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

Exclusion Criteria19

• 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
• 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.
• 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)