomization.
- Previous randomization into this study.
- Participation in another concurrent clinical interventional study within 30 days of randomization.
- Treatment with an investigational drug within 5 half-lives prior to randomization.
- Previous or current treatment with anakinra, canakinumab or any other IL-1 inhibitor.
- Use of the following therapies prior to randomization:
Show all 25Show fewer
- Narcotic analgesics within 24 hours prior to randomization.
- Dapsone or etanercept within 3 weeks prior to randomization.
- Intraarticular, intramuscular or intravenous administration of glucocorticoids or intravenous immunoglobulin (Ig) within 4 weeks prior to randomization.
- Intravenous Ig with proven Still's disease modifying effect, leflunomide, infliximab or adalimumab within 8 weeks prior to randomization.
- Thalidomide, cyclosporine, mycophenolate mofetil, 6-mercaptopurine, azathioprine, cyclophosphamide, chlorambucil or any other immunosuppressant within 12 weeks prior to randomization.
- Tocilizumab within 12 weeks prior to randomization or any other immunomodulatory medication within 4 half-lives prior to randomization
- Rituximab within 26 weeks prior to randomization.
- Live vaccines within 1 month prior to randomization.
- Known presence or suspicion of active, chronic or recurrent bacterial, fungal or viral infections, including tuberculosis, HIV infection or hepatitis B or C infection.
- Clinical evidence of liver disease or liver injury.
- Presence of severe renal function impairment.
- Presence of neutropenia.
- Presence or suspicion of MAS at baseline.
- A diagnosis of MAS within the last 2 months prior to randomization.
- History of malignancy within 5 years.
- Known hypersensitivity to E coli-derived proteins, or any components of Kineret® (anakinra).
- Pregnant or lactating women.
- Foreseeable inability to cooperate with given instructions or study procedures.
- Presence of any medical or psychological condition or laboratory result that in the opinion of the investigator can interfere with the patient's ability to comply with the protocol requirements or makes the patient not appropriate for inclusion to the study and treatment with IMP.
Trial locations and contacts
39 sites in 2 countries.
39 sites in 2 countries
United States36 sites
University of Michigan
Ann Arbor, Michigan, 48109
The Children's Hospital Colorado
Aurora, Colorado, 80045
Attune Health
Beverly Hills, California, 90211
University of Alabama Birmingham
Birmingham, Alabama, 35294
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02115
Boston Children's Hospital
Boston, Massachusetts, 02115
University of Vermont Medical Center
Burlington, Vermont, 05401
UNC Hospitals
Chapel Hill, North Carolina, 27514
MetroHealth System
Cleveland, Ohio, 44109
Nationwide Children's Hospital
Columbus, Ohio, 43205
Baylor Research Institute
Dallas, Texas, 75204
Univ of TX Southwestern Medical Center Dallas - Texas Scottish Rite Hospital for Children
Dallas, Texas, 75219
Duke Children's Hospital and Health Center
Durham, North Carolina, 27710
Saint Paul Rheumatology
Eagan, Minnesota, 55121
University of Florida
Gainesville, Florida, 32611
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Texas Children's Hospital
Houston, Texas, 77030
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
Children's Mercy Hospital and Clinics
Kansas City, Kansas, 67208
University of Louisville School of Medicine Research Foundation
Louisville, Kentucky, 40202
University of Miami
Miami, Florida, 33124
Nicklaus Children's Hospital
Miami, Florida, 33155
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
University of Minnesota
Minneapolis, Minnesota, 55454
Monroe Carell Jr. Children's Hospital at Vanderbilt
Nashville, Tennessee, 37232
Hospital for Special Surgery
New York, New York, 10021
Columbia University Medical Center
New York, New York, 10032
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Virginia Commonwealth University
Richmond, Virginia, 23298
University of Utah Hospitals and Clinics
Salt Lake City, Utah, 84113
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
Rady Children's Hospital & Health Center
San Diego, California, 92123
University of Washington
Seattle, Washington, 98195
Saint Louis University
St Louis, Missouri, 63104
Institute for Rheumatic and Autoimmune Diseases
Summit, New Jersey, 07901
Wake Forest Baptist Brenner Medical Center
Winston-Salem, North Carolina, 27157
Canada3 sites
University of Calgary - Alberta Children's Hospital
Calgary
University of Calgary
Calgary
The Hospital for Sick Children
Toronto
About this study
Official title: A Randomized, Double-blind, Placebo-controlled, Multicenter, Phase 3 Efficacy and Safety Study of 2 Dose Levels of Subcutaneous Anakinra (Kineret®) in Patients With Still's Disease (SJIA and AOSD)
The aim of this study is to demonstrate the efficacy and to evaluate the safety, pharmacokinetics (PK) and immunogenicity of anakinra in patients with newly diagnosed Still's disease, including SJIA (Systemic juvenile idiopathic arthritis) and AOSD (Adult-onset Still's disease).
Read the detailed description
The study consists of a 12-week, randomized, double-blind, placebo controlled period with two dose levels of anakinra and a 4-week safety follow-up after last dose of investigational medicinal product (IMP). The primary endpoint will be evaluated at Week 2. Sustained efficacy and time to study drug discontinuation will be evaluated during the full study period.
A screening visit is optional and may be done to identify patients that could be suitable for the study. During the study 6 visits and 2 telephone contacts are scheduled i.e., Day 1 (baseline visit), Day 4Tel, Week 1, Week 2, Week 4, Week 8, Week 12 and Week 16Tel (End of Study).
Patients will be randomly assigned to study drug, after they meet all of the inclusion criteria and none of the exclusion criteria. Patients will receive treatment for 12 weeks, either anakinra or placebo. Patients will be randomized to anakinra in a dose of either 2 or 4 mg/kg/day, with a maximum dose of 100 or 200 mg once daily, respectively. Patients will be randomized to placebo with corresponding volumes for each of the two anakinra dose levels.
- Being tested
- anakinra, Placebo
- Keywords
- Interleukin 1 receptor antagonist, IL-1 receptor antagonist, Kineret, anakinra, Adult-Onset Still's Disease, Systemic Juvenile Idiopathic Arthritis
- Medical subject headings
- Still's Disease, Adult-Onset, Arthritis, Juvenile
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anakinraBiological
Also called Kineret
sub cutaneous injection
PlaceboDrug
sub cutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| anakinra | Experimental | 2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) Receives: Biological: anakinra |
| Placebo | Placebo comparator | Corresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of ACR30 Responders With Absence of Fever Attributable to the Disease During the 7 Days Preceding Week 2.
ACR30 response is defined as an improvement of ≥ 30% from baseline in at least 3 of any 6 variables listed below. Also no more than 1 of the 6 variables may worsen by >30% from baseline. (ACR: American College of Rheumatology)
- Physician global assessment of disease activity - Assessed on a Visual Analogue Scale (VAS) from no disease activity (0 mm) to very severe disease activity (100 mm).
- Patient/parent global assessment of overall well-being - Assessed on a VAS from very well (0 mm) to very poor (100 mm).
- Number of joints with active arthritis.
- Number of joints with limitation of motion.
- Assessment of physical function - Patient Reported Outcome instruments : Childhood Health Assessment Questionnaire (CHAQ) /Stanford Health Assessment Questionnaire (SHAQ).
- C-Reactive Protein (CRP) (mg/L).
Measured: Week 2
Secondary outcomes (49)
Proportion of ACR30 Responders With Absence of Fever During 24 Hours Preceding Week 1.
ACR30 response is defined as an improvement of ≥ 30% from baseline in at least 3 of any 6 variables listed in the description of the primary outcome measure. Also no more than 1 of the 6 variables may worsen by >30% from baseline.
Measured: Week 1
Proportion of ACR50 Responders With Absence of Fever During 24 Hours Preceding Week 1.
ACR50 response is defined as an improvement of ≥ 50% from baseline in at least 3 of any 6 variables listed in the description of the primary outcome measure. Also no more than 1 of the 6 variables may worsen by >30% from baseline.
Measured: Week 1
Proportion of ACR70 Responders With Absence of Fever During 24 Hours Preceding Week 1.
ACR70 response is defined as an improvement of ≥ 70% from baseline in at least 3 of any 6 variables listed in the description of the primary outcome measure. Also no more than 1 of the 6 variables may worsen by >30% from baseline.
Measured: Week 1
Proportion of ACR90 Responders With Absence of Fever During 24 Hours Preceding Week 1.
ACR90 response is defined as an improvement of ≥ 90% from baseline in at least 3 of any 6 variables listed in the description of the primary outcome measure. Also no more than 1 of the 6 variables may worsen by >30% from baseline.
Measured: Week 1
Proportion of ACR50 Responders With Absence of Fever During 7 Days Preceding Week 2.
ACR50 response is defined as an improvement of ≥ 50% from baseline in at least 3 of any 6 variables listed in the description of the primary outcome measure. Also no more than 1 of the 6 variables may worsen by >30% from baseline.
Measured: Week 2
Proportion of ACR70 Responders With Absence of Fever During 7 Days Preceding Week 2.
ACR70 response is defined as an improvement of ≥ 70% from baseline in at least 3 of any 6 variables listed in the description of the primary outcome. Also no more than 1 of the 6 variables may worsen by >30% from baseline.
Measured: Week 2
Proportion of ACR90 Responders With Absence of Fever During 7 Days Preceding Week 2.
ACR90 response is defined as an improvement of ≥ 90% from baseline in at least 3 of any 6 variables listed in the description of the primary outcome . Also no more than 1 of the 6 variables may worsen by >30% from baseline.
Measured: Week 2
Proportion of Responders in Physician Global Assessment of Disease Activity.
Assessed on a VAS from no disease activity (0 mm) to very severe disease activity (100 mm). Response is defined as an improvement of ≥ 30%, 50%, 70% and 90% from baseline. Only improvement of ≥90% at Week 2 reported here.
Measured: Week 2
Proportion of Responders in Patient/Parent Global Assessment of Overall Well-being.
Assessed on a VAS from very well (0 mm) to very poor. (100 mm). Response is defined as an improvement of ≥ 30%, 50%, 70% and 90% from baseline.Only improvement of ≥90% at Week 2 reported here.
Measured: Week 2
Proportion of Responders in Number of Joints With Active Arthritis.
Response is defined as an improvement of ≥ 30%, 50%, 70% and 90% from baseline.Only improvement of ≥90% at Week 2 reported here.
Measured: Week 2
Proportion of Responders in Number of Joints With Limitation of Motion.
Response is defined as an improvement of ≥ 30%, 50%, 70% and 90% from baseline.Only improvement of ≥90% at Week 2 reported here.
Measured: Week 2
Proportion of Responders in Assessment of Physical Function (CHAQ/SHAQ).
Childhood Health Assessment Questionnaire (CHAQ) and Stanford Health Assessment Questionnaire (SHAQ) assess physical and functional status (see Clinical protocol section 6.5.4.1.5). Response is defined as an improvement of ≥ 30%, 50%, 70% and 90% from baseline. Only improvement of ≥90% at Week 2 reported here.
Measured: Week 2
Proportion of Responders in CRP (mg/L).
Response is defined as an improvement of ≥ 30%, 50%, 70% and 90% from baseline. Only improvement of ≥90% at Week 2 reported here.
Measured: Week 2
Proportion of Patients With Absence of Fever During the 7 Days Preceding Week 2.
Proportion of patients with absence of fever during the 7 days preceding Week 2.
Measured: Week 2
Proportion of Patients With Absence of Fever During the 24 Hours Preceding Week 1.
Absence of fever during the 24 hours preceding week 1.
Measured: Week 1
Change From Baseline in Physician Global Assessment of Disease Activity at Week 1.
Change from baseline in Physician global assessment of disease activity measured on a VAS 0 (very well)-100 (very poor) at Week 1.
Measured: Day 1 and Week 1
Change From Baseline in Patient/Parent Global Assessment of Overall Well-being at Week 1.
Change from baseline in patient/parent global assessment of overall well-being measured on a VAS 0 (very well)-100 (very poor) at Week 1.
Measured: Day 1 and Week 1
Change From Baseline in CRP.
Change from baseline in C-Reactive Protein (CRP). CRP is measured in mg/L.
Measured: Day 1 and Week 1
Proportion of Patients With Sustained ACR30, ACR50, ACR70 and ACR90 Response.
Proportion of patients that still meet the corresponding week 2 response with absence of fever in the preceding 7 days. Only the strictest criteria, ACR90, is reported here.
Measured: Week 12
Proportion of Patients With Sustained ACR30, ACR50, ACR70 and ACR90 Response in Relation to Glucocorticoid Tapering.
Please note no patients were treated with any systemic glucocorticoids at randomization. Hence no results available.
Measured: Week 2, Week 4, Week 8 and Week 12
Proportion of Patients With Absence of Rash.
Absence of rash is evaluated 24 hours preceding Week 1 and 7 days preceding Week 2, Week 4, Week 8 and Week 12. Only data at Week 2 reported here.
Measured: Week 2
Change From Baseline in CRP.
Change from baseline in CRP. Results at Week 2 reported here.
Measured: Week 2
Change From Baseline in Hemoglobin (Hb). Results at Week 2 Reported Here.
Change from baseline in Hemoglobin (Hb). Results at Week 2 reported here.
Measured: Week 2
Change From Baseline in Platelet Count.
Change from baseline in platelet count. Results at Week 2 reported here.
Measured: Week 2
Change From Baseline in Ferritin.
Change from baseline in ferritin. Results at Week 2 reported here.
Measured: Week 2
Change From Baseline in Patient/Parent Global Assessment of Disease Related Pain.
Assessed on a VAS from no pain (0 mm) to very severe pain (100 mm).
Measured: Week 2
Time to Study Drug Discontinuation for Any Reason.
Time to study drug discontinuation was analyzed using Kaplan-Meier curves. Number of patients with premature study drug discontinuation for any reason is reported here.
Measured: From Day 1 to Week12
Time to Study Drug Discontinuation Due to Lack of Efficacy or Progressive Disease.
Proportion of study drug discontinuation due to lack of efficacy or progressive disease was analyzed using Kaplan-Meier curves. Number of patients discontinuing study drug due to lack of efficacy or progressive disease is reported here.
Measured: From Day 1 to Week12
Proportion of Patients Who Have Initiated Tapering of Glucocorticoids.
Please note no patients were treated with any systemic glucocorticoids at randomization. Hence no results available
Measured: From Week 2 to Week12
Proportion of Patients That Have Decreased the Glucocorticoid Dose With at Least 50% From Baseline.
Please note no patients were treated with any systemic glucocorticoids at randomization. Hence no results available
Measured: From Week 2 to Week12
Percentage Decrease of the Glucocorticoid Dose From Baseline.
Please note no patients were treated with any systemic glucocorticoids at randomization. Hence no results available
Measured: From Day 1 to Week12
Proportion of Patients With at Least One Adverse Event.
All adverse events collected from start of study treatment up to 28 days after stopping study treatment.
Measured: From Day 1 to Week 16
Proportion of Patients With at Least One Serious Adverse Event Including Death.
Serious adverse events (SAEs) will be collected from informed consent up to 28 days after stopping study treatment.
Measured: From Informed consent to Week 16
Proportion of Patients With Macrophage Activation Syndrome (MAS).
Proportion of patients with Macrophage Activation Syndrome (MAS).
Measured: From Day 1 to Week 16
Proportion of Patients With Antidrug Antibodies (ADA) Against Anakinra.
Proportion of patients with antidrug antibodies (ADA) against anakinra.
Measured: Week 2
Proportion of Patients With Neutralizing Antibodies.
Confirmed ADA positive samples will be analyzed for the presence of neutralizing antibodies.
Measured: Week 2
Anakinra Serum Pre-dose Concentrations.
Week 2 reported here.
Measured: Week 2
Anakinra Serum Pharmacokinetic Parameters: Cmax,
PK parameters only available for 2 patients.
Measured: Week 12
Anakinra Serum Pharmacokinetic Parameters, Tmax and T½
PK parameters only available for 2 patients
Measured: Week 12
Anakinra Serum Pharmacokinetic Parameter: AUC 0-24 h
PK parameters only available for 2 patients
Measured: Week 12
Anakinra Serum Pharmacokinetic Parameter: CL/F
Pharmacokinetic parameters only available for 2 patients
Measured: Week 12
Anakinra Serum Pharmacokinetic Parameter: Vd/F
PK parameters only available for 2 patients
Measured: Week 12
Change From Baseline in JADAS27.
Juvenile Arthritis Disease Activity Score (JADAS) includes 4 measures: physician global assessment of disease activity, patient or parent global assessment of overall well-being, 27 active joint count, and CRP. The JADAS27 includes the 27 joints. JADAS27 is calculated as the sum of its four components, physician global assessment of disease activity converted to cm from the VAS (0=no activity, 10=maximum activity); patient global assessment of well-being converted to cm from the VAS (0=very well, 10=very poor); active joint count (0-27); and CRP. Prior to calculation CRP is truncated to a 0 - 10 scale according to the following formula: (CRP (mg/l) -10)/10. Before calculation, CRP values <10 mg/l are converted to 10 and CRP values >110 mg/l are converted to 110. The JADAS27 tool yields a global score of 0-57.
Only results from Week 2 reported here.
Measured: Week 2
Number of Days Off School or Work Due to Still's Disease.
Number of days off school or work due to Still's disease week 1-2.
Measured: Week 2
Proportion of Patients With Inactive Disease.
Inactive disease is a composite of the following parameters: no joints with active arthritis, no fever, no rash, no serositis, no splenomegaly, no generalized lymphadenopathy attributable to Still's disease, CRP level within normal limits, physician's global assessment of disease activity score below 10 mm on a 100 mm VAS and a documented morning stiffness ≤15 minutes.
Measured: Week 12
Change From Baseline in IL-6.
Only results from Week 2 reported here.
Measured: Week 2
Change From Baseline in IL-18.
Only results from Week 2 reported here
Measured: Week 2
Change From Baseline in Serum Calprotectin.
Change from baseline in serum calprotectin. Only results from Week 2 reported here
Measured: Week 2
Change From Baseline in Neopterin.
Only results from Week 2 reported here
Measured: Week 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2017
- Study start26 Sep 2017
- Primary completion13 Feb 2019
- Study completion23 May 2019
Why it stopped: Meeting enrolment target (81 pat) will not be feasible within reasonable time.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Still's Disease, Adult-OnsetStudies of the same condition, open and under way.
- More trials run by Swedish Orphan BiovitrumThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Swedish Orphan Biovitrum
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Sven Ohlman, MD PhD, Study director, Swedish Orphan Biovitrum
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03265132
- Sponsor's protocol ID
- Sobi.ANAKIN-301
- Acronym
- anaSTILLs
- Status last verified
- Jun 2021
- First submitted
- 25 Aug 2017
- Last updated
- 30 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled, Multicenter, Phase 3 Efficacy and Safety Study of 2 Dose Levels of Subcutaneous Anakinra (Kineret®) in Patients With Still's Disease (SJIA and AOSD)
- ClinicalTrials.gov ID
- NCT03265132
- Acronym / sponsor ID
- anaSTILLs / Sobi.ANAKIN-301
- Keywords
- Interleukin 1 receptor antagonist, IL-1 receptor antagonist, Kineret, anakinra, Adult-Onset Still's Disease, Systemic Juvenile Idiopathic Arthritis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Meeting enrolment target (81 pat) will not be feasible within reasonable time.
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Swedish Orphan BiovitrumIndustry (pharma, biotech, devices)
- Study start
- 26 Sep 2017 (actual)
- Primary completion
- 13 Feb 2019 (actual)
- Study completion
- 23 May 2019 (actual)
- First posted
- 29 Aug 2017 (actual)
- Results
- Posted 28 Apr 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this study is to demonstrate the efficacy and to evaluate the safety, pharmacokinetics (PK) and immunogenicity of anakinra in patients with newly diagnosed Still's disease, including SJIA (Systemic juvenile idiopathic arthritis) and AOSD (Adult-onset Still's disease).
Detailed description
The study consists of a 12-week, randomized, double-blind, placebo controlled period with two dose levels of anakinra and a 4-week safety follow-up after last dose of investigational medicinal product (IMP). The primary endpoint will be evaluated at Week 2. Sustained efficacy and time to study drug discontinuation will be evaluated during the full study period.
A screening visit is optional and may be done to identify patients that could be suitable for the study. During the study 6 visits and 2 telephone contacts are scheduled i.e., Day 1 (baseline visit), Day 4Tel, Week 1, Week 2, Week 4, Week 8, Week 12 and Week 16Tel (End of Study).
Patients will be randomly assigned to study drug, after they meet all of the inclusion criteria and none of the exclusion criteria. Patients will receive treatment for 12 weeks, either anakinra or placebo. Patients will be randomized to anakinra in a dose of either 2 or 4 mg/kg/day, with a maximum dose of 100 or 200 mg once daily, respectively. Patients will be randomized to placebo with corresponding volumes for each of the two anakinra dose levels.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| anakinra | Experimental | Biological: anakinra2 mg/kg/day (max 100 mg/day) or 4 mg/kg/day (max 200 mg/day) |
| Placebo | Placebo comparator | Drug: PlaceboCorresponding volume to anakinra 2 mg/kg/day or 4 mg/kg/day |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Signed informed consent.
- Male and female patients with a body weight ≥ 10 kg.
- Diagnosis of Still's disease.
- If currently on glucocorticoid treatment, a stable dose for at least 1 week prior to randomization.
- If currently on methotrexate treatment, a stable dose for at least 8 weeks prior to randomization.
Key exclusion criteria (25 listed)
- Diagnosis of Still's disease more than 6 months prior to randomization.
- Previous randomization into this study.
- Participation in another concurrent clinical interventional study within 30 days of randomization.
- Treatment with an investigational drug within 5 half-lives prior to randomization.
- Previous or current treatment with anakinra, canakinumab or any other IL-1 inhibitor.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| anakinraAlso: Kineretsub cutaneous injection | Biological | anakinra |
| Placebosub cutaneous injection | Drug | Placebo |
Primary outcome
Proportion of ACR30 Responders With Absence of Fever Attributable to the Disease During the 7 Days Preceding Week 2.
Time frame: Week 2
ACR30 response is defined as an improvement of ≥ 30% from baseline in at least 3 of any 6 variables listed below. Also no more than 1 of the 6 variables may worsen by >30% from baseline. (ACR: American College of Rheumatology) 1. Physician global assessment of disease activity - Assessed on a Visual Analogue Scale (VAS) from no disease activity (0 mm) to very severe disease activity (100 mm). 2. Patient/parent global assessment of overall well-being - Assessed on a VAS from very well (0 mm) to very poor (100 mm). 3. Number of joints with active arthritis. 4. Number of joints with limitation of motion. 5. Assessment of physical function - Patient Reported Outcome instruments : Childhood Health Assessment Questionnaire (CHAQ) /Stanford Health Assessment Questionnaire (SHAQ). 6. C-Reactive Protein (CRP) (mg/L).
49 secondary outcomes
Proportion of ACR30 Responders With Absence of Fever During 24 Hours Preceding Week 1.
Time frame: Week 1
Proportion of ACR50 Responders With Absence of Fever During 24 Hours Preceding Week 1.
Time frame: Week 1
Proportion of ACR70 Responders With Absence of Fever During 24 Hours Preceding Week 1.
Time frame: Week 1
Proportion of ACR90 Responders With Absence of Fever During 24 Hours Preceding Week 1.
Time frame: Week 1
Proportion of ACR50 Responders With Absence of Fever During 7 Days Preceding Week 2.
Time frame: Week 2
Proportion of ACR70 Responders With Absence of Fever During 7 Days Preceding Week 2.
Time frame: Week 2
Proportion of ACR90 Responders With Absence of Fever During 7 Days Preceding Week 2.
Time frame: Week 2
Proportion of Responders in Physician Global Assessment of Disease Activity.
Time frame: Week 2
Proportion of Responders in Patient/Parent Global Assessment of Overall Well-being.
Time frame: Week 2
Proportion of Responders in Number of Joints With Active Arthritis.
Time frame: Week 2
Proportion of Responders in Number of Joints With Limitation of Motion.
Time frame: Week 2
Proportion of Responders in Assessment of Physical Function (CHAQ/SHAQ).
Time frame: Week 2
Proportion of Responders in CRP (mg/L).
Time frame: Week 2
Proportion of Patients With Absence of Fever During the 7 Days Preceding Week 2.
Time frame: Week 2
Proportion of Patients With Absence of Fever During the 24 Hours Preceding Week 1.
Time frame: Week 1
Change From Baseline in Physician Global Assessment of Disease Activity at Week 1.
Time frame: Day 1 and Week 1
Change From Baseline in Patient/Parent Global Assessment of Overall Well-being at Week 1.
Time frame: Day 1 and Week 1
Change From Baseline in CRP.
Time frame: Day 1 and Week 1
Proportion of Patients With Sustained ACR30, ACR50, ACR70 and ACR90 Response.
Time frame: Week 12
Proportion of Patients With Sustained ACR30, ACR50, ACR70 and ACR90 Response in Relation to Glucocorticoid Tapering.
Time frame: Week 2, Week 4, Week 8 and Week 12
Proportion of Patients With Absence of Rash.
Time frame: Week 2
Change From Baseline in CRP.
Time frame: Week 2
Change From Baseline in Hemoglobin (Hb). Results at Week 2 Reported Here.
Time frame: Week 2
Change From Baseline in Platelet Count.
Time frame: Week 2
Change From Baseline in Ferritin.
Time frame: Week 2
Change From Baseline in Patient/Parent Global Assessment of Disease Related Pain.
Time frame: Week 2
Time to Study Drug Discontinuation for Any Reason.
Time frame: From Day 1 to Week12
Time to Study Drug Discontinuation Due to Lack of Efficacy or Progressive Disease.
Time frame: From Day 1 to Week12
Proportion of Patients Who Have Initiated Tapering of Glucocorticoids.
Time frame: From Week 2 to Week12
Proportion of Patients That Have Decreased the Glucocorticoid Dose With at Least 50% From Baseline.
Time frame: From Week 2 to Week12
Percentage Decrease of the Glucocorticoid Dose From Baseline.
Time frame: From Day 1 to Week12
Proportion of Patients With at Least One Adverse Event.
Time frame: From Day 1 to Week 16
Proportion of Patients With at Least One Serious Adverse Event Including Death.
Time frame: From Informed consent to Week 16
Proportion of Patients With Macrophage Activation Syndrome (MAS).
Time frame: From Day 1 to Week 16
Proportion of Patients With Antidrug Antibodies (ADA) Against Anakinra.
Time frame: Week 2
Proportion of Patients With Neutralizing Antibodies.
Time frame: Week 2
Anakinra Serum Pre-dose Concentrations.
Time frame: Week 2
Anakinra Serum Pharmacokinetic Parameters: Cmax,
Time frame: Week 12
Anakinra Serum Pharmacokinetic Parameters, Tmax and T½
Time frame: Week 12
Anakinra Serum Pharmacokinetic Parameter: AUC 0-24 h
Time frame: Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sven Ohlman, MD PhD study director
Swedish Orphan Biovitrum
39 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing anakinra in people with Still's Disease, Adult-Onset and Still's Disease, Juvenile-Onset, run by Swedish Orphan Biovitrum at 39 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 30 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 39 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Apr 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of ACR30 Responders With Absence of Fever Attributable to the Disease During the 7 Days Preceding Week 2. (time frame: Week 2). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jun 2021.