Healthy Volunteers, Scleroderma, Scleroderma, Systemic, Systemic Sclerosis (SSc)
Conditions
Keywords
Systemic sclerosis, SSc, Scleroderma, B cell depletion
Brief summary
A two-part study of PRO-203 administered subcutaneously in healthy adult volunteers and participants with Systemic Sclerosis (SSc).
Detailed description
This two-part study is designed to characterize the first-in-human safety, tolerability, PK, and PD profile of PRO-203 across ascending dose levels. Part 1 - Healthy Volunteers (HV) Part 1 enrollment is complete and has enrolled 20 healthy volunteers across 3 cohorts. Participants within each cohort received a single SC dose of PRO-203 or matching placebo. Part 1 has completed enrollment. Part 2 - Systemic Sclerosis (SSc) Up to 24 participants with SSc will be enrolled in multiple cohorts (with optional additional cohorts) Participants within each cohort will receive a single SC cycle of PRO-203. Part 2 includes a Main Study and an optional Long-term Extension (LTE). In the LTE, eligible participants may receive retreatment if they meet retreatment criteria. Total study duration per participant is up to 53 weeks.
Interventions
DRUGPRO-203
PRO-203 administered as escalating single dose in healthy participants or as a single cycle in participants with systemic sclerosis.
OTHERPlacebo
Matching placebo comparator for Part 1 participants.
Sponsors
Prolium Bioscience, Inc
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Double (Participant, Investigator) - Part 1 only; Open Label - Part 2
Intervention model description
Dose escalation
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria (All Participants) * Is male or female, age 18 to 65 years, inclusive, at Screening. * Able to provide Informed Consent. * Absolute B cell count \> 25 cells/uL. Additional Inclusion for Part 1 (Closed to Enrollment) * In good general health, determined by no clinically significant findings in the of the investigator from medical history, physical examination, 12-lead ECG, clinical laboratory findings, and vital signs at Screening and Day -1 (participants with Gilbert's disease with associated abnormalities of liver function tests are eligible for enrollment). * Up to date vaccination status per local guidelines (including but not limited to influenza vaccine, COVID booster and hepatitis B vaccine). Additional Inclusion for Part 2 * Fulfill 2013 ACR/ EULAR criteria for classification of SSc with a total score of ≥ 9. * Active disease defined as at least two of the following at screening: * Disease duration ≤ 2 years (since onset of first-non-Raynaud-symptom), or * Elevated acute phase reactant levels (CRP ≥ 6 mg/L, erythrocytes sedimentation rate \[ESR\] ≥ 28 mm/1h, or platelet count ≥ 330,000/µL), or * Baseline mRSS ≥10 with evidence of progression, defined as mRSS increase at least 3 units, or involvement of 1 new body area and mRSS increase at least 2 units, or involvement of 2 new body areas (each within the previous 6 months), or * ≥ 1 tendon friction rub, or * Elevation of CK or aldolase \> 2 × the upper limit of normal (ULN) consistent with SSc-related myopathy, or * Progressive fibrosing interstitial lung disease (ILD) as defined by at least one of the following criteria at any time within the prior 2 years: 1. relative decline in forced vital capacity (FVC) % predicted ≥ 10%, or 2. relative decline in FVC % predicted ≥ 5% to \<10% and worsened respiratory symptoms, or 3. relative decline in FVC % predicted ≥ 5% to \<10% and increased extent of fibrosis on high-resolution computed tomography (HRCT), or 4. worsened respiratory symptoms and increased extent of fibrosis on HRCT * Intolerant or refractory to at least 1 line of standard therapy, including methotrexate, azathioprine, IVIG, mycophenolic acid derivatives, cyclophosphamide, TNF-inhibitors, rituximab, or tocilizumab. Key
Exclusion criteria
(All Participants) * Any clinically significant underlying illness in the opinion of the investigator. * Active infection within 4 weeks prior to screening. Participants receiving IV antibiotics or having received IV antibiotics within 14 days prior to enrollment are excluded. * Positive QuantiFERON-Gold TB test at screening. * Plan to receive live, attenuated vaccine after signing ICF (inactive vaccines, such as the flu vaccine, are allowed). * Evidence of malignant disease or malignancies diagnosed within the previous 5 years (except for treated local basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that had been excised and cured). * Currently enrolled in another investigational device or drug study, or less than 30 days or 5 half-lives of the prior investigational agent (whichever is longer) have passed since ending another investigational device or drug study or plans to enroll in another investigational device or drug study during the course of this study. * Social smokers e.g. up to 10 cigarettes per week (or equivalent amounts of nicotine containing products) and willing to abstain during inpatient stay, are allowed Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events and Laboratory Abnormalities [Safety and Tolerability] | 13 weeks (Part 1) / 49 weeks (Part 2) | Incidence and severity of treatment-emergent adverse events, serious adverse events, and dose-limiting toxicities, including changes in clinical laboratory values, ECGs, and vital signs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics of PRO-203 | 13 weeks (Part 1) / 49 weeks (Part 2) | Serum drug levels of PRO-203 over time |
| Pharmacodynamic-related biomarkers of PRO-203 | 13 weeks (Part 1) / 49 weeks (Part 2) | Peripheral blood B lymphocyte levels over time |
| Immunogenicity of PRO-203 | 13 weeks (Part 1) / 49 weeks (Part 2) | Level of anti-drug antibodies |
Countries
Australia, China, Mexico, South Korea
Contacts
CONTACTSergio Rodriguez
STUDY_DIRECTORSalim Mujais
Prolium Bioscience, Inc
Outcome results
None listed