Clinical trial NCT03824392: Study of Intravenous ATYR1923 (Efzofitimod) for Pulmonary Sarcoidosis
Official title: A Randomized, Double-Blind, Placebo-Controlled Multiple Ascending Dose Study of Intravenous ATYR1923 in Patients With Pulmonary Sarcoidosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
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)
Lead sponsor: aTyr Pharma, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Foundation for Sarcoidosis Research
First posted: 2019-01-31
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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 efzofitimod:placebo matched to efzofitimod
Primary purpose: TREATMENT

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).


Eligibility 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 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.

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 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.

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to Week 24
Secondary outcomes:
measure: Time-adjusted Area Under the Curve (AUC) of Background Oral Corticosteroid (OCS) Usage Over Study Period
timeFrame: Baseline up to Week 24 (Day 1 to End of Dosing Period)
measure: Number of Participants Who Achieved and Maintained The Targeted Tapered Dose of Prednisone 5 mg/Day (or Equivalent)
timeFrame: Baseline up to Week 24
measure: Number of Participants With Positive Anti-Drug Antibodies (Anti-Efzofitimod)
timeFrame: Baseline up to Week 24
measure: Number of Participants With at Least One Positive Anti-Jo-1 Antibodies Titers
timeFrame: Baseline up to Week 24
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Northridge
country: United States
facility: aTyr Investigative Site
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Miami
country: United States
facility: aTyr Investigative Site
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: aTyr Investigative Site
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Falls Church
country: United States
facility: Inova Fairfax Medical Center
state: Virginia
Study officials:
affiliation: aTyr Pharma, Inc.
name: Gennyne Walker
role: STUDY_DIRECTOR
References: