A Study of MK-2225 / ACE-1334 in Participants With Systemic Sclerosis With and Without Interstitial Lung Disease (MK-2225-002)

The main inclusion and exclusion criteria include but are not limited to the following: Inclusion Criteria: * Participants must have SSc, as defined using the 2013 American College of Rheumatology/European League Against Rheumatism criteria * If participant is on a non-excluded immunosuppressive therapy (e.g. mycophenolate, methotrexate, azathioprine, etc.) the dose should be stable for \> 2 months at the time of screening * Women of childbearing potential must: * If sexually active, have used, and agree to use, highly effective contraception without interruption, for at least 28 days prior to starting investigational product, during the study (including dose interruptions), and for 17 weeks (119 days) after discontinuation of study treatment * Refrain from breastfeeding a child or donating blood, eggs, or ovum for the duration of the study and for at least 17 weeks (119 days) after the last dose of study treatment * Male participants must: * Agree to use a condom, defined as a male latex condom or nonlatex condom NOT made out of natural (animal) membrane (e.g., polyurethane), during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions, and for at least 17 weeks (119 days) following investigational product discontinuation, even if he has undergone a successful vasectomy * Refrain from donating blood or sperm for the duration of the study and for 17 weeks (119 days) after the last dose of study treatment * Must agree to not participate in any other study of investigational drugs/devices while enrolled in this study Exclusion Criteria: * Participant with SSc-pulmonary arterial hypertension (PAH) (except those participants with mild PAH on up to 2 oral drugs and mean pulmonary arterial pressure \< 30 mmHg or low risk by risk calculator) * In the opinion of the investigator, other clinically significant pulmonary abnormalities (such as obstructive lung disease, asthma, etc.) * Other investigational therapy received within 1 month or 6 half-lives (whichever is greater) prior to the Screening Visit * Prior exposure to MK-2225 or other TGF-β antibodies or any TGF-β family targeted biologic or hypersensitivity to the components of MK-2225 * Hypersensitivity to placebo or any of its components * Previous hematopoietic stem cell transplantation (HSCT) or HSCT planned within the next year * Major surgical procedures planned during the study period * Oral prednisone or equivalent \> 10 mg/day * Participant with history of gastric antral vascular ectasia or gastrointestinal bleed * On anticoagulation therapy (such as prophylaxis anticoagulation, warfarin, direct thrombin inhibitors or other including low molecular weight subcutaneous or intravenous therapeutic heparin), or antiplatelet therapy including aspirin. Use of fish oil supplements within 2 weeks prior to randomization and throughout study is not permitted. * History of any other medical condition that might interfere with a participant's ability to participate in the study * Active clinically significant viral, bacterial, or fungal infection, or any episode of infection requiring hospitalization within 4 weeks prior to screening * Use of cyclophosphamide ≤ 6 months from screening * Use of nintedanib or pirfenidone ≤ 28 days from screening * Recent scleroderma renal crisis \< 6 months before screening * Use of tocilizumab ≤ 2 months from screening * Has received any nonlive vaccine starting from 14 days prior to study intervention or is scheduled to receive any nonlive vaccine through 30 days following study intervention. Exception: COVID-19 vaccine may be administered.