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

NCT ID: NCT05032066

Last Updated: 2025-12-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 153 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-20
• Study Completion Date: 2025-01-02

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.

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

Conditions

Idiopathic Pulmonary Fibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

HZN-825

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

HZN-825

Intervention Type: DRUG

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 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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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.

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.

Exclusion Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Palmtree Clinical Research

Palm Springs, California, United States

St. Francis Medical Institute

Clearwater, Florida, United States

Central Florida Pulmonary Group PA

Orlando, Florida, United States

DBC Research Corp.

Tamarac, Florida, United States

GCP Clinical Research

Tampa, Florida, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Nebraska Pulmonary Specialties LLC

Lincoln, Nebraska, United States

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Stony Brook Medicine Advanced Specialty Care

Commack, New York, United States

Clinical Research of Gastonia

Gastonia, North Carolina, United States

Shelby Clinical Research

Shelby, North Carolina, United States

Southeastern Research Center

Winston-Salem, North Carolina, United States

The Cleveland Clinic Foundation

Cleveland, Ohio, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Temple University Hospital

Philadelphia, Pennsylvania, United States

Clinical Research of Rock Hill

Rock Hill, South Carolina, United States

Clinical Trials Center of Middle Tennessee

Franklin, Tennessee, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

El Paso Pulmonary Association - Elligo

El Paso, Texas, United States

Metroplex Pulmonary and Sleep Medicine Center

McKinney, Texas, United States

Northwestern Memorial Hospital

Milwaukee, Wisconsin, United States

STAT Research S.A.

Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

Instituto Ave Pulmo

Mar del Plata, Buenos Aires, Argentina

Instituto De Enfermedades Respiratorias E Investigacion Medica

San Juan Bautista, Buenos Aires, Argentina

Instituto De Patologías Respiratorias

San Miguel de Tucumán, Tucumán Province, Argentina

Centro Medico Dra de Salvo

Ciudad de Buenos Aires, , Argentina

Instituto Del Buen Aire

Santa Fe, , Argentina

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Box Hill Hospital

Box Hill, Victoria, Australia

Dynamic Drug Advancement Ltd.

Ajax, Ontario, Canada

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, Canada

Centro de Investigación Curico

Curicó, Maule Region, Chile

Centro Respiratorio Integral LTDA. (CENRESIN)

Quillota, Región de Valparaíso, Chile

Universidad de Los Andes

Las Condes, Región-MetropolitanadeSantiago, Chile

MIRES/MYF estudios cli-nicos

Ñuñoa, Región-MetropolitanadeSantiago, Chile

Enroll SpA

Providencia, Región-MetropolitanadeSantiago, Chile

Meditek Ltda

Santiago, Región-MetropolitanadeSantiago, Chile

Centro de Investigacion del Maule

Talca, , Chile

Clinical Research Chile SpA

Valdivia, , Chile

Hopital Nord AP-HM

Marseille, Bouches-du-Rhône, France

Hopital Haut Leveque

Pessac, Gironde, France

Hôpital Bretonneau

Tours, Indre-et-Loire, France

Lungenklinik Hemer

Hemer, North Rhine-Westphalia, Germany

University General Hospital of Patras

Pátrai, Achaïa, Greece

Evangelismos General Hospital of Athens

Athens, Attica, Greece

Athens Medical Center

Marousi, Attica, Greece

University General Hospital of Heraklion

Heraklion, , Greece

University General Hospital of Ioannina

Ioannina, , Greece

University General Hospital of Larissa

Larissa, , Greece

Presidio Ospedaliero GB Morgagni L Pierantoni

Forlì, Emilia-Romagna, Italy

Azienda Ospedaliera Universitaria Senese

Siena, , Italy

National Hospital Organization Himeji Medical Center

Himeji-Shi, Hyôgo, Japan

National Hospital Organization Ibarakihigashi National Hospital

Naka-Gun, Ibaraki, Japan

Kanagawa Cardiovascular and Respiratory Center

Yokohama, Kanagawa, Japan

Hiroshima Prefectural Hospital

Hiroshima, , Japan

Medical Hospital of Tokyo Medical and Dental University

Tokyo, , Japan

National Hospital Organization Kinki-Chuo Chest Medical Center

Sakaishi, Ôsaka, Japan

CICUM San Miguel

Guadalajara, Jalisco, Mexico

Hospital Universitario Dr. Jose Eleuterio González

Monterrey, Nuevo León, Mexico

Unidad de Investigación Clínica En Medicina SC

Monterrey, Nuevo León, Mexico

Oaxaca Site management Organization (OSMO)

Centro, Oaxaca, Mexico

Erasmus MC

Rotterdam, , Netherlands

Uniwersyteckie Centrum Kliniczne

Gdansk, Pomeranian Voivodeship, Poland

PULMAG Grzegorz Gasior Marzena Kociolek Spolka Cywilna

Katowice, Silesian Voivodeship, Poland

MCM Krakow - PRATIA - PPDS

Krakow, , Poland

KwaPhila Health Solutions

Durban, KwaZulu-Natal, South Africa

University of Cape Town Lung Institute (UCTLI)

Cape Town, Western Cape, South Africa

Dr. Ismail Abdullah Private Practice

Cape Town, Western Cape, South Africa

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggido, South Korea

Korea University Anam Hospital

Seoul, , South Korea

Asan Medical Center-PPDS

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Hospital Universitario de Bellvitge

L'Hospitalet de Llobregat, Barcelona, Spain

Hospital Universitario Quironsalud Madrid

Pozuelo de Alarcón, Madrid, Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Kaohsiung Medical University - Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

China Medical University Hospital - PPDS

Taichung, , Taiwan

Far Eastern Memorial Hospital

Taipei, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

Kocaeli University Hospital

Kocaeli, , Turkey (Türkiye)

Connolly Hospital Blanchardstown

Liverpool, , United Kingdom

Countries

United States; Argentina; Australia; Canada; Chile; France; Germany; Greece; Italy; Japan; Mexico; Netherlands; Poland; South Africa; South Korea; Spain; Taiwan; Turkey (Türkiye); United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

2023-509784-24-00

Identifier Type: CTIS

Identifier Source: secondary_id

HZNP-HZN-825-303

Identifier Type: -

Identifier Source: org_study_id