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

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ClinicalTrials.gov Identifier: NCT05032066
Recruitment Status : Recruiting
First Posted : September 2, 2021
Last Update Posted : September 2, 2021
Sponsor:
Information provided by (Responsible Party):
Horizon Pharma Ireland, Ltd., Dublin Ireland ( Horizon Therapeutics Ireland DAC )

Brief Summary:

This is a randomized, double-blind, placebo-controlled, repeat-dose, multicenter trial to evaluate the efficacy, safety and tolerability of HZN-825 in subjects with IPF. Subjects will be screened within 8 weeks prior to the Baseline (Day 1) Visit. Approximately 360 subjects 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 placebo for 52 weeks using the following 2 stratification factors:

  1. Prior use of approved IPF therapy (i.e., nintedanib or pirfenidone): yes or no
  2. FVC % predicted at Baseline: ≥70% or <70%

Condition or disease Intervention/treatment Phase
Idiopathic Pulmonary Fibrosis Drug: HZN-825 Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 360 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : August 25, 2021
Estimated Primary Completion Date : September 2023
Estimated Study Completion Date : October 2023


Arm Intervention/treatment
Experimental: 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
Drug: 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

Experimental: 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
Drug: 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 Comparator: 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 daily dose 4 placebo tablets
Drug: 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 daily dose 4 placebo tablets
Other Name: Placebo BID




Primary Outcome Measures :
  1. Change in Forced Vital Capacity (FVC) percent predicted from Baseline to Week 52 [ Time Frame: Baseline to Week 52 ]

Secondary Outcome Measures :
  1. Proportion of Participants with decline in FVC % predicted ≥10% from Baseline at Week 52 [ Time Frame: Week 52 ]
  2. Change from Baseline in the 6MWT (Six-Minute Walk Test) results to Week 52 [ Time Frame: 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.

  3. Change from Baseline in K-BILD (King's Brief Interstitial Lung Disease) scores to Week 52 [ Time Frame: 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.

  4. Change from Baseline in L-IPF (Living with IPF[Idiopathic Pulmonary Fibrosis]) scores to Week 52 [ Time Frame: 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.

  5. Change from Baseline in LCQ (Leicester Cough Questionnaire) scores to Week 52 [ Time Frame: 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.

  6. Time to first hospitalization due to respiratory distress up to Week 52 [ Time Frame: Baseline to Week 52 ]
  7. 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 [ Time Frame: Baseline to Week 52 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent.
  2. Male or female between the ages of 18 and 80 years, inclusive, at Screening.
  3. Diagnosis of IPF, as defined by American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Society (ALAT) guidelines [Raghu et al., 2018]; the date of diagnosis of IPF should be ≥1 year to ≤7 years prior to Screening.
  4. Not currently being treated with specific IPF therapy for the reasons below:

    1. intolerant or not responsive to approved IPF therapies
    2. ineligible to receive approved IPF therapies
    3. declines approved IPF therapies
  5. Lung 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 subject'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.
  6. HRCT shows ≥10% to <50% parenchymal fibrosis (reticulation) and <25% honeycombing and the extent of fibrotic changes is greater than the extent of emphysema on the most recent HRCT scan (central reviewer determined).
  7. Meets all of the following criteria during the Screening Period:

    1. FVC ≥45% and ≤80% predicted of normal
    2. forced expiratory volume in 1 second (FEV1)/FVC ≥0.7
    3. DLCO corrected for hemoglobin is ≥30% and ≤90% predicted of normal
  8. Estimated minimum life expectancy of ≥30 months for non-IPF-related disease, in the opinion of the Investigator.
  9. Vaccinations are up to date given age, comorbidities (e.g., severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]), pneumococcal pneumonia, herpes zoster, tetanus) and local availability prior to trial drug dosing.
  10. Willing and able to comply with the prescribed treatment protocol and evaluations for the duration 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 subject 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 A. Prednisone ≤10 mg/day (or equivalent dosing of glucocorticoids) is allowed. Treatment with any other 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 1 month after last dose of trial drug. Male subjects must refrain from sperm donation and females from egg/ova donation for this same time period.
  9. Pregnant or lactating women and women who plan to become pregnant or breast feed during the trial and within 1 month 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.
  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 or aspartate aminotransferase >2.0 × ULN.
  18. Estimated glomerular filtration rate <30 mL/min/1.73 m2 at Screening.
  19. Total bilirubin >2 × 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 verified Grade 4 laboratory abnormality.
  22. Any acute laboratory abnormality at Screening that, in the opinion of the Investigator, would preclude the subject's participation 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05032066


Contacts
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Contact: Horizon Therapeutics 866-479-6742 clinicaltrials@horizontherapeutics.com

Locations
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United States, Florida
St. Francis Medical Institute Recruiting
Clearwater, Florida, United States, 33765
Contact: Amber Dunn    727-447-3000    adunn@stfrancismed.com   
Principal Investigator: Francis Averill, MD         
Advanced Pulmonary Research Institute Recruiting
Loxahatchee Groves, Florida, United States, 33470
Contact: Liudmila Moreiras    561-795-1023    aprinpmila@gmail.com   
Principal Investigator: Neal Warshoff, DO         
United States, Texas
Metroplex Pulmonary and Sleep Medicine Center Recruiting
McKinney, Texas, United States, 75069
Contact: Ambreen Ahmed    972-838-1892    aahmed@mpsleepcenter.com   
Principal Investigator: Shahrukh Kureishy, MD         
Sponsors and Collaborators
Horizon Therapeutics Ireland DAC
Investigators
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Study Director: Anthony Barbieri, MD Horizon Therapeutics
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Responsible Party: Horizon Therapeutics Ireland DAC
ClinicalTrials.gov Identifier: NCT05032066    
Other Study ID Numbers: HZNP-HZN-825-303
2021-001253-32 ( EudraCT Number )
First Posted: September 2, 2021    Key Record Dates
Last Update Posted: September 2, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Horizon Pharma Ireland, Ltd., Dublin Ireland ( Horizon Therapeutics Ireland DAC ):
Pulmonary Fibrosis
Additional relevant MeSH terms:
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Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Fibrosis
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases