Eligibility Details:
Main Inclusion Criteria:
1. Capable of giving written informed consent, which includes compliance with study
requirements and restrictions listed in the consent form.
2. Age requirements:
- Cohorts 1 through 4 (healthy): Male or female age ≥ 18 years and ≤ 50 years.
- Cohort 5 (AS): Male or female age ≥ 18 years and ≤ 75 years.
3. Females must agree to use a highly effective birth control method (<1% failure rate
per year) throughout the study, reproductive status of non-childbearing based on
medical history, or is postmenopausal:
- Non-childbearing potential defined as pre-menopausal female with medical history
of bilateral tubal ligation, bilateral oophorectomy (removal of the ovaries) or
hysterectomy; hysteroscopic sterilization,
- Postmenopausal defined as 12 months of spontaneous amenorrhea; with follicle
stimulating hormone (FSH) confirmation.
- Woman of Childbearing potential (WCBP) who is already using an established method
of highly effective contraception or agrees to use one of the allowed BC methods
for at least 28 days prior to the start of dosing (as determined by the
Investigator Brochure or Investigator or designee) to sufficiently minimize the
risk of pregnancy throughout study participation (until completion their study
follow-up visit).
4. Males who are sexually active must agree to use one of the allowed birth control
methods. Male subjects must also agree to sufficiently minimize the risk of pregnancy
throughout study participation (until completion their follow-up visit).
5. Body Mass Index (BMI):
- Cohorts 1-4 (healthy): BMI 18.5 to 31 kg/m2 at Screening
- Cohort 5 (AS): BMI 18 to 33 kg/m2 at Screening
Additional Inclusion Criteria for Cohort 5 (AS) only:
6. AS diagnosis fulfilling the Modified New York criteria for AS.
7. Active AS, as defined by the Bath Ankylosing Spondylitis Disease Activity Index
(BASDAI) ≥ 4 despite NSAID, corticosteroid or DMARD therapy.
8. BASDAI, item 2, spinal pain score ≥ 4 (out of 10).
9. AS diagnosis confirmed by Sacroiliac (SI) imaging within the last 2 years (confirmed
by central reader during Screening).
10. Does not have a history of complete spinal ankylosis.
11. CRP > ULN at Screening.
12. Two prior failures to NSAID therapy (sub-optimal clinical response following four
weeks at maximum tolerated dose) or intolerance to NSAID therapy.
Main Exclusion Criteria:
An individual will NOT be eligible for inclusion in this study if any of the following
criteria apply.
1. Clinically significant illness which required medical treatment within 8 weeks or a
clinically significant infection within 4 weeks prior to Screening.
2. Disease diagnosis that may influence the outcome of the study; such as psychiatric
disorders or disorders of the gastrointestinal tract, liver, kidney, respiratory
system, endocrine system, hematological system, neurological system, cardiovascular
system within 4 weeks prior to randomization, or individuals who have preexisting
metabolic congenital abnormality(ies).
3. Positive Quantiferon test.
4. Use of prescription and non-prescription drugs:
- Cohorts 1 through 4 (healthy): Use of prescription or non-prescription drugs,
including vitamins, herbal and dietary supplements within 14 days or 5 half-lives
(whichever is longer) prior to the first dose of study treatment, unless in the
opinion of an Investigator and Medical Monitor the medication will not interfere
with the study procedures or compromise subject safety or permitted under Section
5.10.1.
- Cohort 5 (AS):
- Current or prior treatment regimen that includes a biologic therapy (e.g.,
anti-TNF-alpha, anti-IL-17A, anti-IL-6, or anti-IL-12/23)
- Use of parenteral and/or intra-articular steroids or immunosuppressants within 6
weeks prior to the first dose of study treatment.
Oral steroids are permitted if the dosage is ≤10 mg/day prednisone (or equivalent) and
is stable for a minimum of 4 weeks before the first dose of study treatment and
remains unchanged throughout the study.
Also note:
Oral NSAID treatment is permitted if the dosage is stable for a minimum of 2 weeks
before the first dose of study treatment and remains unchanged throughout the study.
Oral sulfasalazine treatment is permitted if the dosage is ≤ 3 g/d (max) and is stable
for a minimum of 4 weeks before the first dose of study treatment and remains
unchanged throughout the study.
Oral methotrexate use is permitted if used for a minimum of 3 months, the dosage is ≤
20 mg/week, and is the dose stable for a minimum of 4 weeks (including dosage of
concomitant folate) before the first dose of study treatment and remains unchanged
throughout the study.
Subcutaneous methotrexate use is permitted if the dosage is ≤ 20 mg/week and is stable
for a minimum of 4 weeks (including dosage of concomitant folate) before the first
dose of study treatment and remains unchanged throughout the study.
5. Individual who received an investigational product (including placebo) 30 days prior
to the start of dosing (5 half-lives or twice the duration of the biological effect of
the investigational product), whichever is longer.
6. Weight loss or gain of >10% between screening and up to the start of dosing.
7. Hemoglobin level ≤ 12 g/dL at Screening.
8. Positive result for HIV (HIV-1/HIV-2 Antibodies), HBsAg or HCVAb screening tests.
9. Known or suspected history of drug abuse (amphetamines, barbiturates, cannabinoids,
cocaine, opiates and phencyclidine) or alcohol misuse* within 6 months prior to
Screening, or a positive urine drug test and/or alcohol breathalyzer test at Screening
or baseline.
common.study.methods.has-drugs-yes
common.study.methods.is-healthy-no
