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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05032066




Registration number
NCT05032066
Ethics application status
Date submitted
27/08/2021
Date registered
2/09/2021

Titles & IDs
Public title
A Multicenter Trial to Evaluate the Efficacy, Safety and Tolerability of HZN-825 in Subjects With Idiopathic Pulmonary Fibrosis
Scientific title
A Phase 2b Randomized, Double-blind, Placebo-controlled, Repeat-dose, Multicenter Trial to Evaluate the Efficacy, Safety and Tolerability of HZN-825 in Subjects With Idiopathic Pulmonary Fibrosis
Secondary ID [1] 0 0
2021-001253-32
Secondary ID [2] 0 0
HZNP-HZN-825-303
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Idiopathic Pulmonary Fibrosis 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - HZN-825
Treatment: Drugs - Placebo

Experimental: HZN-825 300 mg once daily (QD) - Two 150 mg oral tablets given in the morning with a meal and two matching placebo tablets given in the evening with a meal; total daily dose 300 mg HZN-825.

Experimental: HZN-825-300 mg twice daily (BID) - Two 150 mg oral tablets given in the morning with a meal and two 150 mg oral tablets given in the evening with a meal; total daily dose 600 mg HZN-825.

Placebo comparator: Placebo BID - Matching placebo tablets (2) given in the morning with a meal and matching placebo tablets (2) given in the evening with a meal; total dose 4 placebo tablets.


Treatment: Drugs: HZN-825
Core Phase: Participants will receive HZN-825 300 mg QD, HZN-825 300 mg BID or matching placebo orally in the morning and evening with a meal for 52 weeks according to randomization schema.

Extension Phase: Participants will receive open-label HZN-825 150 mg orally in the morning and evening with a meal for 52 weeks.

Treatment: Drugs: Placebo
Core Phase: Participants will receive HZN-825 300 mg QD, HZN-825 300 mg BID or matching placebo orally in the morning and evening with a meal for 52 weeks according to randomization schema.

Extension Phase: Participants who received matching placebo in the Core Phase will receive open-label HZN-825 150 mg orally in the morning and evening with a meal for 52 weeks.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Core Phase: Change in Forced Vital Capacity (FVC) percent (FVC %) predicted from Baseline to Week 52
Timepoint [1] 0 0
Baseline to Week 52
Primary outcome [2] 0 0
Extension Phase: Change from the Open Label Extension (OLE) baseline, defined as the latest measurement prior to the first dose of HZN-825 in the extension phase in FVC % predicted from Baseline to Week 104
Timepoint [2] 0 0
Baseline to Week 104
Primary outcome [3] 0 0
Extension Phase: Change from the HZN-825 baseline, defined as the latest measurement prior to the first dose of HZN-825 in either the core phase or the extension phase in FVC % predicted from Baseline to Week 104
Timepoint [3] 0 0
Baseline to Week 104
Secondary outcome [1] 0 0
Core Phase: Change from baseline in the 6MWT (Six-Minute Walk Test) results to Week 52
Timepoint [1] 0 0
Baseline to Week 52
Secondary outcome [2] 0 0
Core Phase: Change from baseline in K-BILD (King's Brief Interstitial Lung Disease) scores to Week 52
Timepoint [2] 0 0
Baseline to Week 52
Secondary outcome [3] 0 0
Core Phase: Change from baseline in L-IPF (Living with IPF[Idiopathic Pulmonary Fibrosis]) scores to Week 52
Timepoint [3] 0 0
Baseline to Week 52
Secondary outcome [4] 0 0
Core Phase: Change from baseline in LCQ (Leicester Cough Questionnaire) scores to Week 52
Timepoint [4] 0 0
Baseline to Week 52
Secondary outcome [5] 0 0
Core Phase: Time to first hospitalization due to respiratory distress up to Week 52
Timepoint [5] 0 0
Baseline to Week 52
Secondary outcome [6] 0 0
Core Phase: Time to first onset of the composite endpoint of PFS (progression-free survival) from Baseline up to Week 52, where progression includes decline in FVC % predicted =10% or death
Timepoint [6] 0 0
Baseline to Week 52
Secondary outcome [7] 0 0
Core Phase: Incidence of treatment emergent adverse events (TEAEs)
Timepoint [7] 0 0
Day 1 to Week 52
Secondary outcome [8] 0 0
Core Phase: Incidence of serous adverse events (SAEs)
Timepoint [8] 0 0
Day 1 to Week 52
Secondary outcome [9] 0 0
Core Phase: Incidence of adverse events of special interest (AESIs): orthostatic hypotension
Timepoint [9] 0 0
Day 1 to Week 52
Secondary outcome [10] 0 0
Core Phase: Incidence and frequency of use of concomitant medication(s)
Timepoint [10] 0 0
Day 1 to Week 52
Secondary outcome [11] 0 0
Core Phase: Change in abnormal and clinically significant vital signs as reported as TEAEs
Timepoint [11] 0 0
Day 1 to Week 52
Secondary outcome [12] 0 0
Core Phase: Change in abnormal clinical safety laboratory test results as reported as TEAEs
Timepoint [12] 0 0
Day 1 to Week 52
Secondary outcome [13] 0 0
Core Phase: Change in abnormal and clinically significant 12-lead electrocardiogram (ECG) or echocardiogram measurements as reported as TEAEs.
Timepoint [13] 0 0
Day 1 to Week 52
Secondary outcome [14] 0 0
Extension Phase: Incidence of AESIs: orthostatic hypotension
Timepoint [14] 0 0
Day 1 to Week 104
Secondary outcome [15] 0 0
Extension Phase: Incidence of TEAEs
Timepoint [15] 0 0
Day 1 to Week 104
Secondary outcome [16] 0 0
Extension Phase: Incidence and frequency of use of concomitant medication(s)
Timepoint [16] 0 0
Baseline to Week 104
Secondary outcome [17] 0 0
Extension Phase: Change from trial baseline in abnormal and clinically significant vital signs reported as TEAEs
Timepoint [17] 0 0
Baseline to Week 104
Secondary outcome [18] 0 0
Extension Phase: Change from trial baseline in abnormal and clinically significant 12-lead ECG) measurements as reported as TEAEs.
Timepoint [18] 0 0
Baseline to Week 104
Secondary outcome [19] 0 0
Extension Phase: Change from trial baseline in abnormal clinical safety laboratory test results as reported as TEAEs
Timepoint [19] 0 0
Baseline to Week 104

Eligibility
Key inclusion criteria
Key Inclusion Criteria in Core Phase:

1. Male or female =18 years of age at Screening.
2. Current diagnosis of IPF, as defined by American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Society (ALAT) guidelines and determined by central review; the date of initial diagnosis of IPF should be =7 years prior to Screening.
3. No recent changes or planned changes to the dose or regimen for IPF therapy, defined as:

* Receiving a stable dose of IPF-approved therapy (i.e., nintedanib or pirfenidone) for a minimum of 3 months prior to Day 1 with no plans to change the background regimen during trial participation, or
* Not currently receiving background IPF-approved therapy at Screening (either naïve to IPF-approved therapy or previously discontinued any IPF-approved therapy at least 4 weeks prior to Day 1 or drug-specific, 5 half-lives elimination period if longer than 4 weeks), and with no current plans to restart treatment during trial participation
* Participants receiving any additional agent for IPF therapy must be on a stable regimen for at least 3 months prior to Day 1 with no current plans to change the treatment regimen during trial participation. Any previously discontinued therapy used to treat IPF must have been discontinued at least 4 weeks prior to Day 1 or 5 half-lives for that specific therapy must have elapsed, whichever is longer, with no plans to restart the therapy during trial participation.
4. Lung high-resolution computed tomography (HRCT) historically performed within 6 months prior to the Screening Visit and according to the minimum requirements for IPF diagnosis by central review based on participant's HRCT. If an evaluable HRCT is not available within 6 months prior to Screening, an HRCT will be performed at Screening to determine eligibility, according to the same requirements as the historical HRCT.
5. HRCT shows =10% to <50% parenchymal fibrosis (reticulation) and the extent of fibrotic changes is greater than the extent of emphysema on the most recent HRCT scan (central reviewer determined).
6. Meets all of the following criteria during the Screening Period:

1. FVC =45% predicted of normal
2. forced expiratory volume in 1 second (FEV1)/FVC =0.7
3. Diffusing capacity of the lungs for carbon monoxide (DLCO) corrected for hemoglobin is =25% and =90% predicted of normal
7. Estimated minimum life expectancy of =30 months for non-IPF-related disease, in the opinion of the Investigator.
8. Vaccinations are up to date given age, comorbidities and local availability prior to trial drug dosing.
9. Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the trial.

Key Inclusion Criteria in Extension Phase:

1. Completed the Double-blind Treatment Period (Week 52) of the Core Phase of the trial; subjects prematurely discontinued from trial drug in the Core Phase of the trial for reasons other than safety or tolerability may be included at the discretion of the Investigator after completing scheduled visits, including Week 52 assessments.
2. Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the Extension Phase of the trial.

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria Core Phase:

1. Any of the following cardiovascular diseases:

1. uncontrolled, severe hypertension (=160/100 mmHg), within 6 months of Screening
2. myocardial infarction within 6 months of Screening
3. unstable cardiac angina within 6 months of Screening
2. Interstitial lung disease (ILD) associated with known primary diseases (e.g., sarcoidosis, amyloidosis and coronavirus disease 2019 [COVID-19]), connective tissue disorders (e.g., rheumatoid arthritis, systemic lupus erythematosus, Sjogren's, dermatomyositis, scleroderma), exposures (e.g., radiation, silica, asbestos and coal dust) or drugs (e.g., amiodarone).
3. Known active bacterial, viral, fungal, mycobacterial or other infection, including tuberculosis or atypical mycobacterial disease (fungal infections of nail beds are allowed). The participant must be 3 months beyond any acute infection with COVID-19 if there has been a prior infection.
4. Clinically significant pulmonary hypertension requiring chronic medical therapy.
5. Use of any of the following therapies within 4 weeks prior to Screening, during the Screening Period or planned during the trial: prednisone at steady dose >10 mg/day or equivalent or cyclosporine. Change in regimen or dosage of any immunosuppressant during the Screening Period through the end of trial participation will require consultation with and approval by the trial Medical Monitor.
6. Use of rifampin within 2 weeks prior to Day 1 or planned during the trial.
7. Malignant condition in the past 5 years (except successfully treated basal/squamous cell carcinoma of the skin or cervical cancer in situ).
8. Women of childbearing potential (WOCBP) or male subjects not agreeing to use highly effective method(s) of birth control throughout the trial and for 4 weeks after last dose of trial drug. Females must refrain from egg/ova donation for 4 weeks after the last dose of trial drug and males must refrain from sperm donation for 3 months after the last dose of trial drug.
9. Pregnant or lactating women and women who plan to become pregnant or breast feed during the trial and within 4 weeks after the last dose of trial drug.
10. Current drug or alcohol abuse or history of either within the previous 2 years, in the opinion of the Investigator or as reported by the subject.
11. Previous enrollment in this trial or participation in a prior HZN-825 or SAR100842 clinical trial.
12. Known history of positive test for human immunodeficiency virus (HIV).
13. Active hepatitis (hepatitis B: positive hepatitis B surface antigen and positive anti-hepatitis B core antibody [anti-HBcAb] and negative hepatitis B surface antibody [HBsAb] or positive for HBcAb with a positive test for HBsAb and with presence of hepatitis B virus DNA at Screening; hepatitis C: positive anti-hepatitis C virus [anti-HCV] and positive RNA HCV).
14. Current alcoholic liver disease, primary biliary cirrhosis or primary sclerosing cholangitis.
15. Previous organ transplant (including allogeneic and autologous marrow transplant).
16. International normalized ratio >2, prolonged prothrombin time >1.5 × the upper limit of normal (ULN) or partial thromboplastin time >1.5 × ULN at Screening.
17. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.0 × ULN.
18. Estimated glomerular filtration rate <30 mL/min/1.73 m^2 at Screening.
19. Total bilirubin >1.5 × ULN. Subjects with documented diagnosis of Gilbert's syndrome may be enrolled if their total bilirubin is =3.0 mg/dL.
20. Moderate (Child-Pugh B) to severe (Child-Pugh C) hepatic impairment according to the Child-Pugh scoring system.
21. Any confirmed Grade 3 or higher laboratory abnormality.
22. Any laboratory abnormality at Screening that, in the opinion of the Investigator, would preclude the participant's entry in the trial.
23. Exposure to an experimental drug (with the exception of HZN-825) or experimental vaccine within either 30 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is the longest, prior to Day 1.
24. Any other condition that, in the opinion of the Investigator, would preclude enrollment in the trial.

Key Exclusion Criteria Extension Phase:

1. Anticipated use of another investigational agent for any condition during the course of the trial.
2. New diagnosis of malignant condition after enrolling in Trial HZNP-HZN-825-303 (except successfully treated basal/squamous cell carcinoma of the skin or cervical cancer in situ).
3. Estimated minimum life expectancy =18 months, in the opinion of the Investigator.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
25/08/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/07/2025
Actual
Sample size
Target
Accrual to date
Final
153
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
Box Hill Hospital - Box Hill
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
3128 - Box Hill
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
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Kansas
Country [5] 0 0
United States of America
State/province [5] 0 0
Nebraska
Country [6] 0 0
United States of America
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New Hampshire
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United States of America
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New York
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United States of America
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North Carolina
Country [9] 0 0
United States of America
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Ohio
Country [10] 0 0
United States of America
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Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
South Carolina
Country [12] 0 0
United States of America
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Tennessee
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United States of America
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Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Wisconsin
Country [15] 0 0
Argentina
State/province [15] 0 0
Buenos Aires
Country [16] 0 0
Argentina
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Tucumán
Country [17] 0 0
Argentina
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Ciudad de Buenos Aires
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Argentina
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Santa Fe
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Canada
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Ontario
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Chile
State/province [20] 0 0
Maule
Country [21] 0 0
Chile
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Región-MetropolitanadeSantiago
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Chile
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Valparaíso
Country [23] 0 0
Chile
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Talca
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Chile
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Valdivia
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France
State/province [25] 0 0
Bouches-du-Rhône
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France
State/province [26] 0 0
Gironde
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France
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Indre-et-Loire
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Germany
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Nordrhein-Westfalen
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Greece
State/province [29] 0 0
Achaïa
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Greece
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Attiki
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Greece
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Ioannina
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Greece
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Iraklio
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Greece
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Larisa
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Italy
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Emilia-Romagna
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Italy
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Siena
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Japan
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Hyôgo
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Japan
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Ibaraki
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Japan
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Kanagawa
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Japan
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Hiroshima
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Japan
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Tokyo
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Japan
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Ôsaka
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Korea, Republic of
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Gyeonggido
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Korea, Republic of
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Seoul
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Mexico
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Jalisco
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Mexico
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Nuevo León
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Mexico
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Oaxaca
Country [47] 0 0
Netherlands
State/province [47] 0 0
Rotterdam
Country [48] 0 0
Poland
State/province [48] 0 0
Pomorskie
Country [49] 0 0
Poland
State/province [49] 0 0
Slaskie
Country [50] 0 0
Poland
State/province [50] 0 0
Kraków
Country [51] 0 0
South Africa
State/province [51] 0 0
Kwazulu - Natal
Country [52] 0 0
South Africa
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Western Cape
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Spain
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Barcelona
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Spain
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Madrid
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Taiwan
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Kaohsiung City
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Taiwan
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Taichung
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Taiwan
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Taipei
Country [58] 0 0
Turkey
State/province [58] 0 0
Kocaeli
Country [59] 0 0
United Kingdom
State/province [59] 0 0
Liverpool

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05032066