Pulmonary SarcoidosisPhase 1/2NCT03824392
Study of Intravenous ATYR1923 (Efzofitimod) for Pulmonary Sarcoidosis
A Phase 1/2 study of Pulmonary Sarcoidosis, run by aTyr Pharma, Inc. at 15 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Pulmonary Sarcoidosis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 37 participants
- Where
- 15 sitesUnited States
- Study dates
- 29 Jan 2019to 29 Jun 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 15Show fewer
- 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 locations and contacts
15 sites in 1 country.
15 sites in 1 country
United States15 sites
Emory University
Atlanta, Georgia, 30322
University of Alabama
Birmingham, Alabama, 35294-0006
Medical University of South Carolina
Charleston, South Carolina, 92425
Northwestern University
Chicago, Illinois, 60611
aTyr Investigative Site
Chicago, Illinois, 60612
University of Cincinnati
Cincinnati, Ohio, 45267
Cleveland Clinic
Cleveland, Ohio, 44195
UT Southwestern Medical Center
Dallas, Texas, 75390
National Jewish Health
Denver, Colorado, 80206
Inova Fairfax Medical Center
Falls Church, Virginia, 22042
East Carolina University
Greenville, North Carolina, 27858
University of Iowa
Iowa City, Iowa, 52242
University of Louisville
Louisville, Kentucky, 40202
aTyr Investigative Site
Miami, Florida, 33125
aTyr Investigative Site
Northridge, California, 91324
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled Multiple Ascending Dose Study of Intravenous ATYR1923 in Patients With Pulmonary Sarcoidosis
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).
- Conditions
- Pulmonary Sarcoidosis
- Being tested
- Efzofitimod 1.0 mg/kg or Placebo, Efzofitimod 3.0 mg/kg or Placebo, Efzofitimod 5.0 mg/kg or Placebo
- Keywords
- Pulmonary Sarcoidosis, Resokine, Sarcoidosis, Granulomas, Inflammation, Lymphoproliferative Disorders, Interstitial Lung Disease, Neuropilin-2, Steroids, Oral corticosteroids, Immunomodulatory, tRNA Synthetase, ATYR1923 (efzofitimod)
- Medical subject headings
- Sarcoidosis, Pulmonary, Sarcoidosis, Granuloma, Inflammation, Lymphoproliferative Disorders, Lung Diseases, Interstitial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Efzofitimod 1.0 mg/kg or PlaceboBiological
Participants to receive efzofitimod 1.0 mg/kg IV every 4 weeks or placebo matched to efzofitimod every 4 weeks
Efzofitimod 3.0 mg/kg or PlaceboBiological
Participants to receive efzofitimod 3.0 mg/kg IV every 4 weeks or placebo matched to efzofitimod every 4 weeks
Efzofitimod 5.0 mg/kg or PlaceboBiological
Participants to receive efzofitimod 5.0 mg/kg IV every 4 weeks or placebo matched to efzofitimod every 4 weeks
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Participants will receive placebo matched to efzofitimod via intravenous (IV) infusion every 4 weeks until Week 20. Receives: Biological: Efzofitimod 1.0 mg/kg or Placebo; Biological: Efzofitimod 3.0 mg/kg or Placebo; Biological: Efzofitimod 5.0 mg/kg or Placebo |
| Efzofitimod 1.0 mg/kg | Experimental | Participants will receive efzofitimod 1.0 milligrams/kilogram (mg/kg) via IV infusion every 4 weeks until Week 20. Receives: Biological: Efzofitimod 1.0 mg/kg or Placebo |
| Efzofitimod 3.0 mg/kg | Experimental | Participants will receive efzofitimod 3.0 mg/kg via IV infusion every 4 weeks until Week 20. Receives: Biological: Efzofitimod 3.0 mg/kg or Placebo |
| Efzofitimod 5.0 mg/kg | Experimental | Participants will receive efzofitimod 5.0 mg/kg via IV infusion every 4 weeks until Week 20. Receives: Biological: Efzofitimod 5.0 mg/kg or Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. TEAEs were defined as any adverse event or worsening of an existing condition after initiation of the investigational product and through 30 days after the participant's last study visit (study completion or early termination). SAEs included death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'.
Measured: Baseline up to Week 24
Secondary outcomes (4)
Time-adjusted Area Under the Curve (AUC) of Background Oral Corticosteroid (OCS) Usage Over Study Period
Time adjusted AUC is a measure of steroid burden and approximates the average daily OCS dose (mg/day) post-baseline for each participant. Time adjusted AUC was calculated by AUC divided by the number of days between first and last day of time interval of interest.
Measured: Baseline up to Week 24 (Day 1 to End of Dosing Period)
Number of Participants Who Achieved and Maintained The Targeted Tapered Dose of Prednisone 5 mg/Day (or Equivalent)
Measured: Baseline up to Week 24
Number of Participants With Positive Anti-Drug Antibodies (Anti-Efzofitimod)
The number of all participants having drug reactive antibodies at any point in time (efzofitimod and placebo matched to efzofitimod) have been reported.
Measured: Baseline up to Week 24
Number of Participants With at Least One Positive Anti-Jo-1 Antibodies Titers
Measured: Baseline up to Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2019
- Study start29 Jan 2019
- Primary completion29 Jun 2021
- Study completion29 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Pulmonary SarcoidosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- aTyr Pharma, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Foundation for Sarcoidosis Research
- Responsible party
- Sponsor
- Investigators
- Gennyne Walker, Study director, aTyr Pharma, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03824392
- Sponsor's protocol ID
- ATYR1923-C-002
- Status last verified
- Jun 2023
- First submitted
- 28 Jan 2019
- Last updated
- 18 Jul 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Walker G, Adams R, Guy L, Chandrasekaran A, Kinnersley N, Ramesh P, Zhang L, Brown F, Niranjan V. Exposure-response analyses of efzofitimod in patients with pulmonary sarcoidosis. Front Pharmacol. 2023 Oct 3;14:1258236. doi: 10.3389/fphar.2023.1258236. eCollection 2023.
PubMed 37854715Culver DA, Aryal S, Barney J, Hsia CCW, James WE, Maier LA, Marts LT, Obi ON, Sporn PHS, Sweiss NJ, Shukla S, Kinnersley N, Walker G, Baughman R. Efzofitimod for the Treatment of Pulmonary Sarcoidosis. Chest. 2023 Apr;163(4):881-890. doi: 10.1016/j.chest.2022.10.037. Epub 2022 Nov 8.
PubMed 36356657
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled Multiple Ascending Dose Study of Intravenous ATYR1923 in Patients With Pulmonary Sarcoidosis
- ClinicalTrials.gov ID
- NCT03824392
- Acronym / sponsor ID
- ATYR1923-C-002
- Conditions
- Pulmonary Sarcoidosis
- Keywords
- Pulmonary Sarcoidosis, Resokine, Sarcoidosis, Granulomas, Inflammation, Lymphoproliferative Disorders, Interstitial Lung Disease, Neuropilin-2
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- aTyr Pharma, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Foundation for Sarcoidosis Research
- Study start
- 29 Jan 2019 (actual)
- Primary completion
- 29 Jun 2021 (actual)
- Study completion
- 29 Jun 2021 (actual)
- First posted
- 31 Jan 2019 (actual)
- Results
- Posted 18 Jul 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- 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
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Biological: Efzofitimod 1.0 mg/kg or Placebo, Biological: Efzofitimod 3.0 mg/kg or Placebo, Biological: Efzofitimod 5.0 mg/kg or PlaceboParticipants will receive placebo matched to efzofitimod via intravenous (IV) infusion every 4 weeks until Week 20. |
| Efzofitimod 1.0 mg/kg | Experimental | Biological: Efzofitimod 1.0 mg/kg or PlaceboParticipants will receive efzofitimod 1.0 milligrams/kilogram (mg/kg) via IV infusion every 4 weeks until Week 20. |
| Efzofitimod 3.0 mg/kg | Experimental | Biological: Efzofitimod 3.0 mg/kg or PlaceboParticipants will receive efzofitimod 3.0 mg/kg via IV infusion every 4 weeks until Week 20. |
| Efzofitimod 5.0 mg/kg | Experimental | Biological: Efzofitimod 5.0 mg/kg or PlaceboParticipants will receive efzofitimod 5.0 mg/kg via IV infusion every 4 weeks until Week 20. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Diagnosis of pulmonary sarcoidosis for ≥6 months (cutaneous and ocular involvement allowed), defined as:
- Must have symptomatic and/or active pulmonary sarcoidosis as evidenced by:
- 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 (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Efzofitimod 1.0 mg/kg or PlaceboParticipants to receive efzofitimod 1.0 mg/kg IV every 4 weeks or placebo matched to efzofitimod every 4 weeks | Biological | Efzofitimod 1.0 mg/kg, Placebo |
| Efzofitimod 3.0 mg/kg or PlaceboParticipants to receive efzofitimod 3.0 mg/kg IV every 4 weeks or placebo matched to efzofitimod every 4 weeks | Biological | Efzofitimod 3.0 mg/kg, Placebo |
| Efzofitimod 5.0 mg/kg or PlaceboParticipants to receive efzofitimod 5.0 mg/kg IV every 4 weeks or placebo matched to efzofitimod every 4 weeks | Biological | Efzofitimod 5.0 mg/kg, Placebo |
Primary outcome
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: Baseline up to Week 24
An AE was any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. TEAEs were defined as any adverse event or worsening of an existing condition after initiation of the investigational product and through 30 days after the participant's last study visit (study completion or early termination). SAEs included death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'.
4 secondary outcomes
Time-adjusted Area Under the Curve (AUC) of Background Oral Corticosteroid (OCS) Usage Over Study Period
Time frame: Baseline up to Week 24 (Day 1 to End of Dosing Period)
Number of Participants Who Achieved and Maintained The Targeted Tapered Dose of Prednisone 5 mg/Day (or Equivalent)
Time frame: Baseline up to Week 24
Number of Participants With Positive Anti-Drug Antibodies (Anti-Efzofitimod)
Time frame: Baseline up to Week 24
Number of Participants With at Least One Positive Anti-Jo-1 Antibodies Titers
Time frame: Baseline up to Week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37854715Walker G, Adams R, Guy L, Chandrasekaran A, Kinnersley N, Ramesh P, Zhang L, Brown F, Niranjan V. Exposure-response analyses of efzofitimod in patients with pulmonary sarcoidosis. Front Pharmacol. 2023 Oct 3;14:1258236. doi: 10.3389/fphar.2023.1258236. eCollection 2023.
- Derived from this study: PubMed 36356657Culver DA, Aryal S, Barney J, Hsia CCW, James WE, Maier LA, Marts LT, Obi ON, Sporn PHS, Sweiss NJ, Shukla S, Kinnersley N, Walker G, Baughman R. Efzofitimod for the Treatment of Pulmonary Sarcoidosis. Chest. 2023 Apr;163(4):881-890. doi: 10.1016/j.chest.2022.10.037. Epub 2022 Nov 8.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gennyne Walker study director
aTyr Pharma, Inc.
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study of Pulmonary Sarcoidosis, run by aTyr Pharma, Inc. at 15 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) (time frame: Baseline up to Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03824392, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jul 2023.