Study of Intravenous ATYR1923 for Pulmonary Sarcoidosis

• ClinicalTrials.gov Identifier: NCT03824392
• Recruitment Status: Completed
• First Posted: January 31, 2019
• Last Update Posted: July 22, 2021
• Sponsor: aTyr Pharma, Inc.
• Collaborator: Foundation for Sarcoidosis Research
• Information provided by (Responsible Party): aTyr Pharma, Inc.

Study Description

Brief Summary:

This randomized, double-blind, placebo-controlled, study will evaluate the safety, tolerability, immunogenicity, pharmacokinetic (PK), and preliminary efficacy of multiple ascending doses of IV ATYR1923 in patients 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 ATYR1923 (N=8) or placebo (N=4).

Condition or disease	Intervention/treatment	Phase
Pulmonary Sarcoidosis	Biological: ATYR1923 1.0 mg/kg or placebo; Biological: ATYR1923 3.0 mg/kg or placebo; Biological: ATYR1923 5.0 mg/kg or placebo	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 37 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: 36 participants with pulmonary sarcoidosis will be randomized into one of 3 sequential cohorts, each comprising 12 participants allocated 2:1 to ATYR1923:Placebo
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled Multiple Ascending Dose Study of Intravenous ATYR1923 in Patients With Pulmonary Sarcoidosis
• Actual Study Start Date: January 29, 2019
• Actual Primary Completion Date: June 29, 2021
• Actual Study Completion Date: June 29, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort 1; ATYR1923 1.0 mg/kg or placebo	Biological: ATYR1923 1.0 mg/kg or placebo; ATYR1923 participants to receive ATYR1923 1.0 mg/kg IV every 4 weeks; Placebo participants to receive placebo IV every 4 weeks
Experimental: Cohort 2; ATYR1923 3.0 mg/kg or placebo	Biological: ATYR1923 3.0 mg/kg or placebo; ATYR1923 participants to receive ATYR1923 3.0 mg/kg IV every 4 weeks; Placebo participants to receive placebo IV every 4 weeks
Experimental: Cohort 3; ATYR1923 5.0 mg/kg or placebo	Biological: ATYR1923 5.0 mg/kg or placebo; ATYR1923 participants to receive ATYR1923 5.0 mg/kg IV every 4 weeks; Placebo participants to receive placebo IV every 4 weeks

Outcome Measures

Primary Outcome Measures :

1. Incidence of treatment emergent adverse events and serious adverse events [ Time Frame: Baseline to Week 24 ]

Secondary Outcome Measures :

1. Total cumulative steroid dose administered over study period [ Time Frame: Baseline to Week 24 ]
2. Number of participants who achieve and maintain the targeted tapered dose of prednisone 5 mg/kg day [ Time Frame: Baseline to Week 24 ]
3. Exposure response analysis comparing steroid dose area under the curve (AUC) with ATYR1923 PK parameters [ Time Frame: Baseline to Week 24 ]
4. Incidence and titer of positive anti-drug-antibodies (anti-ATYR1923) [ Time Frame: Baseline to Week 24 ]
5. Incidence and titer of anti-Jo-1 antibodies [ Time Frame: Baseline to Week 24 ]

Eligibility Criteria

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

Criteria

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 evidence 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 ATYR1923 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 their 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.
• Patient 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.

Contacts and Locations

Locations

United States, Alabama

University of Alabama

Birmingham, Alabama, United States, 35294-0006

United States, California

aTyr Investigative Site

Northridge, California, United States, 91324

United States, Colorado

National Jewish Health

Denver, Colorado, United States, 80206

United States, Florida

aTyr Investigative Site

Miami, Florida, United States, 33125

United States, Georgia

Emory University

Atlanta, Georgia, United States, 30322

United States, Illinois

Northwestern University

Chicago, Illinois, United States, 60611

aTyr Investigative Site

Chicago, Illinois, United States, 60612

United States, Iowa

University of Iowa

Iowa City, Iowa, United States, 52242

United States, Kentucky

University of Louisville

Louisville, Kentucky, United States, 40202

United States, North Carolina

East Carolina University

Greenville, North Carolina, United States, 27858

United States, Ohio

University of Cincinnati

Cincinnati, Ohio, United States, 45267

Cleveland Clinic

Cleveland, Ohio, United States, 44195

United States, South Carolina

Medical University of South Carolina

Charleston, South Carolina, United States, 92425

United States, Texas

UT Southwestern Medical Center

Dallas, Texas, United States, 75390

United States, Virginia

Inova Fairfax Medical Center

Falls Church, Virginia, United States, 22042

Sponsors and Collaborators

aTyr Pharma, Inc.

Foundation for Sarcoidosis Research

Investigators

• Study Director: Gennyne Walker; aTyr Pharma, Inc.

More Information

• Responsible Party: aTyr Pharma, Inc.
• ClinicalTrials.gov Identifier: NCT03824392
• Other Study ID Numbers: ATYR1923-C-002
• First Posted: January 31, 2019
• Last Update Posted: July 22, 2021
• Last Verified: July 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by aTyr Pharma, Inc.:

ATYR1923; Pulmonary Sarcoidosis; Resokine; Sarcoidosis; Granulomas; Inflammation; Lymphoproliferative Disorders; Interstitial Lung Disease; Neuropilin-2; Steroids; Oral corticosteroids; Immunomodulatory; tRNA Synthetase

Additional relevant MeSH terms:

Sarcoidosis, Pulmonary; Sarcoidosis; Lymphoproliferative Disorders; Lymphatic Diseases; Hypersensitivity, Delayed; Hypersensitivity; Immune System Diseases; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases