A Phase 1/2 Study of PRO-203 in Healthy Volunteers and Participants With Systemic Sclerosis.

Official title

A Two-part, Phase 1/2, Randomized, Double-blind, Placebo-controlled, Single-ascending-dose Study of PRO-203 in Healthy Adult Volunteers Followed by an Open-label, Single-ascending-dose With Priming Study of PRO-203 in Participants With Systemic Sclerosis

Overview

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

• Drug PRO-203
  PRO-203 administered as escalating single dose in healthy participants or as a single cycle in participants with systemic sclerosis.
• Other Placebo
  Matching placebo comparator for Part 1 participants.

Primary outcome measures

• Incidence of Adverse Events and Laboratory Abnormalities [Safety and Tolerability] [Time frame: 13 weeks (Part 1) / 49 weeks (Part 2)]

Secondary outcome measures (3)

• Pharmacokinetics of PRO-203 [Time frame: 13 weeks (Part 1) / 49 weeks (Part 2)]
• Pharmacodynamic-related biomarkers of PRO-203 [Time frame: 13 weeks (Part 1) / 49 weeks (Part 2)]
• Immunogenicity of PRO-203 [Time frame: 13 weeks (Part 1) / 49 weeks (Part 2)]

Eligibility 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:

• relative decline in forced vital capacity (FVC) % predicted ≥ 10%, or
• relative decline in FVC % predicted ≥ 5% to <10% and worsened respiratory symptoms, or
• relative decline in FVC % predicted ≥ 5% to <10% and increased extent of fibrosis on high-resolution computed tomography (HRCT), or
• 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 (Closed to Enrollment)

• 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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Triple blind

Primary purpose

Treatment

Study locations

China · 2 centers

• Peking University Third Hospital — Beijing
• Nanjing Drum Tower Hospital — Nanjing

Australia · 1 center

• Nucleus Network — Melbourne

Identifiers

NCT: NCT07641634 · PRO-203-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗