Idiopathic Pulmonary FibrosisPhase 2NCT05032066
A Multicenter Trial to Evaluate the Efficacy, Safety and Tolerability of HZN-825 in Subjects With Idiopathic Pulmonary Fibrosis
A Phase 2 study testing HZN-825 in people with Idiopathic Pulmonary Fibrosis, run by Amgen at 82 sites in 19 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Idiopathic Pulmonary Fibrosis
- What is being tested?
- HZN-825
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 153 participants
- Where
- 82 sitesin 19 countries
- Study dates
- 20 Jan 2022to 2 Jan 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female ≥18 years of age at Screening.
- 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.
- 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.
Show all 17Show fewer
- 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.
- 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).
- Meets all of the following criteria during the Screening Period:
- FVC ≥45% predicted of normal
- forced expiratory volume in 1 second (FEV1)/FVC ≥0.7
- Diffusing capacity of the lungs for carbon monoxide (DLCO) corrected for hemoglobin is ≥25% and ≤90% predicted of normal
- Estimated minimum life expectancy of ≥30 months for non-IPF-related disease, in the opinion of the Investigator.
- Vaccinations are up to date given age, comorbidities and local availability prior to trial drug dosing.
- Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the trial.
- 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.
- Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the Extension Phase of the trial.
Who cannot join
- Any of the following cardiovascular diseases:
- uncontrolled, severe hypertension (≥160/100 mmHg), within 6 months of Screening
- myocardial infarction within 6 months of Screening
- unstable cardiac angina within 6 months of Screening
- 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).
- 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.
Show all 30Show fewer
- Clinically significant pulmonary hypertension requiring chronic medical therapy.
- 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.
- Use of rifampin within 2 weeks prior to Day 1 or planned during the trial.
- Malignant condition in the past 5 years (except successfully treated basal/squamous cell carcinoma of the skin or cervical cancer in situ).
- 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.
- 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.
- 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.
- Previous enrollment in this trial or participation in a prior HZN-825 or SAR100842 clinical trial.
- Known history of positive test for human immunodeficiency virus (HIV).
- 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).
- Current alcoholic liver disease, primary biliary cirrhosis or primary sclerosing cholangitis.
- Previous organ transplant (including allogeneic and autologous marrow transplant).
- International normalized ratio >2, prolonged prothrombin time >1.5 × the upper limit of normal (ULN) or partial thromboplastin time >1.5 × ULN at Screening.
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.0 × ULN.
- Estimated glomerular filtration rate <30 mL/min/1.73 m^2 at Screening.
- 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.
- Moderate (Child-Pugh B) to severe (Child-Pugh C) hepatic impairment according to the Child-Pugh scoring system.
- Any confirmed Grade 3 or higher laboratory abnormality.
- Any laboratory abnormality at Screening that, in the opinion of the Investigator, would preclude the participant's entry in the trial.
- 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.
- Any other condition that, in the opinion of the Investigator, would preclude enrollment in the trial.
- Anticipated use of another investigational agent for any condition during the course of the trial.
- 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).
- Estimated minimum life expectancy ≤18 months, in the opinion of the Investigator.
Trial locations and contacts
82 sites in 19 countries.
82 sites in 19 countries
United States22 sites
University of Alabama at Birmingham
Birmingham, Alabama, 35233
St. Francis Medical Institute
Clearwater, Florida, 33765
The Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Stony Brook Medicine Advanced Specialty Care
Commack, New York, 11725
El Paso Pulmonary Association - Elligo
El Paso, Texas, 79902-1124
Clinical Trials Center of Middle Tennessee
Franklin, Tennessee, 37067
Clinical Research of Gastonia
Gastonia, North Carolina, 28054
University of Kansas Medical Center
Kansas City, Kansas, 66160
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, 03756-1000
Nebraska Pulmonary Specialties LLC
Lincoln, Nebraska, 68510
Metroplex Pulmonary and Sleep Medicine Center
McKinney, Texas, 75069
Northwestern Memorial Hospital
Milwaukee, Wisconsin, 53226-3522
Vanderbilt University Medical Center
Nashville, Tennessee, 37204
Central Florida Pulmonary Group PA
Orlando, Florida, 32803
Palmtree Clinical Research
Palm Springs, California, 92262
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Temple University Hospital
Philadelphia, Pennsylvania, 19140-5103
Clinical Research of Rock Hill
Rock Hill, South Carolina, 29732
Shelby Clinical Research
Shelby, North Carolina, 28150
DBC Research Corp.
Tamarac, Florida, 33321
GCP Clinical Research
Tampa, Florida, 33609
Southeastern Research Center
Winston-Salem, North Carolina, 27103
Chile8 sites
Centro de Investigación Curico
Curicó, Maule Region, 3440000
Universidad de Los Andes
Las Condes, Región-MetropolitanadeSantiago, 7550000
MIRES/MYF estudios cli-nicos
Ñuñoa, Región-MetropolitanadeSantiago, 7750495
Enroll SpA
Providencia, Región-MetropolitanadeSantiago, 7500587
Centro Respiratorio Integral LTDA. (CENRESIN)
Quillota, Valparaiso, 2260000
Meditek Ltda
Santiago, Región-MetropolitanadeSantiago, 8330008
Centro de Investigacion del Maule
Talca, 3465586
Clinical Research Chile SpA
Valdivia, 8330033
Argentina6 sites
STAT Research S.A.
Ciudad Autónoma de Buenos Aires, Buenos Aires, C1013AAB
Centro Medico Dra de Salvo
Ciudad de Buenos Aires, C1426ABP
Instituto Ave Pulmo
Mar del Plata, Buenos Aires, 7600
Instituto De Enfermedades Respiratorias E Investigacion Medica
San Juan Bautista, Buenos Aires, 1888
Instituto De Patologías Respiratorias
San Miguel de Tucumán, Tucumán Province, 4000
Instituto Del Buen Aire
Santa Fe, 3000
Greece6 sites
Evangelismos General Hospital of Athens
Athens, Attica, 10676
University General Hospital of Heraklion
Heraklion, 711 10
University General Hospital of Ioannina
Ioannina, 455 00
University General Hospital of Larissa
Larissa, 411 10
Athens Medical Center
Marousi, Attica, 151 25
University General Hospital of Patras
Pátrai, Achaïa, 265 04
Japan6 sites
National Hospital Organization Himeji Medical Center
Himeji-Shi, Hyôgo, 670-8520
Hiroshima Prefectural Hospital
Hiroshima, 734-0004
National Hospital Organization Ibarakihigashi National Hospital
Naka-Gun, Ibaraki, 319-1113
National Hospital Organization Kinki-Chuo Chest Medical Center
Sakaishi, Ôsaka, 591-8025
Medical Hospital of Tokyo Medical and Dental University
Tokyo, 113-8519
Kanagawa Cardiovascular and Respiratory Center
Yokohama, Kanagawa, 235-0041
Mexico4 sites
Oaxaca Site management Organization (OSMO)
Centro, Oaxaca, 68000
CICUM San Miguel
Guadalajara, Jalisco, 44160
Hospital Universitario Dr. Jose Eleuterio González
Monterrey, Nuevo León, 64460
Unidad de Investigación Clínica En Medicina SC
Monterrey, Nuevo León, 64718
South Korea4 sites
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggido, 13620
Korea University Anam Hospital
Seoul, 02841
Asan Medical Center-PPDS
Seoul, 05505
Samsung Medical Center
Seoul
Taiwan4 sites
Kaohsiung Medical University - Chung-Ho Memorial Hospital
Kaohsiung City, 807
China Medical University Hospital - PPDS
Taichung, 404
Far Eastern Memorial Hospital
Taipei, 220
Taipei Veterans General Hospital
Taipei
France3 sites
Hopital Nord AP-HM
Marseille, Bouches-du-Rhône, 13915
Hopital Haut Leveque
Pessac, Gironde, 33604
Hôpital Bretonneau
Tours, Indre-et-Loire, 37044
Poland3 sites
Uniwersyteckie Centrum Kliniczne
Gdansk, Pomeranian Voivodeship
PULMAG Grzegorz Gasior Marzena Kociolek Spolka Cywilna
Katowice, Silesian Voivodeship, 40-752
MCM Krakow - PRATIA - PPDS
Krakow, 30-510
South Africa3 sites
University of Cape Town Lung Institute (UCTLI)
Cape Town, Western Cape, 7700
Dr. Ismail Abdullah Private Practice
Cape Town, Western Cape, 7764
KwaPhila Health Solutions
Durban, KwaZulu-Natal, 4091
Spain3 sites
Hospital Universitario de Bellvitge
L'Hospitalet de Llobregat, Barcelona, 08907
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Universitario Quironsalud Madrid
Pozuelo de Alarcón, Madrid, 28223
Australia2 sites
Royal Adelaide Hospital
Adelaide, South Australia, 5000
Box Hill Hospital
Box Hill, Victoria, 3128
Canada2 sites
Dynamic Drug Advancement Ltd.
Ajax, Ontario, L1S 2J5
St. Joseph's Healthcare Hamilton
Hamilton, Ontario, L8N 4A6
Italy2 sites
Presidio Ospedaliero GB Morgagni L Pierantoni
Forlì, Emilia-Romagna, 47121
Azienda Ospedaliera Universitaria Senese
Siena, 53100
United Kingdom1 site
Connolly Hospital Blanchardstown
Liverpool, L9 7AL
About this study
Official 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
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.
Read more
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:
- Concomitant use of approved IPF therapy (i.e., nintedanib or pirfenidone): yes or no
- 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.
Read the 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
- Being tested
- HZN-825, Placebo
- Keywords
- Pulmonary Fibrosis, Idiopathic Pulmonary Fibrosis
- Medical subject headings
- Idiopathic Pulmonary Fibrosis, Pulmonary Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HZN-825Drug
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| HZN-825 300 mg once daily (QD) | Experimental | 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. Receives: Drug: HZN-825 |
| HZN-825-300 mg twice daily (BID) | Experimental | 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. Receives: Drug: HZN-825 |
| Placebo BID | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: OLE baseline (Week 52) and Week 104
Secondary outcomes (9)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Sep 2021
- Study start20 Jan 2022
- Primary completion22 Jul 2024
- Study completion2 Jan 2025
Why it stopped: The trial was terminated due to not meeting primary or key secondary endpoints.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Idiopathic Pulmonary FibrosisStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 153 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05032066
- Sponsor's protocol ID
- HZNP-HZN-825-303
- Other IDs
- 2023-509784-24-00, 2023
- Status last verified
- Nov 2025
- First submitted
- 27 Aug 2021
- Last updated
- 3 Dec 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT05032066
- Acronym / sponsor ID
- HZNP-HZN-825-303
- Conditions
- Idiopathic Pulmonary Fibrosis
- Keywords
- Pulmonary Fibrosis, Idiopathic Pulmonary Fibrosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The trial was terminated due to not meeting primary or key secondary endpoints.
- Enrolment
- 153 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 20 Jan 2022 (actual)
- Primary completion
- 22 Jul 2024 (actual)
- Study completion
- 2 Jan 2025 (actual)
- First posted
- 2 Sep 2021 (actual)
- Results
- Posted 3 Dec 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Concomitant use of approved IPF therapy (i.e., nintedanib or pirfenidone): yes or no
- 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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| HZN-825 300 mg once daily (QD) | Experimental | Drug: HZN-825Two 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. |
| HZN-825-300 mg twice daily (BID) | Experimental | Drug: HZN-825Two 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 BID | Placebo comparator | Drug: PlaceboMatching 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Male or female ≥18 years of age at Screening.
- 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.
- No recent changes or planned changes to the dose or regimen for IPF therapy, defined as:
- 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.
- 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).
Key exclusion criteria (30 listed)
- Any of the following cardiovascular diseases:
- 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).
- 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.
- Clinically significant pulmonary hypertension requiring chronic medical therapy.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HZN-825Core 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. | Drug | HZN-825 300 mg once daily (QD), HZN-825-300 mg twice daily (BID) |
| PlaceboCore 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. | Drug | Placebo BID |
Primary outcome
Core Phase: Change in FVC % Predicted From Baseline to Week 52
Time frame: Baseline and 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.
Extension Phase: Change in FVC % Predicted From OLE Baseline to Week 104
Time frame: OLE baseline (Week 52) and 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.
9 secondary outcomes
Core Phase: Number of Participants With a Decline in FVC % Predicted ≥10% From Baseline at Week 52
Time frame: Baseline and Week 52
Core Phase: Change in the 6-Minute Walk Test (6MWT) Results From Baseline to Week 52
Time frame: Baseline and Week 52
Core Phase: Change in King's Brief Interstitial Lung Disease (K-BILD) Questionnaire Scores From Baseline to Week 52
Time frame: Baseline and Week 52
Core Phase: Change in Living With IPF (L-IPF) Scores From Baseline to Week 52
Time frame: Baseline and Week 52
Core Phase: Change in Leicester Cough Questionnaire (LCQ) Scores From Baseline to Week 52
Time frame: Baseline to Week 52
Core Phase: Time to First Hospitalization Due to Respiratory Distress From Baseline up to Week 52
Time frame: 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
Time frame: Up to Week 52
Core Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: 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
Time frame: 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).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
Related trials for Idiopathic Pulmonary Fibrosis
Not yet recruitingPhase 3
Long-term Extension Study to Evaluate Safety and Tolerability of Admilparant in Participants With Pulmonary Fibrosis
Pulmonary Fibrosis
Active, not recruitingPhase 2
A Trial to Evaluate Efficacy and Safety of Buloxibutid in People With Idiopathic Pulmonary Fibrosis.
Idiopathic Pulmonary Fibrosis (IPF)
RecruitingPhase 2
Study to Evaluate the Efficacy, Safety, and Tolerability of PIPE 791 in Subjects With Idiopathic Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
RecruitingPhase 2
A Phase IIb Study to Evaluate AZD8965 in Participants With IPF.
Idiopathic Pulmonary Fibrosis (IPF)
Active, not recruitingPhase 3
A Follow-up Study to Test Long-term Treatment With Nerandomilast in People With Pulmonary Fibrosis Who Took Part in a Previous Study With Nerandomilast
Idiopathic Pulmonary Fibrosis, Progressive Pulmonary Fibrosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
82 sites in 19 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing HZN-825 in people with Idiopathic Pulmonary Fibrosis, run by Amgen at 82 sites in 19 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 3 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 82 sites in United States, Chile, Argentina, Greece, Japan and 14 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Core Phase: Change in FVC % Predicted From Baseline to Week 52 (time frame: Baseline and Week 52). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Dec 2025; AzTrials last refreshed its copy on 31 Oct 2026.