Phase 3 Randomized Double-Blind Placebo-Controlled Trial Evaluating Intravenous Efzofitimod Efficacy and Safety in Pulmonary Sarcoidosis Patients

Trial ID: 2023-506039-13-00
Protocol: ATYR1923-C-004
Sponsor: aTYR Pharma Inc.

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Diseases & Conditions

Pulmonary sarcoidosis

Objectives

The primary objective of this Phase 3, randomized, double-blind, placebo-controlled study is to assess the **efficacy** of intravenous efzofitimod in patients with **pulmonary sarcoidosis**. This objective is clinically relevant as it aims to determine the therapeutic potential of efzofitimod in managing this chronic inflammatory disease, which can significantly impact respiratory function and quality of life.

Secondary objectives include: - To assess the **safety** and tolerability of efzofitimod in patients with pulmonary sarcoidosis. - To explore the utility of serum **biomarkers** in the evaluation of interventions to treat pulmonary sarcoidosis. These objectives are crucial for understanding the broader implications of efzofitimod treatment, including its safety profile and potential biomarkers that could guide future therapeutic strategies.

Participants

The clinical trial investigating the efficacy of efzofitimod in patients with **pulmonary sarcoidosis** includes a total of 185 participants. The study population comprises both male and female subjects, aged between 18 and 75 years. Participants were selected based on a confirmed diagnosis of pulmonary sarcoidosis for at least six months, with documented histological evidence and parenchymal lung involvement. The trial does not involve a vulnerable population. Participants are required to have a symptomatic presentation of the disease, as indicated by a Modified Medical Research Council Dyspnea Scale grade of at least 1 and a KSQ-Lung score of 70 or less. All participants must have been receiving oral corticosteroids for at least three months, with a starting dose between 7.5 and 25 mg/day. The study includes individuals with a body weight ranging from 40 kg to less than 160 kg. Female participants of childbearing potential must not be pregnant or lactating and are required to use effective contraception during the study period. The trial ensures that all participants have provided written informed consent and agree to comply with study procedures and requirements.

Plans and Procedures

The clinical trial is a **Phase 3**, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of intravenous **efzofitimod** in patients with **pulmonary sarcoidosis**. The trial aims to assess the change from baseline in mean daily oral corticosteroid (OCS) dose post-taper as the primary endpoint. Secondary endpoints include the annual rate of change in the absolute value of forced vital capacity (FVC), percent change from baseline in mean daily OCS dose post-taper, and change from baseline in KSQ-Lung score at Week 48. The trial is expected to last approximately 18 months, with an estimated recruitment start date of June 15, 2023, and an estimated end date of December 15, 2024.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, confirmed diagnosis of pulmonary sarcoidosis, and current treatment with OCS. Following the screening, eligible participants will be randomized to receive either efzofitimod or placebo via intravenous injection. The study includes regular follow-up visits to monitor safety, efficacy, and any changes in the participants' condition. The end-of-study visit will occur at the conclusion of the 48-week treatment period, where final assessments will be conducted.

Participant involvement is expected to last for the duration of the trial, approximately 48 weeks, with conditions for early termination including withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety. The trial is conducted in accordance with ethical guidelines and regulatory requirements, ensuring the integrity and scientific validity of the study outcomes.

Treatment

The clinical trial involves the administration of **Efzofitimod**, an experimental medication, to evaluate its efficacy and safety in patients with pulmonary sarcoidosis. **Efzofitimod** is provided in the form of an **injection** and is administered via **intravenous use**. The dosage is calculated based on the patient's body weight, with a maximum daily dose of 5 mg/kg and a total maximum dose of 60 mg/kg over the treatment period. The treatment duration is set for a maximum of 48 weeks. **Efzofitimod** is a protein-based therapeutic agent, specifically a fusion protein derived from the Human HARS Fusion Protein, and is developed by ATYR PHARMA INC. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the protocol.

In addition to the experimental treatment, the study includes the use of **electrolyte solutions** as a non-experimental treatment. These solutions are classified under the ATC code B05XA and are administered intravenously. The maximum daily volume of the electrolyte solution is 250 ml, with a total maximum volume of 3000 ml over the 48-week treatment period. The electrolyte solutions serve as a comparator treatment to assess the relative efficacy and safety of **Efzofitimod**. The administration of these solutions will be conducted in accordance with standard clinical practices, and participant compliance will be monitored to ensure accurate data collection and analysis.

Efficacy

The efficacy of intravenous **efzofitimod** in patients with pulmonary sarcoidosis will be assessed in a Phase 3, randomized, double-blind, placebo-controlled clinical trial. The primary endpoint for evaluating efficacy is the change from baseline in the mean daily oral corticosteroid (OCS) dose post-taper. Secondary endpoints include the annual rate of change in the absolute value of forced vital capacity (FVC), the percent change from baseline in the mean daily OCS dose post-taper, and the change from baseline in the King's Sarcoidosis Questionnaire (KSQ)-Lung score at Week 48.

These efficacy parameters will be measured and collected at specified timepoints throughout the trial, with the final assessment occurring at the end of the 48-week treatment period. The KSQ-Lung score, a patient-reported outcome measure, will be utilized to evaluate symptom improvement. The trial will ensure the use of validated scales and laboratory tests to accurately capture and analyze the data related to these endpoints. The study is designed to provide robust evidence on the efficacy of efzofitimod in reducing corticosteroid use and improving lung function and quality of life in patients with pulmonary sarcoidosis.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Male or females aged 18 to 75 years, inclusive at the time of informed consent
Confirmed diagnosis of pulmonary sarcoidosis for at least 6 months, defined by the following criteria: documented histologically proven diagnosis of sarcoidosis by tissue biopsy and documented evidence of parenchymal lung involvement by historical radiological evidence
Evidence of symptomatic pulmonary sarcoidosis, as demonstrated by the following criteria: a. Modified Medical Research Council (MRC) Dyspnea Scale grade of at least 1 b. KSQ-Lung score ≤70
Patients must be receiving treatment with OCS of ≥ 3 months with a starting dose between ≥ 7.5 and ≤ 25 mg/day.
Body weight ≥ 40 kg and < 160 kg
If female of childbearing potential, must a. Not be pregnant or lactating, and have a negative pregnancy test at Screening (serum) and at Day 1 (urine) prior to first study drug infusion b. Be willing to use acceptable or highly effective methods of contraception from Screening until 8 weeks after the last study drug administration (refer to Appendix 6 for acceptable and highly effective methods of contraception) Note: To be considered of non-childbearing potential, the patient must be either surgically sterile or postmenopausal (confirmed by amenorrhea duration of at least 12 months with no alternative medical cause
Provide written informed consent
Agree to comply with all study procedures and requirements

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Exclusion Criteria

Current disease presentation consistent with Lofgren’s syndrome (ie, presence of the triad of erythema nodosum, bilateral hilar lymphadenopathy on chest X-ray, and joint pain
Treatment with > 1 oral immunosuppressant therapy
Treatment with biological immunomodulators, such as tumor necrosis factor-alpha (TNF-α) inhibitors or antifibrotics or interleukin inhibitors
Likelihood of significant pulmonary fibrosis as shown by any 1 or more of the following: a. CT fibrosis > 20% within the last 12 months b. FVC percent predicted (FVCPP) < 50% c. KSQ-Lung score < 30
Clinically significant bronchiectasis or cavitary sarcoidosis with mycetoma at Screening or during the previous 12 months
Clinically significant pulmonary hypertension requiring treatment with vasodilators
Patients with cardiac sarcoidosis, neurosarcoidosis, or renal sarcoidosis
Clinically significant cutaneous and ocular sarcoidosis
History of Addisonian symptoms that precluded previous OCS taper attempts
History of severe allergic or anaphylactic reactions to therapeutic proteins or known sensitivity to efzofitimod or its inactive components (L-histidine, sodium chloride, sucrose, L-methionine, and polysorbate-20)
In the opinion of the Investigator and Medical Monitor, current evidence of clinically significant cardiovascular, hepatic, neurological, renal, hematological, lymphatic, metabolic, or gastrointestinal disease, or any condition that requires other treatment or surgery, that may preclude the assessment of efficacy, confound the assessment of safety, or compromise patients’ compliance with study procedures
Active or history of malignancy within the last 5 years, except for resected basal cell carcinoma, squamous cell carcinoma of the skin, or effectively managed cervical carcinoma
Major surgery or hospitalization within 3 months prior to Day 1 or anticipated surgery during the study
Participation in another clinical study of an investigational agent or device within 3 months (small molecules and device), 6 months (biologics), or 5 half-lives (if known) of the agent, whichever is longer
Is an active, heavy smoker of tobacco/nicotine-containing products
Active substance abuse (drugs, alcohol, or cannabis) or history of substance abuse within 12 months prior to Screening
Clinically significant abnormalities in the Screening physical examination, vital signs, ECG, or clinical laboratory test results that, in the opinion of the Investigator and Medical Monitor, preclude the patient’s participation in the clinical study
History of anti-synthetase syndrome or Jo-1 positive at baseline

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
France	Not Recruiting	15 Jun 2023	19
Germany	Not Recruiting	15 Jun 2023	23
Italy	Not Recruiting	15 Jun 2023	33
The Netherlands	Not Recruiting	15 Jun 2023	—
Spain	Not Recruiting	15 Jun 2023	22
Netherlands	—	—	4