Study of Intravenous ATYR1923 (Efzofitimod) for Pulmonary Sarcoidosis

aTyr Pharma

Status and phase: Completed; Phase 2; Phase 1

Conditions: Pulmonary Sarcoidosis

Treatments: Biological: Efzofitimod 3.0 mg/kg or Placebo; Biological: Efzofitimod 1.0 mg/kg or Placebo; Biological: Efzofitimod 5.0 mg/kg or Placebo

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03824392

ATYR1923-C-002

Details and patient eligibility

About

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).

Enrollment: 37 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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37 participants in 4 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

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

Treatment:

Biological: Efzofitimod 3.0 mg/kg or Placebo

Biological: Efzofitimod 1.0 mg/kg or Placebo

Biological: Efzofitimod 5.0 mg/kg or Placebo

Efzofitimod 1.0 mg/kg

Experimental group

Description:

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

Treatment:

Biological: Efzofitimod 1.0 mg/kg or Placebo

Efzofitimod 3.0 mg/kg

Experimental group

Description:

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

Treatment:

Biological: Efzofitimod 3.0 mg/kg or Placebo

Efzofitimod 5.0 mg/kg

Experimental group

Description:

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

Treatment:

Biological: Efzofitimod 5.0 mg/kg or Placebo