A Multicenter Trial to Evaluate the Efficacy, Safety and Tolerability of HZN-825 in Subjects With Idiopathic Pulmonary Fibrosis

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

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.

Study Overview

• Status: Terminated
• Conditions: Idiopathic Pulmonary Fibrosis
• Intervention / Treatment: Drug: HZN-825; Drug: Placebo

Detailed Description

Part 1 (Core Phase) The overall objective of the Core Phase is to investigate the efficacy, safety and tolerability of 2 dose regimens of HZN-825, a selective antagonist of lysophosphatidic acid receptor-1 (LPAR1), administered orally once daily (QD) or twice daily (BID) for 52 weeks in the treatment of participants with IPF.

Part 2 (Extension Phase) The overall objective of the Extension Phase is to investigate the long-term efficacy, safety and tolerability of HZN-825, a selective antagonist of LPAR1, administered at a dose of 300 mg BID orally to participants with IPF in a 52-week open-label extension (OLE) following completion of the Core Phase of the trial. The dose for the Extension Phase may be modified based on the results of the Core Phase.

Two types of Baseline are defined for the Extension Phase:

• OLE Baseline, defined as the latest measurement prior to the first dose of HZN-825 in the Extension Phase
• 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. For subjects who received placebo in the Core Phase, OLE Baseline will be the same as HZN-825 Baseline.

Acquired from Horizon in 2024

• Study Type: Interventional
• Enrollment (Actual): 153
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Ciudad de Buenos Aires, Argentina, C1426ABP
    • Centro Médico Dra de Salvo
  • Santa Fe, Argentina, 3000
    • Instituto Del Buen Aire
  • Buenos Aires
    • Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1013AAB
      • Stat Research S.A.
    • Mar del Plata, Buenos Aires, Argentina, 7600
      • Instituto Ave Pulmo
    • San Juan Bautista, Buenos Aires, Argentina, 1888
      • Instituto De Enfermedades Respiratorias E Investigacion Medica
  • Tucumán Province
    • San Miguel de Tucumán, Tucumán Province, Argentina, 4000
      • Instituto De Patologias Respiratorias
• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Box Hill Hospital
• Canada
  • Ontario
    • Ajax, Ontario, Canada, L1S 2J5
      • Dynamic Drug Advancement Ltd.
    • Hamilton, Ontario, Canada, L8N 4A6
      • St. Joseph's Healthcare Hamilton
• Chile
  • Talca, Chile, 3465586
    • Centro de Investigación del Maule
  • Valdivia, Chile, 8330033
    • Clinical Research Chile SpA
  • Maule Region
    • Curicó, Maule Region, Chile, 3440000
      • Centro de Investigacion Curico
  • Región de Valparaíso
    • Quillota, Región de Valparaíso, Chile, 2260000
      • Centro Respiratorio Integral LTDA. (CENRESIN)
  • Región-MetropolitanadeSantiago
    • Las Condes, Región-MetropolitanadeSantiago, Chile, 7550000
      • Universidad De Los Andes
    • Providencia, Región-MetropolitanadeSantiago, Chile, 7500587
      • Enroll SpA
    • Santiago, Región-MetropolitanadeSantiago, Chile, 8330008
      • Meditek Ltda
    • Ñuñoa, Región-MetropolitanadeSantiago, Chile, 7750495
      • MIRES/MYF estudios cli-nicos
• France
  • Bouches-du-Rhône
    • Marseille, Bouches-du-Rhône, France, 13915
      • Hopital Nord AP-HM
  • Gironde
    • Pessac, Gironde, France, 33604
      • Hopital Haut Leveque
  • Indre-et-Loire
    • Tours, Indre-et-Loire, France, 37044
      • Hopital Bretonneau
• Germany
  • North Rhine-Westphalia
    • Hemer, North Rhine-Westphalia, Germany, 58675
      • Lungenklinik Hemer
• Greece
  • Heraklion, Greece, 711 10
    • University General Hospital of Heraklion
  • Ioannina, Greece, 455 00
    • University General Hospital of Ioannina
  • Larissa, Greece, 411 10
    • University General Hospital of Larissa
  • Achaïa
    • Pátrai, Achaïa, Greece, 265 04
      • University General Hospital of Patras
  • Attica
    • Athens, Attica, Greece, 10676
      • Evangelismos General Hospital of Athens
    • Marousi, Attica, Greece, 151 25
      • Athens Medical Center
• Italy
  • Siena, Italy, 53100
    • Azienda Ospedaliera Universitaria Senese
  • Emilia-Romagna
    • Forlì, Emilia-Romagna, Italy, 47121
      • Presidio Ospedaliero GB Morgagni L Pierantoni
• Japan
  • Hiroshima, Japan, 734-0004
    • Hiroshima Prefectural Hospital
  • Tokyo, Japan, 113-8519
    • Medical Hospital of Tokyo Medical and Dental University
  • Hyôgo
    • Himeji-Shi, Hyôgo, Japan, 670-8520
      • National Hospital Organization Himeji Medical Center
  • Ibaraki
    • Naka-Gun, Ibaraki, Japan, 319-1113
      • National Hospital Organization Ibarakihigashi National Hospital
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 235-0041
      • Kanagawa Cardiovascular and Respiratory Center
  • Ôsaka
    • Sakaishi, Ôsaka, Japan, 591-8025
      • National Hospital Organization Kinki-Chuo Chest Medical Center
• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44160
      • CICUM San Miguel
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64460
      • Hospital Universitario Dr. Jose Eleuterio Gonzalez
    • Monterrey, Nuevo León, Mexico, 64718
      • Unidad de Investigación Clínica En Medicina SC
  • Oaxaca
    • Centro, Oaxaca, Mexico, 68000
      • Oaxaca Site Management Organization (OSMO)
• Netherlands
  • Rotterdam, Netherlands, 3015 GD
    • Erasmus MC
• Poland
  • Krakow, Poland, 30-510
    • MCM Krakow - PRATIA - PPDS
  • Pomeranian Voivodeship
    • Gdansk, Pomeranian Voivodeship, Poland
      • Uniwersyteckie Centrum Kliniczne
  • Silesian Voivodeship
    • Katowice, Silesian Voivodeship, Poland, 40-752
      • PULMAG Grzegorz Gasior Marzena Kociolek Spolka Cywilna
• South Africa
  • KwaZulu-Natal
    • Durban, KwaZulu-Natal, South Africa, 4091
      • KwaPhila Health Solutions
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7700
      • University of Cape Town Lung Institute (UCTLI)
    • Cape Town, Western Cape, South Africa, 7764
      • Dr. Ismail Abdullah Private Practice
• South Korea
  • Seoul, South Korea
    • Samsung Medical Center
  • Seoul, South Korea, 02841
    • Korea University Anam Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center-PPDS
  • Gyeonggido
    • Seongnam-si, Gyeonggido, South Korea, 13620
      • Seoul National University Bundang Hospital
• Spain
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Hospital Universitario de Bellvitge
  • Madrid
    • Pozuelo de Alarcón, Madrid, Spain, 28223
      • Hospital Universitario Quironsalud Madrid
• Taiwan
  • Kaohsiung City, Taiwan, 807
    • Kaohsiung Medical University - Chung-Ho Memorial Hospital
  • Taichung, Taiwan, 404
    • China Medical University Hospital - PPDS
  • Taipei, Taiwan
    • Taipei Veterans General Hospital
  • Taipei, Taiwan, 220
    • Far Eastern Memorial Hospital
• Turkey (Türkiye)
  • Kocaeli, Turkey (Türkiye), 41380
    • Kocaeli University Hospital
• United Kingdom
  • Liverpool, United Kingdom, L9 7AL
    • Connolly Hospital Blanchardstown
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • California
    • Palm Springs, California, United States, 92262
      • Palmtree Clinical Research
  • Florida
    • Clearwater, Florida, United States, 33765
      • St. Francis Medical Institute
    • Orlando, Florida, United States, 32803
      • Central Florida Pulmonary Group PA
    • Tamarac, Florida, United States, 33321
      • DBC Research Corp.
    • Tampa, Florida, United States, 33609
      • GCP Clinical Research
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Nebraska Pulmonary Specialties LLC
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756-1000
      • Dartmouth Hitchcock Medical Center
  • New York
    • Commack, New York, United States, 11725
      • Stony Brook Medicine Advanced Specialty Care
  • North Carolina
    • Gastonia, North Carolina, United States, 28054
      • Clinical Research of Gastonia
    • Shelby, North Carolina, United States, 28150
      • Shelby Clinical Research
    • Winston-Salem, North Carolina, United States, 27103
      • Southeastern Research Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Philadelphia, Pennsylvania, United States, 19140-5103
      • Temple University Hospital
  • South Carolina
    • Rock Hill, South Carolina, United States, 29732
      • Clinical Research of Rock Hill
  • Tennessee
    • Franklin, Tennessee, United States, 37067
      • Clinical Trials Center of Middle Tennessee
    • Nashville, Tennessee, United States, 37204
      • Vanderbilt University Medical Center
  • Texas
    • El Paso, Texas, United States, 79902-1124
      • El Paso Pulmonary Association - Elligo
    • McKinney, Texas, United States, 75069
      • Metroplex Pulmonary and Sleep Medicine Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226-3522
      • Northwestern Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: 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.
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.	Drug: 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.
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.	Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Core Phase: Change in FVC % Predicted From Baseline to Week 52	FVC was assessed using a blowing device provided by the Sponsor. The best of 3 efforts was defined as the highest FVC, obtained on any of the 3 blows meeting the ATS/ERS criteria with a maximum of 8 maneuvers. FVC % predicted was calculated by taking the observed FVC measurement and dividing it by a predicted value multiplied by 100 (% FVC predicted = (FVC observed/FVC predicted) x 100). The predicted value is an average of the normal FVC volume for a person of the same sex, ethnicity, age and height.	Baseline and Week 52
Extension Phase: Change in FVC % Predicted From OLE Baseline to Week 104	OLE baseline was defined as the latest measurement prior to the first dose of HZN-825 in the extension phase. FVC was assessed using a blowing device provided by the Sponsor. The best of 3 efforts was defined as the highest FVC, obtained on any of the 3 blows meeting the ATS/ERS criteria with a maximum of 8 maneuvers. FVC % predicted was calculated by taking the observed FVC measurement and dividing it by a predicted value multiplied by 100 (% FVC predicted = (FVC observed/FVC predicted) x 100). The predicted value is an average of the normal FVC volume for a person of the same sex, ethnicity, age and height.	OLE baseline (Week 52) and Week 104

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Core Phase: Number of Participants With a Decline in FVC % Predicted ≥10% From Baseline at Week 52	FVC was assessed using a blowing device provided by the Sponsor. The best of 3 efforts was defined as the highest FVC, obtained on any of the 3 blows meeting the ATS/ERS criteria with a maximum of 8 maneuvers. FVC % predicted was calculated by taking the observed FVC measurement and dividing it by a predicted value multiplied by 100 (% FVC predicted = (FVC observed/FVC predicted) x 100). The predicted value is an average of the normal FVC volume for a person of the same sex, ethnicity, age and height.	Baseline and Week 52
Core Phase: Change in the 6-Minute Walk Test (6MWT) Results From Baseline to Week 52	The 6MWT measures the distance a subject can quickly walk on a flat, hard surface in 6 minutes (6-minute walk distance). This test evaluates the global and integrated responses of all the systems involved during exercise, including the pulmonary and cardiovascular systems, systemic circulation, peripheral circulation, blood, neuromuscular units and muscle metabolism.	Baseline and Week 52
Core Phase: Change in King's Brief Interstitial Lung Disease (K-BILD) Questionnaire Scores From Baseline to Week 52	The K-BILD is a self-completed health status questionnaire comprising 15 items and a 7-point Likert response scale that was developed and validated specifically for patients with IPF. This questionnaire has 3 domains: psychological, breathlessness and activities and chest symptoms. The K-BILD domains and total score range from 0 to 100; 100 represents best health status. A positive change from baseline indicates an improvement in symptoms.	Baseline and Week 52
Core Phase: Change in Living With IPF (L-IPF) Scores From Baseline to Week 52	The L-IPF is a validated questionnaire that assesses symptoms, disease impacts and health-related quality of life in subjects with IPF. This questionnaire was developed with input from the FDA and comprises 2 modules: a 15-item symptom module with 3 domains (dyspnea, cough, and energy), all with a 24-hour recall, and a 20-item impacts module with 1-week recall. Symptoms Total Score and Impacts Total Score were transformed to a model-based scale ranging from 0 to 100 where higher scores indicate greater impairment.	Baseline and Week 52
Core Phase: Change in Leicester Cough Questionnaire (LCQ) Scores From Baseline to Week 52	The LCQ is a patient-reported questionnaire evaluating the impact of cough on quality of life. The LCQ comprises 19 items and takes 5 to 10 minutes to complete. Each item assesses symptoms or the impact of symptoms over the last 2 weeks on a 7-point Likert scale. Scores in 3 domains (physical, psychological, and social) are calculated as a mean for each domain (range: 1 to 7). A total score (range: 3 to 21) is also calculated by adding together the domain scores. Higher scores indicate better quality of life and a positive change from baseline indicates an improvement in quality of life.	Baseline to Week 52
Core Phase: Time to First Hospitalization Due to Respiratory Distress From Baseline up to Week 52	Hospitalization due to respiratory distress was defined as a non-elective hospitalization lasting more than 24 hours in a hospital, emergency room or observation unit, due to respiratory causes that occur after randomization Adverse events identified as leading to hospitalization due to respiratory distress were adjudicated to confirm that the event and hospitalization met the stated criteria. Participants who did not experience a hospitilization event were considered censored.	Up to Week 52
Core Phase: Time to First Onset of the Composite Endpoint of Progression-Free Survival (PFS) From Baseline up to Week 52	The time-to-progression was defined as the duration from the date of first dose of study drug to either (a) the date of the visit where FVC % predicted declines ≥ 10% from Baseline or (b) the date of participant death, whichever occurred earlier. Results were given based on the Kaplan-Meier reading with a cutoff at Day 365.	Up to Week 52
Core Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs)	A TEAE was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A TEAE was considered a serious adverse event (SAE) if it resulted in any of the following: death; life-threatening experience; persistent or significant disability or incapacity; inpatient hospitalization or prolongation of hospitalization; congenital anomaly or birth defect; medically important event that may require medical or surgical intervention to prevent one of the outcomes listed. An adverse event of special interest (AESI) was an AE of scientific and medical concern specific to HZN-825. Orthostatic hypotension was considered an AESI. Clinically significant changes in vital signs, electrocardiograms, echocardiograms and laboratory tests recorded after treatment administration were documented as TEAEs.	From 1st dose to last dose + 28 days, Median (min, max) duration was 12.0 (1.0, 13.1) months for Core Phase and 7.0 (1.6, 13.2) months for OLE Phase.
Core Phase: Pre- and Post-dose Concentrations of HZN-825	Pre- and Post-dose Concentrations of HZN-825 were presented.	Day 1 (2-4 hours after the first dose), Week 4 (pre-dose), Week 10, Weeks 16 and 28 (pre-dose and 2-4 hours post-dose), and Weeks 40 and 52 (pre-dose for participants entering OLE).

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2022
• Primary Completion (Actual): July 22, 2024
• Study Completion (Actual): January 2, 2025

Study Registration Dates

• First Submitted: August 27, 2021
• First Submitted That Met QC Criteria: August 27, 2021
• First Posted (Actual): September 2, 2021

Study Record Updates

• Last Update Posted (Estimated): December 3, 2025
• Last Update Submitted That Met QC Criteria: December 1, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Idiopathic Pulmonary Fibrosis; Pulmonary Fibrosis
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Interstitial; Fibrosis; Pathological Conditions, Signs and Symptoms; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis
• Other Study ID Numbers: HZNP-HZN-825-303; 2023-509784-24-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No