Atopic Dermatitis (AD), Autoimmune Diseases, Cutaneous Lupus Erythematosus (CLE), Psoriasis (PsO), Psoriatic Arthritis (PsA), Rheumatoid Arthritis (RA)
Conditions
Keywords
Autoimmune, Immune-mediated, S-4321, Seismic Therapeutic, Rheumatoid Arthritis, Atopic Dermatitis (AD), Psoriasis (PsO), Psoriatic Arthritis (PsA), Cutaneous Lupus Erythematosus (CLE), Cutaneous Lupus
Brief summary
This is a multi-center, open-label Ph 1b basket study to assess safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, biomarker response, and preliminary efficacy of multiple doses of S-4321 in adults with autoimmune or immune-mediated disease including rheumatoid arthritis (RA), psoriatic arthritis (PsA), psoriasis (PsO), cutaneous lupus erythematosus (CLE) with or without systemic manifestations, or atopic dermatitis (AD).
Interventions
DRUGS-4321
Multiple doses of S-4321 via subcutaneous administration
Sponsors
Seismic Therapeutic AU Pty Ltd
Avance Clinical Pty Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
All Participants Major Inclusion Criteria: 1. Adult males and females, 18 to 75 years of age (inclusive) 2. Body mass index (BMI) ≥18.0 and \<40.0 kg/m2 with a minimum body weight of 45 kg 3. Use of adequate contraception for both males and females. Female volunteers must be of nonchildbearing potential or if of childbearing potential, must have a negative pregnancy test. All Participants Major
Exclusion criteria
1. Have received a PD-1 agonist, immune checkpoint agonist, immune checkpoint inhibitor, anti-CD19 or anti-CD20 agents, cell therapy, B cell modulating agents, alkylating agents, or any other immune cell depleting therapy. 2. Have received azathioprine, cyclosporine, mycophenolate mofetil, or tacrolimus within 4 weeks 3. Unable or unwilling to discontinue a prohibited medication 4. Presence of clinically relevant immunosuppression 5. Current infection or history of severe infection 6. Any history of malignant disease, with some exceptions Major inclusion/exclusion for each autoimmune or immune-mediated disease: For RA: 1. Confirmed diagnosis of moderate to severe active RA by the American College of Rheumatology (ACR) 2010/European League Against Rheumatism (EULAR) criteria for at least 3 months prior to the Screening 1 visit, and: 1. ≥6 swollen joint count based on 66 joint count 2. ≥6 tender joint count based on 68 joint count 3. Seropositive for RF and/or ACPA 4. Elevated hsCRP ≥1.2 times greater than the ULN 5. Does not have Class IV RA according to ACR revised criteria 2. Inadequate response to, or loss of response, or intolerance to: 1. \>1 conventional synthetic DMARD after 3 months of therapy OR 2. \>1 biologic DMARD/targeted synthetic DMARD after 3 months of therapy 3. Has not failed 3 or more bDMARDs and/or tsDMARDs For PsA: 1. Confirmed diagnosis of adult-onset PsA classified by the Classification Criteria for Psoriatic Arthritis (CASPAR) for at least 3 months prior to the Screening 1 visit, with all of the following: 1. Active PsO defined by at least 1 psoriasis lesion 2. Active disease defined by \>3 swollen joints and \>3 tender joints using the 76/78 swollen and tender joint count 2. Received standard doses of NSAIDs for \>4 weeks or csDMARDs for \>3 months and has been on a stable dose for \>8 weeks, or participant has intolerance to NSAIDs or DMARDs 3. Participants may be TNF inhibitor therapy naïve or may have received 1 prior TNF inhibitor 4. Has not had inadequate response or intolerance to 2 or more bDMARDs or csDMARDs For PsO: 1. Confirmed diagnosis of moderate to severe plaque PsO for at least 6 months, with all of the following: 1. Psoriasis Area and Severity Index (PASI) \>12 points 2. Static Physician's Global Assessment (sPGA) \>3 points 3. Body surface area (BSA) of PsO involvement \>10% 2. Cannot have a clinically significant flare within 12 weeks 3. Does not have history of erythrodermic psoriasis, generalized or localized pustular psoriasis, predominantly guttate psoriasis, or medication-induced or medication-exacerbated psoriasis 4. Has not had inadequate response to more than 2 prior bDMARDs For CLE (with or without systemic manifestations): 1. Histologically confirmed diagnosis of CLE with or without systemic manifestations for at least 6 months 2. Has active skin manifestations as measured by CLASI-A \>10 or CLASI-A \>8, if there is no alopecia or mucous membrane lesions 3. Participant must have an active CLE lesion despite an adequate trial of antimalarial treatment for at least 6 months. 4. Cannot have active lupus nephritis or moderate-to-severe or chronic kidney disease with eGFR \<45 mL/min/1.73m2 5. Cannot have active neuropsychiatric SLE For AD: 1. Confirmed diagnosis of AD as defined by the American Academy of Dermatology: Guidelines of Care for the Management of Atopic Dermatitis for at least 12 months 1. Eczema Area and Severity Index (EASI) \>16 2. Validated Investigator Global Assessment (vIGA-AD) \>3 3. BSA of AD involvement \>10% 4. PP-NRS) \>4 (average of daily scores) during the 7 days prior to dosing 2. Inadequate response to existing topical medications within 6 months or has a history of intolerance to topical therapy as defined by at least 1 of the following: 1. Inability to achieve good disease control after use TCS for at least 4 weeks 2. Documented history of clinically significant AEs with the use of TCS 3. Failed systemic therapies intended to treat AD within 6 months Additional inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of treatment-emergent adverse events (TEAEs) | Through Week 31 |
| Incidence of serious adverse events (SAEs) | Through Week 31 |
Secondary
| Measure | Time frame |
|---|---|
| Serum concentration of S-4321 | Through Week 28 |
| Change from baseline in percent Receptor Occupancy (RO) | Through Week 28 |
| Change from baseline of soluble PD-1 (sPD-1) | Through Week 28 |
| Incidence of anti-drug antibodies (ADAs) | Through Week 28 |
Countries
Australia
Contacts
CONTACTSeismic Contact
PRINCIPAL_INVESTIGATORJennifer Martin, MD
Novatrials
Outcome results
None listed