| Eligibility |
Inclusion Criteria:
1. Subject is 18 to 75 years of age (inclusive) at the time of consent. The date of
signature of the informed consent is defined as the beginning of the Screening Period.
This inclusion criterion will only be assessed at the Screening Visit (Visit 1).
2. Subject has been diagnosed with AOSD based on classification criteria (according to
Yamaguchi et al, 1992) defined as having 5 or more of the following criteria, 2 of
which are major:
a. Major Criteria i. Fever >39°C, lasting 1 week or longer ii. Arthralgia or
arthritis, lasting 2 weeks or longer iii. Typical rash iv. Leukocytes >10,000 mm3 with
>80% polymorphonuclear cells b. Minor Criteria i. Sore throat ii. Recent development
of significant lymphadenopathy iii. Hepatomegaly or splenomegaly iv. Abnormal liver
function tests v. Negative tests for antinuclear antibody and rheumatoid factor
3. Subject has reported a recurring fever >38°C, consistent with active disease, within
the last 5 days of the Screening and Baseline Visits.
4. If undergoing treatment with non-steroidal anti-inflammatory drugs (NSAID), subject is
on a stable dose for at least 48 hours prior to the Baseline Visit (Visit 2).
5. If undergoing treatment with glucocorticoids, subject is on a stable dose for at least
48 hours prior to the Baseline Visit (Visit 2).
6. If undergoing treatment with conventional disease-modifying anti-rheumatic drugs
(DMARDs), subject is on a stable dose for at least 4 weeks prior to the Baseline Visit
(Visit 2).
7. For subjects who have received treatment with biological DMARDs, subject has the
required washout (normalization) period prior to the Baseline Visit (Visit 2).
The washout (normalization) period for biological DMARDs is as follows:
1. Anakinra - 1 week
2. Etanercept, rilonacept - 4 weeks
3. Adalimumab, certolizumab, infliximab, golimumab, abatacept, tocilizumab and
canakinumab - 8 weeks
4. Rituximab - 36 weeks
8. Non-pregnant female subjects of childbearing potential who are heterosexually active
and non-sterile male subjects with female sexual partners of childbearing potential
agree to use a highly effective method of contraception during treatment and for 25
weeks following the last dose of investigational product. A highly effective method of
birth control is defined as one that results in a low failure rate (ie, <1% per year)
when used consistently and correctly, such as
oral/injectable/inserted/implanted/transdermal contraceptives, intrauterine
hormone-releasing system or intrauterine device (IUD), or sexual abstinence.
Contraception is not required where at least 6 weeks has passed since sterilization,
defined as females having undergone one of the following surgeries: hysterectomy,
bilateral tubal ligation or occlusion, bilateral oophorectomy, or bilateral
salpingectomy; and males who are vasectomized. Contraception is also not required
where females are postmenopausal (defined as 12 consecutive months of spontaneous
amenorrhea and age =51 years). Females of reproductive potential must have a negative
pregnancy test as part of the screening/baseline assessment.
9. Subject has provided written informed consent for this study.
10. Subject is willing and able to comply with the protocol.
Exclusion Criteria:
1. Subject is, in the opinion of the investigator, mentally or legally incapacitated, or
has significant emotional problems at the time of the Screening Visit (Visit 1) that
could interfere with the subject's participation or cooperation with the conduct of
study evaluations
2. Subject has a chronic severe or uncontrolled medical disorder that might confound the
results of safety assessments conducted in the study in the opinion of the
Investigator or Medical Monitor.
3. Subject has another serious chronic-inflammatory disease.
4. Subject has a relevant, active infection or another disease, which entails a tendency
towards infection.
5. Subject has active macrophage activation syndrome.
6. Subject has a history of unresolved latent tuberculosis.
7. Subject has the following abnormal values:
1. Serum creatinine concentration >1.5 mg/dl.
2. Hemoglobin = 10 g/dl, neutrophils =1,500/µl and/or thrombocytes =75,000/µl.
8. Subject has a history of neoplasia with the exception of a curatively treated
non-melanoma skin tumor or carcinoma of the cervix treated in situ without any
indication of recurrence within the last 10 years.
9. Subject has received a vaccination with a live vaccine within 12 weeks prior to the
Baseline Visit (Visit 2).
10. Subject has used an investigational product or been enrolled in a clinical study
including vaccines within 30 days of the Screening Visit (Visit 1).
11. Subject has known or suspected intolerance or hypersensitivity to the investigational
product(s), closely related compounds, or any ingredients of the investigational
product.
12. Subject is pregnant or is breastfeeding and will not abstain from breastfeeding during
participation in the study and for 25 weeks post last dose of investigational product.
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