Study of Intravenous ATYR1923 (Efzofitimod) for Pulmonary Sarcoidosis

NCT ID: NCT03824392

Last Updated: 2023-07-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-29
• Study Completion Date: 2021-06-29

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Participants will receive placebo matched to efzofitimod via intravenous (IV) infusion every 4 weeks until Week 20.

Group Type: PLACEBO_COMPARATOR

Efzofitimod 1.0 mg/kg or Placebo

Intervention Type: BIOLOGICAL

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

Efzofitimod 3.0 mg/kg or Placebo

Intervention Type: BIOLOGICAL

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

Efzofitimod 5.0 mg/kg or Placebo

Intervention Type: BIOLOGICAL

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

Efzofitimod 1.0 mg/kg

Participants will receive efzofitimod 1.0 milligrams/kilogram (mg/kg) via IV infusion every 4 weeks until Week 20.

Group Type: EXPERIMENTAL

Efzofitimod 1.0 mg/kg or Placebo

Intervention Type: BIOLOGICAL

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

Efzofitimod 3.0 mg/kg

Participants will receive efzofitimod 3.0 mg/kg via IV infusion every 4 weeks until Week 20.

Group Type: EXPERIMENTAL

Efzofitimod 3.0 mg/kg or Placebo

Intervention Type: BIOLOGICAL

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

Efzofitimod 5.0 mg/kg

Participants will receive efzofitimod 5.0 mg/kg via IV infusion every 4 weeks until Week 20.

Group Type: EXPERIMENTAL

Efzofitimod 5.0 mg/kg or Placebo

Intervention Type: BIOLOGICAL

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

Interventions

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

Intervention Type: 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

Intervention Type: 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

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Foundation for Sarcoidosis Research

OTHER

Sponsor Role: collaborator

aTyr Pharma, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gennyne Walker

Role: STUDY_DIRECTOR

aTyr Pharma, Inc.

Locations

University of Alabama

Birmingham, Alabama, United States

aTyr Investigative Site

Northridge, California, United States

National Jewish Health

Denver, Colorado, United States

aTyr Investigative Site

Miami, Florida, United States

Emory University

Atlanta, Georgia, United States

Northwestern University

Chicago, Illinois, United States

aTyr Investigative Site

Chicago, Illinois, United States

University of Iowa

Iowa City, Iowa, United States

University of Louisville

Louisville, Kentucky, United States

East Carolina University

Greenville, North Carolina, United States

University of Cincinnati

Cincinnati, Ohio, United States

Cleveland Clinic

Cleveland, Ohio, United States

Medical University of South Carolina

Charleston, South Carolina, United States

UT Southwestern Medical Center

Dallas, Texas, United States

Inova Fairfax Medical Center

Falls Church, Virginia, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 37854715 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36356657 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

ATYR1923-C-002

Identifier Type: -

Identifier Source: org_study_id