Trial Review

Technical difficulties have been reported by some users of the search function and is being investigated by technical staff. Thank you for your patience and apologies for any inconvenience caused.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05032066




Registration number
NCT05032066
Ethics application status
Date submitted
27/08/2021
Date registered
2/09/2021
Date last updated
3/05/2024

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
1/07/2025
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
State/province [4] 0 0
Kansas
Country [5] 0 0
United States of America
State/province [5] 0 0
Nebraska
Country [6] 0 0
United States of America
State/province [6] 0 0
New Hampshire
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
South Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Tennessee
Country [13] 0 0
United States of America
State/province [13] 0 0
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
State/province [16] 0 0
Tucumán
Country [17] 0 0
Argentina
State/province [17] 0 0
Ciudad de Buenos Aires
Country [18] 0 0
Argentina
State/province [18] 0 0
Santa Fe
Country [19] 0 0
Canada
State/province [19] 0 0
Ontario
Country [20] 0 0
Chile
State/province [20] 0 0
Maule
Country [21] 0 0
Chile
State/province [21] 0 0
Región-MetropolitanadeSantiago
Country [22] 0 0
Chile
State/province [22] 0 0
Valparaíso
Country [23] 0 0
Chile
State/province [23] 0 0
Talca
Country [24] 0 0
Chile
State/province [24] 0 0
Valdivia
Country [25] 0 0
France
State/province [25] 0 0
Bouches-du-Rhône
Country [26] 0 0
France
State/province [26] 0 0
Gironde
Country [27] 0 0
France
State/province [27] 0 0
Indre-et-Loire
Country [28] 0 0
Germany
State/province [28] 0 0
Nordrhein-Westfalen
Country [29] 0 0
Greece
State/province [29] 0 0
Achaïa
Country [30] 0 0
Greece
State/province [30] 0 0
Attiki
Country [31] 0 0
Greece
State/province [31] 0 0
Ioannina
Country [32] 0 0
Greece
State/province [32] 0 0
Iraklio
Country [33] 0 0
Greece
State/province [33] 0 0
Larisa
Country [34] 0 0
Italy
State/province [34] 0 0
Emilia-Romagna
Country [35] 0 0
Italy
State/province [35] 0 0
Siena
Country [36] 0 0
Japan
State/province [36] 0 0
Hyôgo
Country [37] 0 0
Japan
State/province [37] 0 0
Ibaraki
Country [38] 0 0
Japan
State/province [38] 0 0
Kanagawa
Country [39] 0 0
Japan
State/province [39] 0 0
Hiroshima
Country [40] 0 0
Japan
State/province [40] 0 0
Tokyo
Country [41] 0 0
Japan
State/province [41] 0 0
Ôsaka
Country [42] 0 0
Korea, Republic of
State/province [42] 0 0
Gyeonggido
Country [43] 0 0
Korea, Republic of
State/province [43] 0 0
Seoul
Country [44] 0 0
Mexico
State/province [44] 0 0
Jalisco
Country [45] 0 0
Mexico
State/province [45] 0 0
Nuevo León
Country [46] 0 0
Mexico
State/province [46] 0 0
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
State/province [52] 0 0
Western Cape
Country [53] 0 0
Spain
State/province [53] 0 0
Barcelona
Country [54] 0 0
Spain
State/province [54] 0 0
Madrid
Country [55] 0 0
Taiwan
State/province [55] 0 0
Kaohsiung City
Country [56] 0 0
Taiwan
State/province [56] 0 0
Taichung
Country [57] 0 0
Taiwan
State/province [57] 0 0
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
HZNP-HZN-825-303 (HARBOR) comprises of 2 parts. Part 1 (Core Phase) is a randomized,
double-blind, placebo-controlled, repeat-dose, multicenter trial to evaluate the efficacy,
safety and tolerability of HZN-825 in participants with Idiopathic Pulmonary Fibrosis (IPF).

Part 2 (Extension Phase) is an optional, open-label, repeat-dose, multicenter extension of
the Core Phase. The trial will include up to an 8-week Screening Period and a 52-week
Double-blind Treatment Period in the Core Phase and 52 weeks of open-label HZN-825 treatment
in the Extension Phase.

During the Core Phase, participants will be screened within 8 weeks prior to the baseline
(Day 1) Visit. Approximately 135 participants who meet the trial eligibility criteria will be
randomly assigned in a 1:1:1 ratio on Day 1 to receive HZN-825 300 mg QD, HZN-825 300 mg BID
or matching placebo orally for 52 weeks using the following 2 stratification factors:

1. Concomitant use of approved IPF therapy (i.e., nintedanib or pirfenidone): yes or no

2. Forced vital capacity (FVC) % predicted at Baseline: =70% or <70%

Participants who complete the 52-week Double blind Treatment Period of the Core Phase of the
trial will be invited to extend their participation in the 52-week Extension Phase of the
trial.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05032066
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