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

Sponsor
Horizon Therapeutics Ireland DAC (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05032066
Collaborator
(none)
360
Enrollment
51
Locations
3
Arms
25.2
Anticipated Duration (Months)
7.1
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

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
Phase 2

Study Design

Study Type:
Interventional
Anticipated 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 :
Aug 25, 2021
Anticipated Primary Completion Date :
Sep 1, 2023
Anticipated Study Completion Date :
Oct 1, 2023

Arms and Interventions

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 Names:
  • Placebo BID

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change in Forced Vital Capacity (FVC) percent predicted from Baseline to Week 52 [Baseline to Week 52]

    Secondary Outcome Measures

    1. Proportion of Participants with decline in FVC % predicted ≥10% from Baseline at Week 52 [Week 52]

    2. 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.

    3. 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.

    4. 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.

    5. 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.

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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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:

    5. intolerant or not responsive to approved IPF therapies

    6. ineligible to receive approved IPF therapies

    7. declines approved IPF therapies

    8. 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.

    9. 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).

    10. Meets all of the following criteria during the Screening Period:

    11. FVC ≥45% and ≤80% predicted of normal

    12. forced expiratory volume in 1 second (FEV1)/FVC ≥0.7

    13. DLCO corrected for hemoglobin is ≥30% and ≤90% predicted of normal

    14. Estimated minimum life expectancy of ≥30 months for non-IPF-related disease, in the opinion of the Investigator.

    15. 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.

    16. 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:

    2. uncontrolled, severe hypertension (≥160/100 mmHg), within 6 months of Screening

    3. myocardial infarction within 6 months of Screening

    4. unstable cardiac angina within 6 months of Screening

    5. 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).

    6. 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.

    7. Clinically significant pulmonary hypertension requiring chronic medical therapy.

    8. 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.

    9. Use of rifampin within 2 weeks prior to Day 1 or planned during the trial.

    10. Malignant condition in the past 5 years (except successfully treated basal/squamous cell carcinoma of the skin or cervical cancer in situ).

    11. 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.

    12. 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.

    13. 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.

    14. Previous enrollment in this trial or participation in a prior HZN-825 or SAR100842 clinical trial.

    15. Known history of positive test for human immunodeficiency virus.

    16. 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).

    17. Current alcoholic liver disease, primary biliary cirrhosis or primary sclerosing cholangitis.

    18. Previous organ transplant (including allogeneic and autologous marrow transplant).

    19. International normalized ratio >2, prolonged prothrombin time >1.5 × the upper limit of normal (ULN) or partial thromboplastin time >1.5 × ULN at Screening.

    20. Alanine aminotransferase or aspartate aminotransferase >2.0 × ULN.

    21. Estimated glomerular filtration rate <30 mL/min/1.73 m2 at Screening.

    22. Total bilirubin >2 × ULN. Subjects with documented diagnosis of Gilbert's syndrome may be enrolled if their total bilirubin is ≤3.0 mg/dL.

    23. Moderate (Child-Pugh B) to severe (Child-Pugh C) hepatic impairment according to the Child-Pugh scoring system.

    24. Any verified Grade 4 laboratory abnormality.

    25. Any acute laboratory abnormality at Screening that, in the opinion of the Investigator, would preclude the subject's participation in the trial.

    26. 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.

    27. Any other condition that, in the opinion of the Investigator, would preclude enrollment in the trial.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama at Birmingham Birmingham Alabama United States 35233
    2 Palmtree Clinical Research Palm Springs California United States 92262
    3 St. Francis Medical Institute Clearwater Florida United States 33765
    4 Advanced Pulmonary Research Institute Loxahatchee Groves Florida United States 33470
    5 Central Florida Pulmonary Group PA Orlando Florida United States 32803
    6 DBC Research Corp. Tamarac Florida United States 33321
    7 University of Kansas Medical Center Kansas City Kansas United States 66160
    8 Nebraska Pulmonary Specialties LLC Lincoln Nebraska United States 68510
    9 Dartmouth Hitchcock Medical Center Lebanon New Hampshire United States 03756-1000
    10 Clinical Research of Gastonia Gastonia North Carolina United States 28054
    11 Shelby Clinical Research Shelby North Carolina United States 28150
    12 Thomas Jefferson University Philadelphia Pennsylvania United States 19107
    13 Clinical Research of Rock Hill Rock Hill South Carolina United States 29732
    14 Clinical Trials Center of Middle Tennessee Franklin Tennessee United States 37067
    15 El Paso Pulmonary Association - Elligo El Paso Texas United States 79902-1124
    16 Metroplex Pulmonary and Sleep Medicine Center McKinney Texas United States 75069
    17 Instituto De Enfermedades Respiratorias E Investigacion Medica Florencio Varela Buenos Aires Argentina 1888
    18 Instituto Ave Pulmo Mar Del Plata Buenos Aires Argentina 7600
    19 Instituto De Patologías Respiratorias San Miguel De Tucumán Tucumán Argentina 4000
    20 Centro Medico Dra de Salvo Ciudad de Buenos Aires Argentina C1426ABP
    21 Instituto Del Buen Aire Santa Fe Argentina 3000
    22 Royal Adelaide Hospital Adelaide South Australia Australia 5000
    23 Box Hill Hospital Box Hill Victoria Australia 3128
    24 Centro de Investigación Curico Curico Maule Chile 3440000
    25 Enroll SpA Providencia Región-MetropolitanadeSantiago Chile 7500587
    26 Meditek Ltda Santiago Región-MetropolitanadeSantiago Chile 8330008
    27 MIRES/MYF estudios cli-nicos Ñuñoa Región-MetropolitanadeSantiago Chile 7750495
    28 Centro Respiratorio Integral LTDA. (CENRESIN) Quillota Valparaíso Chile 2260000
    29 Centro de Investigacion del Maule Talca Chile 3465586
    30 Clinical Research Chile SpA Valdivia Chile 8330033
    31 Hopital Nord AP-HM Marseille Bouches-du-Rhône France 13915
    32 Hopital Haut Leveque Pessac Gironde France 33604
    33 Hôpital Bretonneau Tours Indre-et-Loire France 37044
    34 University General Hospital of Patras Patras Achaïa Greece 265 04
    35 Athens Medical Center Marousi Attiki Greece 151 25
    36 University General Hospital of Ioannina Ioannina Greece 455 00
    37 University General Hospital of Heraklion Iraklio Greece 711 10
    38 University General Hospital of Larissa Larisa Greece 411 10
    39 Azienda Ospedaliera Universitaria Senese Siena Italy 53100
    40 Seoul National University Bundang Hospital Seongnam-si Gyeonggido Korea, Republic of 13620
    41 Korea University Anam Hospital Seoul Korea, Republic of 02841
    42 Asan Medical Center Seoul Korea, Republic of 05505
    43 Samsung Medical Center Seoul Korea, Republic of
    44 Oaxaca Site management Organization (OSMO) Centro Oaxaca Mexico 68000
    45 Erasmus MC Rotterdam Netherlands 3015 GD
    46 KwaPhila Health Solutions Durban Kwazulu - Natal South Africa 4091
    47 Dr. Ismail Abdullah Private Practice Cape Town Western Cape South Africa 7764
    48 Hospital Universitario de Bellvitge L'Hospitalet De Llobregat Barcelona Spain 08907
    49 Hospital Universitario Quironsalud Madrid Pozuelo De Alarcón Madrid Spain 28223
    50 Hospital Universitario 12 de Octubre Madrid Spain 28041
    51 Kaohsiung Medical University - Chung-Ho Memorial Hospital Kaohsiung City Taiwan 807

    Sponsors and Collaborators

    • Horizon Therapeutics Ireland DAC

    Investigators

    • Study Director: Farah Ali, MD, Horizon Therapeutics

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Horizon Therapeutics Ireland DAC
    ClinicalTrials.gov Identifier:
    NCT05032066
    Other Study ID Numbers:
    • HZNP-HZN-825-303
    • 2021-001253-32
    First Posted:
    Sep 2, 2021
    Last Update Posted:
    Aug 25, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Horizon Therapeutics Ireland DAC
    Pulmonary Fibrosis
    Additional relevant MeSH terms:
    Pulmonary Fibrosis
    Idiopathic Pulmonary Fibrosis
    Fibrosis

    Study Results

    No Results Posted as of Aug 25, 2022