A Phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of intravenous efzofitimod in patients with pulmonary sarcoidosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

aTYR Pharma Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

12 Apr 2023 → 14 Jul 2025

Decision date (initial)

2023-07-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2023-506039-13-00

EudraCT number

2022-001012-26

WHO UTN

U1111-1292-9476

ClinicalTrials.gov

NCT05415137

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Therapy, Efficacy, Pharmacodynamic, Safety

To assess the efficacy of efzofitimod in patients with pulmonary sarcoidosis

Secondary objectives 2

1. 1. To assess the safety and tolerability of efzofitimod in patients with pulmonary sarcoidosis
2. 2. To explore the utility of serum biomarkers in the evaluation of interventions to treat pulmonary sarcoidosis

Conditions and MedDRA coding

pulmonary sarcoidosis

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-003352-PIP01-22

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 1. Male or females aged 18 to 75 years, inclusive at the time of informed consent
2. 2. 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
3. 3. 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
4. 4. Patients must be receiving treatment with OCS of ≥ 3 months with a starting dose between ≥ 7.5 and ≤ 25 mg/day.
5. 5. Body weight ≥ 40 kg and < 160 kg
6. 6. 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
7. 7. Provide written informed consent
8. 8. Agree to comply with all study procedures and requirements

Exclusion criteria 18

1. 1. 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
2. 2. Treatment with > 1 oral immunosuppressant therapy
3. 3. Treatment with biological immunomodulators, such as tumor necrosis factor-alpha (TNF-α) inhibitors or antifibrotics or interleukin inhibitors
4. 4. 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
5. 5. Clinically significant bronchiectasis or cavitary sarcoidosis with mycetoma at Screening or during the previous 12 months
6. 6. Clinically significant pulmonary hypertension requiring treatment with vasodilators
7. 7. Patients with cardiac sarcoidosis, neurosarcoidosis, or renal sarcoidosis
8. 8. Clinically significant cutaneous and ocular sarcoidosis
9. 9. History of Addisonian symptoms that precluded previous OCS taper attempts
10. 10. 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)
11. 11. 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
12. 12. 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
13. 13. Major surgery or hospitalization within 3 months prior to Day 1 or anticipated surgery during the study
14. 14. 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
15. 15. Is an active, heavy smoker of tobacco/nicotine-containing products
16. 16. Active substance abuse (drugs, alcohol, or cannabis) or history of substance abuse within 12 months prior to Screening
17. 17. 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
18. 18. History of anti-synthetase syndrome or Jo-1 positive at baseline

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in mean daily OCS dose at Week 48

Secondary endpoints 3

1. 1. Steroid-free rate at Week 48
2. 2. Steroid-free and stable KSQ-Lung composite rate at Week 48
3. 3. Change from baseline in absolute value of FVC at Week 48

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

aTYR Pharma Inc.

Sponsor organisation

aTYR Pharma Inc.

Address

10240 Sorrento Valley Road Suite 300

City

San Diego

Postcode

92121-1605

Country

United States

Scientific contact point

Organisation

aTYR Pharma Inc.

Contact name

Regulatory Submissions

Public contact point

Organisation

aTYR Pharma Inc.

Contact name

Regulatory Submissions

Third parties 11

Locations

5 EU/EEA countries · 27 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 131 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

17 submissions — initial application plus substantial / non-substantial modifications