Clinical Trials

Inclusion Criteria - MAD Stage:

• Signed Informed Consent Form.
• Age 18-75 years at time of signing Informed Consent Form.
• Weight of 45-150 kg at screening.
• Ability to comply with the study protocol.
• Diagnosis of SSc, as defined by 2013 ACR/EULAR criteria.
• 10 years disease duration from first non-Raynaud’s sympto.
• For patients with dcSSc, ≥ 15 mRSS units at screening and baseline and with skin available for biopsy preferably on proximal forearms having mRSS ≥ 2 at the biopsy location (alternative sites with relevant mRSS scores may be biopsied).
• For patients with lcSSc, ≥ 9 mRSS units at screening and baseline and with lesional skin available for biopsy preferably on proximal forearms having mRSS ≥ 2 at the biopsy location (alternative sites with relevant mRSS scores may be biopsied).

Inclusion Criteria - Open-Label Safety Extension Stage:

• Signed OSE Informed Consent Form.
• No clinically significant change in eligibility status The urine drug screen and viral serology need not be repeated unless clinically indicated.
• Completion of the MAD Day 113 (first 5 dose-escalation patients per cohort) or Day 85 (all other patients without withdrawal from treatment) and ability to roll over into the OSE within 5 days.
• Patients on stable doses of MMF, MTX, HCQ, AZA, SSZ, TCZ, and/or oral corticosteroids should not have the prospective intent to discontinue or change the dose over the 52-week duration of the OSE; and patients not already on a stable dose of any of the aforementioned therapies should not have a prospective intent to initiate treatment during the course of the OSE treatment period.

Exclusion Criteria:

• Active rheumatic autoimmune disease other than SSc requiring treatment with disease-modifying therapy, including, but not limited to, RA, systemic lupus erythematosus, mixed connective tissue disorder, polymyositis, dermatomyositis, eosinophilic fasciitis, primary Sjögren syndrome, eosinophilic myalgia syndrome, and pneumonitis, as determined by the investigator.
• Pulmonary disease with FVC.
• 50% of predicted.
• Known pulmonary arterial hypertension (PAH; WHO Class II or higher), as determined by the investigator.
• Recent history (within 3 months for any of the following) of root canal, unresolved dental infection, poor dentition, Grade ≥ 2 gingival or periodontal disorders (e.g., hyperplasia, inflammation, bleeding), and/or dental implant placement.
• History or clinical manifestations of significant metabolic, hepatic, renal, pulmonary, cardiovascular, hematologic, gastrointestinal, urologic, neurologic, or psychiatric disorders that may impact safe participation for the duration of the trial, as determined by the investigator.
• History of uncontrolled hypertension.
• History of malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer.
• History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies.
• History of solid organ or stem-cell transplantation.
• Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study.
• History or presence of an abnormal ECG that is deemed clinically significant by the investigator, including complete left bundle branch block, second- or third-degree atrioventricular heart block, or evidence of prior (within last 12 months) myocardial infarction.
• History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease (e.g., severe left ventricular systolic dysfunction, left ventricular hypertrophy), coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), or family history of sudden unexplained death or long QT syndrome.
• History of aortic disease or any clinically significant abnormality on the screening echo, including evidence of aortic disease (e.g., dissection, aneurysm), or LVEF 50% or below the LLN.
• History of stroke (ischemic or hemorrhagic) or transient ischemic attack or other significant vascular disease (e.g., recent peripheral arterial thrombosis) within 6 months prior to initiation of study treatment.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 10/5/23. Questions regarding updates should be directed to the study team contact.