A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PRO-203 in Healthy Volunteers and Participants With Systemic Sclerosis

A Two-part, Phase 1, Randomized, Double-blind, Placebo-controlled, Single-ascending-dose Study in Healthy Adult Volunteers Followed by an Open-label, Single-ascending-dose With Priming Study in Participants With Systemic Sclerosis to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PRO-203

The purpose of this study is to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of PRO-203 in healthy volunteers and participants with systemic sclerosis.

Participants will be given PRO-203 under the skin (i.e., subcutaneously).

Study Overview

• Status: Recruiting
• Conditions: Scleroderma, Systemic; Healthy Volunteers; Scleroderma; Systemic Sclerosis (SSc)
• Intervention / Treatment: Drug: PRO-203; Other: Placebo

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) Up to 5 cohorts (with up to 2 additional optional cohorts) of approximately 5-10 healthy adults per cohort will be enrolled. Participants within each cohort will receive a single SC dose of PRO-203 or matching placebo.

Part 2 - Systemic Sclerosis (SSc) Up to 24 participants with SSc will be enrolled in 3 cohorts (with optional additional cohorts). Each cycle consists of a priming dose on Day 1 of Week 1 followed by a therapeutic dose on Day 1 of Week 2. 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.

• Study Type: Interventional
• Enrollment (Estimated): 74
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Sergio Rodriguez; Phone Number: (646) 597-6980; Email: info@proliumbio.com

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Recruiting
      • Nucleus Network
      • Contact: Sergio Rodriguez; Phone Number: 512-743-9737; Email: sr@proliumbio.com
• China
  • Nanjing, China
    • Not yet recruiting
    • Nanjing Drum Tower Hospital
    • Contact: Sergio Rodriguez; Phone Number: 512-743-9737; Email: sr@proliumbio.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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

• 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 Exclusion Criteria for Part 1

• Use of any prescription medication within 14 days and OTC medications, vitamins, herbal medications (e.g., St. John's wort), or cannabis, except for contraceptive medications and as needed (prn) acetaminophen/paracetamol (not exceeding 2 grams/day) within 7 days prior to administration of the study drug and throughout the study.

Additional Exclusion Criteria for Part 2

• Rheumatic autoimmune disease other than SSc.
• Positive anti-centromere antibodies.
• Pulmonary disease with FVC ≤ 45% of predicted, or DLCO ≤ 35% of predicted.
• Class 2 or higher pulmonary arterial hypertension or evidence of other moderately severe pulmonary disease.
• Renal crisis within 6 months prior to Screening.
• Prior treatment with cellular immunotherapy (eg, CAR-T) or gene therapy product directed at any target.
• Previous treatment with chlorambucil, bone marrow transplantation, or total lymphoid irradiation.
• Previous treatment with thalidomide, anti-thymocyte globulin, plasmapheresis, or extracorporeal photopheresis.
• Unable to washout current immunosuppressive therapy within 2 months
• Has received anti-CD19 or CD20 therapies, within 6 months prior to start of therapy
• Plan to receive live or live-attenuated vaccines within 8 weeks prior to first dose of study drug and during treatment until B cell reconstitution to 80% of baseline (inactive vaccines, such as the flu vaccine, are allowed)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: PRO-203; Healthy participants receive single ascending dose of PRO-203 across 5 sequential cohorts	Drug: PRO-203; PRO-203 administered as escalating single doses in healthy participants or as sequential multiple-dose regimens in participants with systemic sclerosis.
Placebo Comparator: Part 1: Placebo; Matching SC placebo administered to randomized Part 1 participants	Other: Placebo; Matching placebo comparator for Part 1 participants.
Experimental: Part 2: Multiple Doses of PRO-203; Participants with systemic sclerosis receive PRO-203 across a multiple dose regimen across 3 sequential cohorts, including optional retreatment in LTE.	Drug: PRO-203; PRO-203 administered as escalating single doses in healthy participants or as sequential multiple-dose regimens in participants with systemic sclerosis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-emergent adverse events (TEAEs)	TEAEs graded by type and frequency per NCI CTCAE v5.0. Applies to Part 1 (Healthy Volunteers) and Part 2 Main Study (Systemic Sclerosis).	From time of first dose through week 13.
Number of participants with treatment-emergent serious adverse events (TESAEs).	TESAEs graded by type and frequency per NCI CTCAE v5.0. Applies to Part 1 (Healthy Volunteers) and Part 2 Main Study (Systemic Sclerosis).	From time of first dose through Week 13
Number of participants with dose-limiting toxicities (DLTs)	DLT defined per protocol as any related TEAE of NCI CTCAE v5.0. Applies to Part 1 (Healthy Volunteers) and Part 2 Main Study (Systemic Sclerosis).	From time of first dose through Week 13.
Number of participants with clinically significant changes in clinical laboratory values	Clinical significance determined by investigator judgment per NCI CTCAE v5.0. Applies to Part 1 (Healthy Volunteers) and Part 2 Main Study (Systemic Sclerosis).	From time of first dose through Week 13
Number of participants with clinically significant changes in 12-lead ECG parameters	Standard 12-lead ECG parameters such as heart rate, PR interval, QRS duration, QT interval, and corrected QT interval (QTcF). Clinical significance determined by investigator judgment. Applies to Part 1 (Healthy Volunteers) and Part 2 Main Study (Systemic Sclerosis).	From time of first dose through Week 13
Number of participants with clinically significant changes in vital signs	Vital signs can include systolic and diastolic blood pressure, pulse rate, respiratory rate, and temperature. Clinical significance determined by investigator judgment. Applies to Part 1 (Healthy Volunteers) and Part 2 Main Study (Systemic Sclerosis).	From time of first dose through Week 13
Number of participants with TEAEs (Part 2 SSc, Long-term Extension)	Applies to Part 2 (Systemic Sclerosis) Long-term Extension (LTE). Includes TEAEs occurring during LTE. TEAEs graded by type and frequency per NCI CTCAE v5.0.	From time of first dose through Week 49
Number of participants with TESAEs (Part 2 SSc, Long-term Extension)	Applies to Part 2 (Systemic Sclerosis) Long-term Extension (LTE). Includes TESAEs occurring during LTE. TESAEs graded by type and frequency per NCI CTCAE v5.0.	From time of first dose through Week 49
Number of participants with clinically significant changes in clinical laboratory values or vital signs (Part 2 SSc, Long-term Extension)	Applies to Part 2 (Systemic Sclerosis) Long-term Extension (LTE). Clinical significance determined by investigator judgment per NCI CTCAE v5.0.	From time of first dose through Week 49

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Serum Concentration (Cmax) of PRO-203	Cmax derived from serum concentration-time data following single ascending dose (Part 1 HV) and single-cycle ascending dose (Part 2 SSc) administration.	From time of first dose through Week 13
Time to Maximum Serum Concentration (Tmax) of PRO-203	Tmax derived from serum concentration-time data following single ascending dose (Part 1 HV) and single-cycle ascending dose (Part 2 SSc) administration.	From time of first dose through Week 13
Area Under the Serum Concentration-Time Curve (AUC) of PRO-203	AUC derived from serum concentration-time data following single ascending dose (Part 1 HV) and single-cycle ascending dose (Part 2 SSc) administration.	From time of first dose through week 13
Systemic Clearance of PRO-203	Systemic clearance derived from serum concentration-time data following single ascending dose (Part 1 HV) and single-cycle ascending dose (Part 2 SSc) administration.	From time of first dose through week 13
Elimination Half-Life (t1/2) of PRO-203	Elimination half-life derived from serum concentration-time data following single ascending dose (Part 1 HV) and single-cycle ascending dose (Part 2 SSc) administration.	From time of first dose through Week 13
Change from Baseline in Peripheral Blood B Cell Counts	Pharmacodynamic effects of single ascending doses of PRO-203 on B cell (CD3-CD19+) counts in Part 1 (Healthy Volunteers) and Part 2 Main Study (Systemic Sclerosis).	From time of first dose through Week 13
Change from Baseline in Peripheral Blood T Cell Counts	Pharmacodynamic effects of single ascending doses of PRO-203 on T cell (CD3+) counts in Part 1 (Healthy Volunteers) and Part 2 Main Study (Systemic Sclerosis).	From time of first dose through Week 13
Incidence of Anti-Drug Antibodies (ADA) to PRO-203	Immunogenicity of PRO-203 assessed by incidence of anti-drug antibodies (ADA) in Part 1 (Healthy Volunteers) and Part 2 Main Study (Systemic Sclerosis).	From time of first dose through Week 13
Maximum Serum Concentration (Cmax) of PRO-203 Post-Retreatment	Cmax derived from serum concentration-time data following retreatment cycle(s) in eligible participants.	From time of first dose through Week 49
Time to Maximum Serum Concentration (Tmax) of PRO-203 Post-Retreatment	Tmax derived from serum concentration-time data following retreatment cycle(s) in eligible participants.	From time of first dose through Week 49
Area Under the Serum Concentration-Time Curve (AUC) of PRO-203 Post-Retreatment	AUC derived from serum concentration-time data following retreatment cycle(s) in eligible participants.	From time of first dose through Week 49
Systemic Clearance of PRO-203 Post-Retreatment	Systemic clearance derived from serum concentration-time data following retreatment cycle(s) in eligible participants.	From time of first dose through Week 49
Elimination Half-Life (t1/2) of PRO-203 Post-Retreatment	Elimination half-life derived from serum concentration-time data following retreatment cycle(s) in eligible participants.	From time of first dose through Week 49
Change from Baseline in Peripheral Blood B Cell Counts	Long-term pharmacodynamic profile of B cell (CD3-CD19+) counts in Part 2 (Systemic Sclerosis) Long-term Extension (LTE)	From time of first dose through Week 49
Change from Baseline in Peripheral Blood T Cell Counts	Long-term pharmacodynamic profile of T cell (CD3+) counts in Part 2 (Systemic Sclerosis) Long-term Extension (LTE)	From time of first dose through Week 49
Incidence of Anti-Drug Antibodies (ADA) to PRO-203	Immunogenicity of PRO-203 assessed by incidence of anti-drug antibodies (ADA) in Part 2 (Systemic Sclerosis) Long-term Extension (LTE).	From time of first dose through Week 49

Collaborators and Investigators

• Sponsor: Prolium Bioscience, Inc
• Investigators: Study Director: Salim Mujais, Prolium Bioscience, Inc

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: December 10, 2025
• First Submitted That Met QC Criteria: June 7, 2026
• First Posted (Actual): June 11, 2026

Study Record Updates

• Last Update Posted (Actual): June 11, 2026
• Last Update Submitted That Met QC Criteria: June 7, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: B cell depletion; Scleroderma; Systemic sclerosis; SSc
• Additional Relevant MeSH Terms: Connective Tissue Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Scleroderma, Systemic; Scleroderma, Diffuse
• Other Study ID Numbers: PRO-203-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No