Study of S-4321 in Participants With an Autoimmune or Immune-mediated Disease

Официальное название

Phase 1b, Open-Label, Exploratory Biomarker Basket Study of S-4321 in Participants With an Autoimmune or Immune-Mediated Disease

Обзор

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).

Вмешательства

• Препарат S-4321
  Multiple doses of S-4321 via subcutaneous administration

Первичные конечные точки

• Incidence of treatment-emergent adverse events (TEAEs) [Срок оценки: Through Week 31]
• Incidence of serious adverse events (SAEs) [Срок оценки: Through Week 31]

Вторичные конечные точки (4)

• Serum concentration of S-4321 [Срок оценки: Through Week 28]
• Change from baseline in percent Receptor Occupancy (RO) [Срок оценки: Through Week 28]
• Change from baseline of soluble PD-1 (sPD-1) [Срок оценки: Through Week 28]
• Incidence of anti-drug antibodies (ADAs) [Срок оценки: Through Week 28]

Критерии участия

All Participants Major Inclusion Criteria:

• Adult males and females, 18 to 75 years of age (inclusive)
• Body mass index (BMI) ≥18.0 and <40.0 kg/m2 with a minimum body weight of 45 kg
• 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:

• 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.
• Have received azathioprine, cyclosporine, mycophenolate mofetil, or tacrolimus within 4 weeks
• Unable or unwilling to discontinue a prohibited medication
• Presence of clinically relevant immunosuppression
• Current infection or history of severe infection
• Any history of malignant disease, with some exceptions

Major inclusion/exclusion for each autoimmune or immune-mediated disease:

For RA:

• 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:

• ≥6 swollen joint count based on 66 joint count
• ≥6 tender joint count based on 68 joint count
• Seropositive for RF and/or ACPA
• Elevated hsCRP ≥1.2 times greater than the ULN
• Does not have Class IV RA according to ACR revised criteria
• Inadequate response to, or loss of response, or intolerance to:

• >1 conventional synthetic DMARD after 3 months of therapy OR
• >1 biologic DMARD/targeted synthetic DMARD after 3 months of therapy
• Has not failed 3 or more bDMARDs and/or tsDMARDs

For PsA:

• 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:

• Active PsO defined by at least 1 psoriasis lesion
• Active disease defined by >3 swollen joints and >3 tender joints using the 76/78 swollen and tender joint count
• 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
• Participants may be TNF inhibitor therapy naïve or may have received 1 prior TNF inhibitor
• Has not had inadequate response or intolerance to 2 or more bDMARDs or csDMARDs

For PsO:

• Confirmed diagnosis of moderate to severe plaque PsO for at least 6 months, with all of the following:

• Psoriasis Area and Severity Index (PASI) >12 points
• Static Physician's Global Assessment (sPGA) >3 points
• Body surface area (BSA) of PsO involvement >10%
• Cannot have a clinically significant flare within 12 weeks
• Does not have history of erythrodermic psoriasis, generalized or localized pustular psoriasis, predominantly guttate psoriasis, or medication-induced or medication-exacerbated psoriasis
• Has not had inadequate response to more than 2 prior bDMARDs

For CLE (with or without systemic manifestations):

• Histologically confirmed diagnosis of CLE with or without systemic manifestations for at least 6 months
• Has active skin manifestations as measured by CLASI-A >10 or CLASI-A >8, if there is no alopecia or mucous membrane lesions
• Participant must have an active CLE lesion despite an adequate trial of antimalarial treatment for at least 6 months.
• Cannot have active lupus nephritis or moderate-to-severe or chronic kidney disease with eGFR <45 mL/min/1.73m2
• Cannot have active neuropsychiatric SLE

For AD:

• 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

• Eczema Area and Severity Index (EASI) >16
• Validated Investigator Global Assessment (vIGA-AD) >3
• BSA of AD involvement >10%
• PP-NRS) >4 (average of daily scores) during the 7 days prior to dosing
• 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:

• Inability to achieve good disease control after use TCS for at least 4 weeks
• Documented history of clinically significant AEs with the use of TCS
• Failed systemic therapies intended to treat AD within 6 months

Additional inclusion/exclusion criteria will apply.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Австралия · 2 центра

• Novatrials — Charlestown
• University of the Sunshine Coast Clinical Trials, Birtinya — Birtinya

Идентификаторы

NCT: NCT07455578 · S-4321-102

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗