Study of Intravenous ATYR1923 (Efzofitimod) for Pulmonary Sarcoidosis

Study Overview
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Brief Summary
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This randomized, double-blind, placebo matched to efzofitimod-controlled, study will evaluate the safety, tolerability, immunogenicity, pharmacokinetic (PK), and preliminary efficacy of multiple ascending doses of IV efzofitimod in participants with pulmonary sarcoidosis undergoing a protocol-guided oral corticosteroid (OCS) tapering regimen.This study will consist of 3 staggered multiple dose cohorts. Each eligible participant will participate in only one cohort during the study. Within each cohort, 12 participants will be randomized 2:1 to efzofitimod (N=8) or placebo matched to efzofitimod (N=4).

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Multiple Ascending Dose Study of Intravenous ATYR1923 in Patients With Pulmonary Sarcoidosis

Conditions
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Pulmonary Sarcoidosis

Intervention / Treatment
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* Biological: Efzofitimod 1.0 mg/kg or Placebo
* Biological: Efzofitimod 3.0 mg/kg or Placebo
* Biological: Efzofitimod 5.0 mg/kg or Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Diagnosis of pulmonary sarcoidosis for ≥6 months (cutaneous and ocular involvement allowed), defined as: Histologically proven diagnosis of sarcoidosis by bronchoscopy, biopsy (any organ) or bronchioalveolar lavage Parenchymal lung involvement by historical radiological evidence Must have symptomatic and/or active pulmonary sarcoidosis as evidenced by: Modified Medical Research Council Dyspnea Scale grade of >= 1; and Forced vital capacity ≥50%; and Receiving treatment with 10 to 25 mg/day of oral prednisone (or equivalent), at a stable dose for ≥4 weeks prior to Day 1, and capable of undergoing the protocol-specified steroid taper regimen. Body weight ≥45 kg and <160 kg. Key Exclusion Criteria: Current disease presentation consistent with Lofgren's syndrome. History of severe allergic or anaphylactic reactions to therapeutic proteins or known sensitivity to efzofitimod or to its inactive components (L-histidine, sodium chloride, sucrose, L-methionine, and polysorbate-20). Treatment with biological immunomodulators such as tumor necrosis factor-alpha inhibitors. Current evidence of clinically significant cardiovascular, hepatic, renal, hematological, metabolic, or gastrointestinal disease, or has a condition that requires other treatment. Clinically significant pulmonary hypertension requiring vasodilator treatment. Any history of tuberculosis or evidence of active systemic non-tuberculosis fungal or mycobacterial infection within 1 year of Screening. History of clinically significant cardiac, neurological, gastrointestinal, and/or renal manifestations of sarcoidosis. Any condition that necessitated hospitalization within the 3 months prior to Day 1 or is likely to require so during the study. Participation in another clinical study of an investigational agent or device within 3 months (small molecules) / 6 months (biologics) or 5 half-lives (if known) of the agent, whichever is longer. History of or positive results of screening for hepatitis B, hepatitis C or human immunodeficiency virus. Is an active, heavy smoker of tobacco/nicotine-containing products (defined as >20 cigarettes/day or e-cigarette equivalent). Active substance abuse or history of substance abuse within the 12 months prior to Screening. Participant has received a live vaccination within 8 weeks before Day 1 or inoculation with a live vaccine is planned during study participation. Positive for Jo-1 antibodies (Ab) at Screening, or past history of Jo-1 Ab positivity. Significant and/or acute illness within 5 days prior to drug administration that may impact safety assessments, in the opinion of the Investigator.

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
Interventional Model Description: 36 participants with pulmonary sarcoidosis will be randomized into one of 3 sequential cohorts, each comprising 12 participants allocated 2:1 to efzofitimod:placebo matched to efzofitimod
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants will receive placebo matched to efzofitimod via intravenous (IV) infusion every 4 weeks until Week 20. | Biological: Efzofitimod 1.0 mg/kg or Placebo<br>* Participants to receive efzofitimod 1.0 mg/kg IV every 4 weeks or placebo matched to efzofitimod every 4 weeks<br>Biological: Efzofitimod 3.0 mg/kg or Placebo<br>* Participants to receive efzofitimod 3.0 mg/kg IV every 4 weeks or placebo matched to efzofitimod every 4 weeks<br>Biological: Efzofitimod 5.0 mg/kg or Placebo<br>* Participants to receive efzofitimod 5.0 mg/kg IV every 4 weeks or placebo matched to efzofitimod every 4 weeks<br>|
| Experimental: Efzofitimod 1.0 mg/kg<br>Participants will receive efzofitimod 1.0 milligrams/kilogram (mg/kg) via IV infusion every 4 weeks until Week 20. | Biological: Efzofitimod 1.0 mg/kg or Placebo<br>* Participants to receive efzofitimod 1.0 mg/kg IV every 4 weeks or placebo matched to efzofitimod every 4 weeks<br>|
| Experimental: Efzofitimod 3.0 mg/kg<br>Participants will receive efzofitimod 3.0 mg/kg via IV infusion every 4 weeks until Week 20. | Biological: Efzofitimod 3.0 mg/kg or Placebo<br>* Participants to receive efzofitimod 3.0 mg/kg IV every 4 weeks or placebo matched to efzofitimod every 4 weeks<br>|
| Experimental: Efzofitimod 5.0 mg/kg<br>Participants will receive efzofitimod 5.0 mg/kg via IV infusion every 4 weeks until Week 20. | Biological: Efzofitimod 5.0 mg/kg or Placebo<br>* Participants to receive efzofitimod 5.0 mg/kg IV every 4 weeks or placebo matched to efzofitimod every 4 weeks<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) and Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. TEAEs were defined as any adverse event or worsening of an existing condition after initiation of the investigational product and through 30 days after the participant's last study visit (study completion or early termination). SAEs included death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'. | Baseline up to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-adjusted Area Under the Curve (AUC) of Background Oral Corticosteroid (OCS) Usage Over Study Period | Time adjusted AUC is a measure of steroid burden and approximates the average daily OCS dose (mg/day) post-baseline for each participant. Time adjusted AUC was calculated by AUC divided by the number of days between first and last day of time interval of interest. | Baseline up to Week 24 (Day 1 to End of Dosing Period) | 
| Number of Participants Who Achieved and Maintained The Targeted Tapered Dose of Prednisone 5 mg/Day (or Equivalent) |  | Baseline up to Week 24 | 
| Number of Participants With Positive Anti-Drug Antibodies (Anti-Efzofitimod) | The number of all participants having drug reactive antibodies at any point in time (efzofitimod and placebo matched to efzofitimod) have been reported. | Baseline up to Week 24 | 
| Number of Participants With at Least One Positive Anti-Jo-1 Antibodies Titers |  | Baseline up to Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Inflammation, Lymphoproliferative Disorders, Interstitial Lung Disease, Neuropilin-2, Steroids, Oral corticosteroids, Immunomodulatory, tRNA Synthetase, ATYR1923 (efzofitimod), Pulmonary Sarcoidosis, Resokine, Sarcoidosis, Granulomas