NCT05032066

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

Terminated Phase 2 Results posted Last updated 3 December 2025

What this trial tests

Phase 2 trial testing HZN-825 in Idiopathic Pulmonary Fibrosis in 153 participants. Terminated before completion.

Timeline

20 January 2022

Primary endpoint
22 July 2024

2 January 2025

Quick facts

Lead sponsor	Amgen
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	153
Start date	20 January 2022
Primary completion	22 July 2024
Estimated completion	2 January 2025
Sites	82 locations across Italy, Japan, Taiwan, Poland, South Korea, Netherlands, Mexico, United States

Drugs / interventions tested

• HZN-825 — full drug profile →
• Placebo

Conditions studied

• Idiopathic Pulmonary Fibrosis — all drugs for Idiopathic Pulmonary Fibrosis →

Sponsor

Amgen — full company profile →

Who can join

18 and older, any sex, with Idiopathic Pulmonary Fibrosis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Core Phase: Change in FVC % Predicted From Baseline to Week 52 Primary · 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.

Group	Value	95% CI
HZN-825 300 mg QD Then HZN-825 300 mg BID	-4.13	± 1.045
HZN-825 300 mg BID	-3.38	± 1.092
Placebo Then HZN-825 300 mg BID	-2.99	± 1.025

Extension Phase: Change in FVC % Predicted From OLE Baseline to Week 104 Primary · 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, ethnicit

Group	Value	95% CI
HZN-825 300 mg QD Then HZN-825 300 mg BID	11.38	± 23.237
HZN-825 300 mg BID	-0.63	± 16.283
Placebo Then HZN-825 300 mg BID	-2.62	± 6.305

Core Phase: Number of Participants With a Decline in FVC % Predicted ≥10% From Baseline at Week 52 Secondary · 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.

Group	Value	95% CI
HZN-825 300 mg QD Then HZN-825 300 mg BID	6
HZN-825 300 mg BID	7
Placebo Then HZN-825 300 mg BID	4

Core Phase: Change in the 6-Minute Walk Test (6MWT) Results From Baseline to Week 52 Secondary · Baseline and 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.

Group	Value	95% CI
HZN-825 300 mg QD Then HZN-825 300 mg BID	14.00	± 12.990
HZN-825 300 mg BID	-3.95	± 13.081
Placebo Then HZN-825 300 mg BID	-2.71	± 12.757

Core Phase: Change in King's Brief Interstitial Lung Disease (K-BILD) Questionnaire Scores From Baseline to Week 52 Secondary · Baseline and 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.

Group	Value	95% CI
HZN-825 300 mg QD Then HZN-825 300 mg BID	-1.5	± 1.65
HZN-825 300 mg BID	-1.4	± 1.67
Placebo Then HZN-825 300 mg BID	-0.3	± 1.62

Core Phase: Change in Living With IPF (L-IPF) Scores From Baseline to Week 52 Secondary · Baseline and 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.

L-IPF Symptoms Total Score

Group	Value	95% CI
HZN-825 300 mg QD Then HZN-825 300 mg BID	4.0	± 1.42
HZN-825 300 mg BID	2.6	± 1.45
Placebo Then HZN-825 300 mg BID	0.6	± 1.39

L-IPF Impact Total Score

Group	Value	95% CI
HZN-825 300 mg QD Then HZN-825 300 mg BID	3.1	± 1.93
HZN-825 300 mg BID	1.3	± 1.97
Placebo Then HZN-825 300 mg BID	-0.8	± 1.90

Core Phase: Change in Leicester Cough Questionnaire (LCQ) Scores From Baseline to Week 52 Secondary · 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.

Group	Value	95% CI
HZN-825 300 mg QD Then HZN-825 300 mg BID	0.19	± 0.463
HZN-825 300 mg BID	-0.45	± 0.468
Placebo Then HZN-825 300 mg BID	0.54	± 0.453

Core Phase: Time to First Hospitalization Due to Respiratory Distress From Baseline up to Week 52 Secondary · 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.

Group	Value	95% CI
HZN-825 300 mg QD Then HZN-825 300 mg BID	NA	NA – NA
HZN-825 300 mg BID	NA	NA – NA
Placebo Then HZN-825 300 mg BID	NA	NA – NA

Core Phase: Time to First Onset of the Composite Endpoint of Progression-Free Survival (PFS) From Baseline up to Week 52 Secondary · 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.

Group	Value	95% CI
HZN-825 300 mg QD Then HZN-825 300 mg BID	NA	NA – NA
HZN-825 300 mg BID	NA	357 – NA
Placebo Then HZN-825 300 mg BID	NA	NA – NA

Core Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs) Secondary · 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.

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 in

Core Phase: TEAEs

Group	Value	95% CI
HZN-825 300 mg QD Then HZN-825 300 mg BID	38
HZN-825 300 mg BID	42
Placebo Then HZN-825 300 mg BID	38

Core Phase: SAEs

Group	Value	95% CI
HZN-825 300 mg QD Then HZN-825 300 mg BID	10
HZN-825 300 mg BID	14
Placebo Then HZN-825 300 mg BID	9

Core Phase: AESIs

Group	Value	95% CI
HZN-825 300 mg QD Then HZN-825 300 mg BID	1
HZN-825 300 mg BID	2
Placebo Then HZN-825 300 mg BID	1

Extension Phase: TEAEs

Group	Value	95% CI
HZN-825 300 mg QD Then HZN-825 300 mg BID	27
HZN-825 300 mg BID	22
Placebo Then HZN-825 300 mg BID	33

Extension Phase: SAEs

Group	Value	95% CI
HZN-825 300 mg QD Then HZN-825 300 mg BID	8
HZN-825 300 mg BID	6
Placebo Then HZN-825 300 mg BID	9

Extension Phase: AESIs

Group	Value	95% CI
HZN-825 300 mg QD Then HZN-825 300 mg BID	0
HZN-825 300 mg BID	1
Placebo Then HZN-825 300 mg BID	0

Core Phase: Pre- and Post-dose Concentrations of HZN-825 Secondary · 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).

Pre- and Post-dose Concentrations of HZN-825 were presented.

Day 1 (Post-dose)

Group	Value	95% CI
HZN-825 300 mg QD Then HZN-825 300 mg BID	16676.2	± 11030.30
HZN-825 300 mg BID	16209.4	± 11592.69

Week 4 (Pre-dose)

Group	Value	95% CI
HZN-825 300 mg QD Then HZN-825 300 mg BID	6521.3	± 7756.18
HZN-825 300 mg BID	18360.0	± 11953.98

Week 10

Group	Value	95% CI
HZN-825 300 mg QD Then HZN-825 300 mg BID	11372.8	± 11123.02
HZN-825 300 mg BID	23807.8	± 13864.61

Week 16 (Pre-dose)

Group	Value	95% CI
HZN-825 300 mg QD Then HZN-825 300 mg BID	5296.4	± 3093.68
HZN-825 300 mg BID	16889.8	± 9952.20

Week 16 (Post-dose)

Group	Value	95% CI
HZN-825 300 mg QD Then HZN-825 300 mg BID	21162.9	± 11543.77
HZN-825 300 mg BID	24629.3	± 11871.17

Week 28 (Pre-dose)

Group	Value	95% CI
HZN-825 300 mg QD Then HZN-825 300 mg BID	5435.8	± 4125.22
HZN-825 300 mg BID	19258.1	± 10368.10

Week 28 (Post-dose)

Group	Value	95% CI
HZN-825 300 mg QD Then HZN-825 300 mg BID	19410.7	± 13812.87
HZN-825 300 mg BID	27598.4	± 13634.06

Week 40 (Pre-dose)

Group	Value	95% CI
HZN-825 300 mg QD Then HZN-825 300 mg BID	8487.6	± 9209.61
HZN-825 300 mg BID	20702.0	± 13362.76

Adverse events — posted to ClinicalTrials.gov

Time frame: Death: From randomization to end of study (EOS), Median (min, max) was 17.7 (0.1, 25.9) months. TEAE: 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.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Core Phase: HZN-825 300mg QD

Serious: 10/49 (20%)

Deaths: 3/49

Core Phase: HZN-825 300mg BID

Serious: 14/52 (27%)

Deaths: 4/52

Core Phase: Placebo

Serious: 9/52 (17%)

Deaths: 2/52

OLE Phase: HZN-825 300mg BID

Serious: 23/110 (21%)

Deaths: 11/110

Serious adverse events (58 terms)

Reaction	System	Core Phase: HZN-825 300mg QD	Core Phase: HZN-825 300mg …	Core Phase: Placebo	OLE Phase: HZN-825 300mg BID
Idiopathic pulmonary fibrosis	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—
Pneumonia viral	Infections and infestations	—	—	—	—
Septic shock	Infections and infestations	—	—	—	—
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Acute myocardial infarction	Cardiac disorders	—	—	—	—
Angina pectoris	Cardiac disorders	—	—	—	—
Angina unstable	Cardiac disorders	—	—	—	—
Atrial fibrillation	Cardiac disorders	—	—	—	—
Cardiac arrest	Cardiac disorders	—	—	—	—
Myocardial infarction	Cardiac disorders	—	—	—	—
Right ventricular failure	Cardiac disorders	—	—	—	—
Retinal artery thrombosis	Eye disorders	—	—	—	—
Abdominal distension	Gastrointestinal disorders	—	—	—	—
Gastric ulcer	Gastrointestinal disorders	—	—	—	—
Oesophageal varices haemorrhage	Gastrointestinal disorders	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—
Bile duct stone	Hepatobiliary disorders	—	—	—	—
Cholangitis acute	Hepatobiliary disorders	—	—	—	—
Cholecystitis acute	Hepatobiliary disorders	—	—	—	—
Gallbladder rupture	Hepatobiliary disorders	—	—	—	—
Hepatic necrosis	Hepatobiliary disorders	—	—	—	—
Atypical mycobacterial infection	Infections and infestations	—	—	—	—
Bacterial sepsis	Infections and infestations	—	—	—	—

Other adverse events (16 terms — click to expand)

Reaction	System	Core Phase: HZN-825 300mg QD	Core Phase: HZN-825 300mg …	Core Phase: Placebo	OLE Phase: HZN-825 300mg BID
Bronchitis	Infections and infestations	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—
Activated partial thromboplastin time prolonged	Investigations	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Idiopathic pulmonary fibrosis	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Gastrooesophageal reflux disease	Gastrointestinal disorders	—	—	—	—
Pyrexia	General disorders	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—
Headache	Nervous system disorders	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—

Most-reported serious reactions: Idiopathic pulmonary fibrosis, Respiratory failure, Pneumonia, Pneumonia viral, Septic shock, Acute respiratory failure, Acute myocardial infarction, Angina pectoris.

Data from ClinicalTrials.gov NCT05032066 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Mitochondrial network dynamics in pulmonary disease: Bridging the gap between inflammation, oxidative stress, and bioenergetics.
   Pokharel MD, Garcia-Flores A, Marciano D, Franco MC, et al · · 2024 · cited 73× · PMID 38295575 · DOI 10.1016/j.redox.2024.103049
2. Progress in understanding and treating idiopathic pulmonary fibrosis: recent insights and emerging therapies.
   Guo H, Sun J, Zhang S, Nie Y, et al · · 2023 · cited 23× · PMID 37608885 · DOI 10.3389/fphar.2023.1205948
3. Highlights on Future Treatments of IPF: Clues and Pitfalls.
   Libra A, Sciacca E, Muscato G, Sambataro G, et al · · 2024 · cited 13× · PMID 39125962 · DOI 10.3390/ijms25158392
4. COVID-19 and fibrosis: Mechanisms, clinical relevance, and future perspectives.
   Saifi MA, Bansod S, Godugu C. · · 2022 · cited 12× · PMID 36075378 · DOI 10.1016/j.drudis.2022.103345
5. Lysophosphatidic acid receptor 1 inhibition: a potential treatment target for pulmonary fibrosis.
   Volkmann ER, Denton CP, Kolb M, Wijsenbeek-Lourens MS, et al · · 2024 · cited 11× · PMID 39009409 · DOI 10.1183/16000617.0015-2024
6. Decoding lysophosphatidic acid signaling in physiology and disease: mapping the multimodal and multinodal signaling networks.
   Nadhan R, Nath K, Basu S, Isidoro C, et al · · 2025 · cited 6× · PMID 41068071 · DOI 10.1038/s41392-025-02423-4
7. Vascular involvement in idiopathic pulmonary fibrosis.
   Mondoni M, Rinaldo R, Ryerson CJ, Albrici C, et al · · 2024 · cited 6× · PMID 39588083 · DOI 10.1183/23120541.00550-2024
8. The Plastic Interplay between Lung Regeneration Phenomena and Fibrotic Evolution: Current Challenges and Novel Therapeutic Perspectives.
   Lettieri S, Bertuccio FR, Del Frate L, Perrotta F, et al · · 2023 · cited 6× · PMID 38203718 · DOI 10.3390/ijms25010547