A Multicenter Trial to Evaluate the Efficacy, Safety and Tolerability of HZN-825 in Subjects With Idiopathic Pulmonary Fibrosis
- Registration Number
- NCT05032066
- Lead Sponsor
- Amgen
- 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
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 153
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description HZN-825 300 mg once daily (QD) HZN-825 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. HZN-825-300 mg twice daily (BID) HZN-825 Two 150 mg oral tablets given in the morning with a meal and two 150 mg oral tablets given in the evening with a meal; total daily dose 600 mg HZN-825. Placebo BID Placebo 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.
- Primary Outcome Measures
Name Time Method Extension Phase: Change from the HZN-825 baseline, defined as the latest measurement prior to the first dose of HZN-825 in either the core phase or the extension phase in FVC % predicted from Baseline to Week 104 Baseline to Week 104 Core Phase: Change in Forced Vital Capacity (FVC) percent (FVC %) predicted from Baseline to Week 52 Baseline to Week 52 Extension Phase: Change from the Open Label Extension (OLE) baseline, defined as the latest measurement prior to the first dose of HZN-825 in the extension phase in FVC % predicted from Baseline to Week 104 Baseline to Week 104
- Secondary Outcome Measures
Name Time Method Core Phase: Incidence and frequency of use of concomitant medication(s) Day 1 to Week 52 Core Phase: Change from baseline in the 6MWT (Six-Minute Walk Test) results to Week 52 Baseline to Week 52 The 6-minute walk test measures the distance that a participant can quickly walk on a flat, hard surface in 6 minutes. 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. The 6MWT will be performed according to ATS guidelines for the 6MWT.
Core Phase: Incidence of adverse events of special interest (AESIs): orthostatic hypotension Day 1 to Week 52 Core Phase: Change in abnormal clinical safety laboratory test results as reported as TEAEs Day 1 to Week 52 Extension Phase: Incidence and frequency of use of concomitant medication(s) Baseline to Week 104 Core Phase: Change from baseline in K-BILD (King's Brief Interstitial Lung Disease) scores to Week 52 Baseline to Week 52 The King's Brief Interstitial Lung Disease Questionnaire 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. The 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. The minimal clinically important difference for the K-BILD total score as determined by both anchor and distribution methods is a change of 5 units.
Core Phase: Change from baseline in L-IPF (Living with IPF[Idiopathic Pulmonary Fibrosis]) scores to Week 52 Baseline to Week 52 The questionnaire evaluates how living with IPF has impacted the quality of life of the participant with IPF. There are two 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. All items in both modules have response options in a 5-point (0-4) numerical rating scale, where 0 = not at all and 4 = all the time.
Core Phase: Incidence of treatment emergent adverse events (TEAEs) Day 1 to Week 52 Extension Phase: Incidence of TEAEs Day 1 to Week 104 Extension Phase: Change from trial baseline in abnormal and clinically significant 12-lead ECG) measurements as reported as TEAEs. Baseline to Week 104 Core Phase: Incidence of serous adverse events (SAEs) Day 1 to Week 52 Core Phase: Change from baseline in LCQ (Leicester Cough Questionnaire) scores to Week 52 Baseline to Week 52 The LCQ is a participant-reported questionnaire evaluating the impact of cough on quality of life. The LCQ comprises 19 items and takes 5-10 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: 1-7). A total score (range: 3 to 21) is also calculated. Higher scores indicate better quality of life.
Core Phase: Time to first hospitalization due to respiratory distress up to Week 52 Baseline to Week 52 Core Phase: Time to first onset of the composite endpoint of PFS (progression-free survival) from Baseline up to Week 52, where progression includes decline in FVC % predicted ≥10% or death Baseline to Week 52 Core Phase: Change in abnormal and clinically significant vital signs as reported as TEAEs Day 1 to Week 52 Core Phase: Change in abnormal and clinically significant 12-lead electrocardiogram (ECG) or echocardiogram measurements as reported as TEAEs. Day 1 to Week 52 Extension Phase: Incidence of AESIs: orthostatic hypotension Day 1 to Week 104 Extension Phase: Change from trial baseline in abnormal and clinically significant vital signs reported as TEAEs Baseline to Week 104 Extension Phase: Change from trial baseline in abnormal clinical safety laboratory test results as reported as TEAEs Baseline to Week 104
Trial Locations
- Locations (82)
Dr. Ismail Abdullah Private Practice
🇿🇦Cape Town, Western Cape, South Africa
Instituto De Enfermedades Respiratorias E Investigacion Medica
🇦🇷Florencio Varela, Buenos Aires, Argentina
The Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Centro Respiratorio Integral LTDA. (CENRESIN)
🇨🇱Quillota, Valparaíso, Chile
Temple University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Connolly Hospital Blanchardstown
🇬🇧Liverpool, United Kingdom
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
China Medical University Hospital - PPDS
🇨🇳Taichung, Taiwan
Stony Brook Medicine Advanced Specialty Care
🇺🇸Commack, New York, United States
El Paso Pulmonary Association - Elligo
🇺🇸El Paso, Texas, United States
Centro de Investigación Curico
🇨🇱Curico, Maule, Chile
Hopital Nord AP-HM
🇫🇷Marseille, Bouches-du-Rhône, France
Hospital Universitario Quironsalud Madrid
🇪🇸Pozuelo De Alarcón, Madrid, Spain
Centro de Investigacion del Maule
🇨🇱Talca, Chile
Lungenklinik Hemer
🇩🇪Hemer, Nordrhein-Westfalen, Germany
Kanagawa Cardiovascular and Respiratory Center
🇯🇵Yokohama-Shi, Kanagawa, Japan
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Instituto De Patologías Respiratorias
🇦🇷San Miguel De Tucumán, Tucumán, Argentina
Asan Medical Center-PPDS
🇰🇷Seoul, Korea, Republic of
St. Francis Medical Institute
🇺🇸Clearwater, Florida, United States
Nebraska Pulmonary Specialties LLC
🇺🇸Lincoln, Nebraska, United States
STAT Research S.A.
🇦🇷Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina
Instituto Ave Pulmo
🇦🇷Mar Del Plata, Buenos Aires, Argentina
Centro Medico Dra de Salvo
🇦🇷Ciudad de Buenos Aires, Argentina
Instituto Del Buen Aire
🇦🇷Santa Fe, Argentina
Central Florida Pulmonary Group PA
🇺🇸Orlando, Florida, United States
Enroll SpA
🇨🇱Providencia, Región-MetropolitanadeSantiago, Chile
Clinical Research Chile SpA
🇨🇱Valdivia, Chile
University General Hospital of Patras
🇬🇷Patras, Achaïa, Greece
Evangelismos General Hospital of Athens
🇬🇷Athens, Attiki, Greece
University General Hospital of Ioannina
🇬🇷Ioannina, Greece
University General Hospital of Heraklion
🇬🇷Iraklio, Greece
Azienda Ospedaliera Universitaria Senese
🇮🇹Siena, Italy
Medical Hospital of Tokyo Medical and Dental University
🇯🇵Tokyo, Japan
Hospital Universitario Dr. Jose Eleuterio González
🇲🇽Monterrey, Nuevo León, Mexico
Oaxaca Site management Organization (OSMO)
🇲🇽Centro, Oaxaca, Mexico
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Pomorskie, Poland
Presidio Ospedaliero GB Morgagni L Pierantoni
🇮🇹Forlì, Emilia-Romagna, Italy
CICUM San Miguel
🇲🇽Guadalajara, Jalisco, Mexico
Universidad de Los Andes
🇨🇱Las Condes, Región-MetropolitanadeSantiago, Chile
MIRES/MYF estudios cli-nicos
🇨🇱Ñuñoa, Región-MetropolitanadeSantiago, Chile
Hiroshima Prefectural Hospital
🇯🇵Hiroshima, Japan
Unidad de Investigación Clínica En Medicina SC
🇲🇽Monterrey, Nuevo León, Mexico
Kaohsiung Medical University - Chung-Ho Memorial Hospital
🇨🇳Kaohsiung City, Taiwan
University of Cape Town Lung Institute (UCTLI)
🇿🇦Cape Town, Western Cape, South Africa
Hôpital Bretonneau
🇫🇷Tours, Indre-et-Loire, France
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
DBC Research Corp.
🇺🇸Tamarac, Florida, United States
Clinical Trials Center of Middle Tennessee
🇺🇸Franklin, Tennessee, United States
Box Hill Hospital
🇦🇺Box Hill, Victoria, Australia
Meditek Ltda
🇨🇱Santiago, Región-MetropolitanadeSantiago, Chile
Hopital Haut Leveque
🇫🇷Pessac, Gironde, France
Athens Medical Center
🇬🇷Marousi, Attiki, Greece
National Hospital Organization Himeji Medical Center
🇯🇵Himeji-Shi, Hyôgo, Japan
Clinical Research of Rock Hill
🇺🇸Rock Hill, South Carolina, United States
University General Hospital of Larissa
🇬🇷Larisa, Greece
National Hospital Organization Ibarakihigashi National Hospital
🇯🇵Naka-Gun, Ibaraki, Japan
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Dynamic Drug Advancement Ltd.
🇨🇦Ajax, Ontario, Canada
National Hospital Organization Kinki-Chuo Chest Medical Center
🇯🇵Sakai-Shi, Ôsaka, Japan
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Gyeonggido, Korea, Republic of
Erasmus MC
🇳🇱Rotterdam, Netherlands
Far Eastern Memorial Hospital
🇨🇳Taipei, Taiwan
Kocaeli University Hospital
🇹🇷Kocaeli, Turkey
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
PULMAG Grzegorz Gasior Marzena Kociolek Spolka Cywilna
🇵🇱Katowice, Slaskie, Poland
MCM Krakow - PRATIA - PPDS
🇵🇱Kraków, Poland
KwaPhila Health Solutions
🇿🇦Durban, Kwazulu - Natal, South Africa
Hospital Universitario de Bellvitge
🇪🇸L'Hospitalet De Llobregat, Barcelona, Spain
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
GCP Clinical Research
🇺🇸Tampa, Florida, United States
Northwestern Memorial Hospital
🇺🇸Milwaukee, Wisconsin, United States
Palmtree Clinical Research
🇺🇸Palm Springs, California, United States
Shelby Clinical Research
🇺🇸Shelby, North Carolina, United States
Southeastern Research Center
🇺🇸Winston-Salem, North Carolina, United States
Metroplex Pulmonary and Sleep Medicine Center
🇺🇸McKinney, Texas, United States
Clinical Research of Gastonia
🇺🇸Gastonia, North Carolina, United States
St. Joseph's Healthcare Hamilton
🇨🇦Hamilton, Ontario, Canada
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States