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

Phase 2

Terminated

• Conditions: Idiopathic Pulmonary Fibrosis
• Interventions: Drug: HZN-825; Drug: Placebo

• 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

Study Timeline

• Study Start: 2021-08-25
• Study First Submitted: 2021-08-27
• Study First Submitted QC: 2021-08-27
• Study First Posted: 2021-09-02
• Primary Completion: 2024-07-22
• Study Completion: 2025-01-02
• Status Verified: 2025-02
• Disposition First Posted: 2025-02-04
• Disposition First Submitted: 2025-03-04
• Last Update Submitted: 2025-03-04
• Last Update Posted: 2025-03-06

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 153

Inclusion Criteria

Not provided

Exclusion Criteria

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 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
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

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: 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
Extension Phase: Incidence of TEAEs	Day 1 to Week 104

Trial Locations

Locations (82)

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

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