A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of RO7303509 in Participants With Systemic Sclerosis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of RO7303509 treatment in participants with systemic sclerosis (SSc) during a multiple-ascending-dose (MAD) portion of the trial. In the MAD phase, increasing doses of study drug will be tested sequentially. For each dose tested, the MAD stage will consist of a treatment period of 12 weeks followed by either a safety follow-up period of 13 weeks or continued treatment in an optional open-label safety extension (OSE) stage of 52 weeks to assess the long-term safety. All patients in the OSE stage will receive RO7303509 and no patient will receive placebo.

Official Title
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A Phase Ib, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Multiple-Ascending Doses of RO7303509 in Participants With Systemic Sclerosis

Conditions
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Systemic Sclerosis

Intervention / Treatment
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* Drug: RO7303509
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion Criteria for the MAD Stage: Weight of 45-150 kg at screening Diagnosis of SSc, as defined by 2013 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria and ≤ 10 years disease duration from first non-Raynaud's symptom Agreement to remain abstinent or use an effective contraceptive method among males and females with childbearing potential for 4 months after last dose of study drug Inclusion Criteria for the OSE Stage: No clinically significant change in eligibility status Completion of the MAD and ability to roll over into the OSE within 5 days Exclusion Criteria: Active rheumatic autoimmune disease other than SSc requiring treatment with disease-modifying therapy Pulmonary disease with forced vital capacity (FVC) ≤ 50% of predicted History or clinical manifestations of significant metabolic, hepatic, renal, pulmonary, cardiovascular, hematologic, gastrointestinal, urologic, neurologic, or psychiatric disorders History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies Pregnant or breastfeeding, or intending to become pregnant during the study or within 4 months after the final dose of study drug Major surgery within 8 weeks prior to screening, or major planned surgery during the study or within 3 months after the final dose Positive hepatitis C virus (HCV) antibody, hepatitis B surface antigen (HBsAg), or human immunodeficiency virus (HIV) antibody test at screening Any serious medical condition or abnormality in clinical laboratory tests

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MAD Stage<br>Participants will be randomized in a ratio of 4:1 to receive RO7303509 or placebo, as subcutaneous (SC) injection, one time per month for 3 months. You have a 20% chance of getting placebo. | Drug: RO7303509<br>* RO7303509 will be administered as SC injection monthly, as specified in each treatment group.<br>Drug: Placebo<br>* RO7303509 matching placebo will be administered as SC injection monthly, during the MAD stage.<br>|
| Experimental: OSE Stage<br>Every participant in the OSE stage will receive study drug and no participant will receive placebo. Participants will receive RO7303509 as SC injection at the same dose as that administered during the MAD stage, one time per month for up to a year. | Drug: RO7303509<br>* RO7303509 will be administered as SC injection monthly, as specified in each treatment group.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) |  | Up to approximately 17 months | 
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs |  | Up to approximately 17 months | 
| Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Test Results |  | Up to approximately 17 months | 
| Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Parameters |  | Up to approximately 17 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MAD Stage: Maximum Serum Concentration (Cmax) of RO7303509 |  | Predose on Day 1 and at multiple timepoints up to Day 113 or early termination (ET) visit | 
| MAD Stage: Area Under the Concentration vs Time Curve (AUC) of RO7303509 |  | Predose on Day 1 and at multiple timepoints up to Day 113 or ET visit | 
| MAD Stage: Time to Maximum Concentration (Tmax) of RO7303509 |  | Predose on Day 1 and at multiple timepoints up to Day 113 or ET visit | 
| MAD Stage: Total Clearance (CL) of RO7303509 |  | Predose on Day 1 and at multiple timepoints up to Day 113 or ET visit | 
| MAD Stage: Volume of Distribution (V) of RO7303509 |  | Predose on Day 1 and at multiple timepoints up to Day 113 or ET visit | 
| MAD Stage: Half-Life (t1/2) of RO7303509 |  | Predose on Day 1 and at multiple timepoints up to Day 113 or ET visit | 
| MAD and OSE Stage: Percentage of Participants With Anti-Drug Antibodies (ADAs) Against RO7303509 |  | MAD Stage: Predose on Day 1 and at multiple timepoints up to Day 113 (Week 16) or ET visit; OSE Stage: Predose and multiple timepoints up to Week 52; (up to approximately 1.3 years) |