Study of Intravenous ATYR1923 (Efzofitimod) for Pulmonary Sarcoidosis

NCT03824392 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: ATYR1923-C-002
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 15

Brief Summary

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).

Conditions

Pulmonary Sarcoidosis

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Time-adjusted Area Under the Curve (AUC) of Background Oral Corticosteroid (OCS) Usage Over Study Period

  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)

  Baseline up to Week 24

• Number of Participants With at Least One Positive Anti-Jo-1 Antibodies Titers

  Baseline up to Week 24

Study Arms (4)

Placebo

PLACEBO COMPARATOR

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; Biological: Efzofitimod 3.0 mg/kg or Placebo; Biological: Efzofitimod 5.0 mg/kg or Placebo

Efzofitimod 1.0 mg/kg

EXPERIMENTAL

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

Efzofitimod 3.0 mg/kg

EXPERIMENTAL

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

Efzofitimod 5.0 mg/kg

EXPERIMENTAL

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

Interventions

Efzofitimod 1.0 mg/kg or Placebo BIOLOGICAL

Participants to receive efzofitimod 1.0 mg/kg IV every 4 weeks or placebo matched to efzofitimod every 4 weeks

Efzofitimod 1.0 mg/kg; Placebo

Efzofitimod 3.0 mg/kg or Placebo BIOLOGICAL

Participants to receive efzofitimod 3.0 mg/kg IV every 4 weeks or placebo matched to efzofitimod every 4 weeks

Efzofitimod 3.0 mg/kg; Placebo

Efzofitimod 5.0 mg/kg or Placebo BIOLOGICAL

Participants to receive efzofitimod 5.0 mg/kg IV every 4 weeks or placebo matched to efzofitimod every 4 weeks

Efzofitimod 5.0 mg/kg; Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• aTyr Pharma, Inc.: lead
• Foundation for Sarcoidosis Research: collaborator

Study Sites (15)

University of Alabama

Birmingham, Alabama, 35294-0006, United States

Location

aTyr Investigative Site

Northridge, California, 91324, United States

Location

National Jewish Health

Denver, Colorado, 80206, United States

Location

aTyr Investigative Site

Miami, Florida, 33125, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

aTyr Investigative Site

Chicago, Illinois, 60612, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

East Carolina University

Greenville, North Carolina, 27858, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 92425, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Inova Fairfax Medical Center

Falls Church, Virginia, 22042, United States

Location

Related Publications (2)

• Walker G, Adams R, Guy L, Chandrasekaran A, Kinnersley N, Ramesh P, Zhang L, Brown F, Niranjan V. Exposure-response analyses of efzofitimod in patients with pulmonary sarcoidosis. Front Pharmacol. 2023 Oct 3;14:1258236. doi: 10.3389/fphar.2023.1258236. eCollection 2023.

  PMID: 37854715 DERIVED

• Culver DA, Aryal S, Barney J, Hsia CCW, James WE, Maier LA, Marts LT, Obi ON, Sporn PHS, Sweiss NJ, Shukla S, Kinnersley N, Walker G, Baughman R. Efzofitimod for the Treatment of Pulmonary Sarcoidosis. Chest. 2023 Apr;163(4):881-890. doi: 10.1016/j.chest.2022.10.037. Epub 2022 Nov 8.

  PMID: 36356657 DERIVED

MeSH Terms

Conditions

Sarcoidosis, Pulmonary; Sarcoidosis; Granuloma; Inflammation; Lymphoproliferative Disorders; Lung Diseases, Interstitial

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Lymphatic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Delayed; Hypersensitivity; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Immunoproliferative Disorders

Results Point of Contact

• Title: Lisa Carey
• Organization: aTyR Pharma

clinicaltrials@atyrpharma.com

858 731 8389

Study Officials

• Gennyne Walker

  aTyr Pharma, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: January 28, 2019
• First Posted: January 31, 2019
• Study Start: January 29, 2019
• Primary Completion: June 29, 2021
• Study Completion: June 29, 2021
• Last Updated: July 18, 2023
• Results First Posted: July 18, 2023

Record last verified: 2023-06

Locations

US (15)