Study of Intravenous ATYR1923 for Pulmonary Sarcoidosis

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

  • Pulmonary Sarcoidosis

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