Purpose

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

Eligibility

Eligible Ages
Between 18 Years and 70 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 percent predicted; and
  • Positive 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (18F-FDG-PET/CT) scan showing increased metabolic activity in lung parenchyma within 4 weeks prior to Day 1.
  • 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 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.
  • Has been an active smoker (including e-cigarettes or e-vaporizers) within 3 months prior to Screening.
  • 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.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
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
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
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

Recruiting Locations

University of Alabama
Birmingham, Alabama 35294-0006
Contact:
Jospeh Barney, MD
205-996-5864
jbarney@uabmc.edu

More Details

NCT ID
NCT03824392
Status
Recruiting
Sponsor
aTyr Pharma, Inc.

Study Contact

aTyr Pharma Clinical Research
877-215-5731
clinicaltrials@atyrpharma.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.