Study of Intravenous ATYR1923 (Efzofitimod) for Pulmonary Sarcoidosis

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

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).

Study Overview

• Status: Completed
• Conditions: Pulmonary Sarcoidosis
• Intervention / Treatment: Biological: Efzofitimod 1.0 mg/kg or Placebo; Biological: Efzofitimod 3.0 mg/kg or Placebo; Biological: Efzofitimod 5.0 mg/kg or Placebo

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-0006
      • University of Alabama
  • California
    • Northridge, California, United States, 91324
      • aTyr Investigative Site
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • Florida
    • Miami, Florida, United States, 33125
      • aTyr Investigative Site
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60612
      • aTyr Investigative Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville
  • North Carolina
    • Greenville, North Carolina, United States, 27858
      • East Carolina University
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • South Carolina
    • Charleston, South Carolina, United States, 92425
      • Medical University of South Carolina
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Fairfax Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 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; Participants to receive efzofitimod 1.0 mg/kg IV every 4 weeks or placebo matched to efzofitimod every 4 weeks; Biological: Efzofitimod 3.0 mg/kg or Placebo; Participants to receive efzofitimod 3.0 mg/kg IV every 4 weeks or placebo matched to efzofitimod every 4 weeks; Biological: Efzofitimod 5.0 mg/kg or Placebo; Participants to receive efzofitimod 5.0 mg/kg IV every 4 weeks or placebo matched to efzofitimod every 4 weeks
Experimental: Efzofitimod 1.0 mg/kg; 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; Participants to receive efzofitimod 1.0 mg/kg IV every 4 weeks or placebo matched to efzofitimod every 4 weeks
Experimental: Efzofitimod 3.0 mg/kg; 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; Participants to receive efzofitimod 3.0 mg/kg IV every 4 weeks or placebo matched to efzofitimod every 4 weeks
Experimental: Efzofitimod 5.0 mg/kg; 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; Participants to receive efzofitimod 5.0 mg/kg IV every 4 weeks or placebo matched to efzofitimod every 4 weeks

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: aTyr Pharma, Inc.
• Collaborators: Foundation for Sarcoidosis Research
• Investigators: Study Director: Gennyne Walker, aTyr Pharma, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 29, 2019
• Primary Completion (Actual): June 29, 2021
• Study Completion (Actual): June 29, 2021

Study Registration Dates

• First Submitted: January 28, 2019
• First Submitted That Met QC Criteria: January 29, 2019
• First Posted (Actual): January 31, 2019

Study Record Updates

• Last Update Posted (Actual): July 18, 2023
• Last Update Submitted That Met QC Criteria: June 27, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Inflammation; Sarcoidosis; Steroids; Lymphoproliferative Disorders; Pulmonary Sarcoidosis; Interstitial Lung Disease; Immunomodulatory; Oral corticosteroids; Neuropilin-2; tRNA Synthetase; Resokine; Granulomas; ATYR1923 (efzofitimod)
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Lung Diseases; Hypersensitivity; Lung Diseases, Interstitial; Hypersensitivity, Delayed; Sarcoidosis, Pulmonary; Sarcoidosis
• Other Study ID Numbers: ATYR1923-C-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No