A Study to Evaluate the Efficacy, Safety and Tolerability of HZN-825 in Subjects with Idiopathic Pulmonary Fibrosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Horizon Therapeutics Ireland Designated Activity Company

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

11 May 2022 → 2 Jan 2025

Decision date (initial)

2024-05-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Horizon Therapeutics USA, Inc

External identifiers

EU CT number

2023-509784-24-00

EudraCT number

2021-001253-32

ClinicalTrials.gov

NCT05032066

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Pharmacokinetic, Pharmacodynamic, Efficacy, Pharmacogenetic, Dose response, Therapy

Part 1 (Core Phase): The primary objective is to demonstrate the efficacy of 2 dose regimens of HZN-825 versus placebo in subjects with IPF, as determined by a comparison of change in forced vital capacity (FVC) % predicted after 52 weeks of treatment.

Part 2 (Extension Phase): The primary efficacy objective is to assess the efficacy of HZN 825 in subjects with IPF after 52 weeks of open label treatment

Secondary objectives 1

1. Core Phase: 1.Evaluate the effect of 2 dose regimens of HZN-825 vs Placebo on subjects with decline in FVC% predicted ≥10% from Baseline after 52 w of treatment 2.Evaluate the effect of 2 dose regimens of HZN-825 vs Placebo on the changes from Baseline in the 6MWT after 52 w of treatment 3.Evaluate the effect of 2 dose regimens of HZN-825 vs Placeboon the K-BILD after 52 w of treatment 4.Evaluate the effect of 2 dose regimens of HZN-825 vs Placebo on the L-IPF after 52 w of treatment. 5.Evaluate the effect of 2 dose regimens HZN-825 vs Placebo on the LCQ after 52 w of treatment. 6.Evaluate the effect of 2 dose regimens of HZN-825 vs Placebo on the rate of hospitalization due to respiratory distress up to 52 w of treatment. 7.Evaluate the effect of 2 dose regimens of HZN-825 vs Placebo on the composite endpoint of PFS, where progression includes decline in FVC% predicted ≥10% from Baseline or death over 52 wks of treatment. 8.Assess safety and tolerability of PR1 based on AEs,SAEs and AESI 9.Evaluate the PK of HZN-825

Conditions and MedDRA coding

Idiopathic Pulmonary Fibrosis

Study design 1 period

Regulatory references

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Core Phase: 1. Written informed consent. 2. Male or female ≥18 years of age at Screening. 3. Current diagnosis of IPF, as defined by American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Society (ALAT) guidelines [Raghuet al., 2022] and determined by central review; the date of initial diagnosis of IPF should be ≤7 years prior to Screening. 4. No recent changes or planned changes to the dose or regimen for IPF therapy, defined as: • Receiving a stable dose of IPF-approved therapy (i.e., nintedanib or pirfenidone) for a minimum of 3 months prior to Day 1 with no plans to change the background regimen during trial participation, or • Not currently receiving background IPF-approved therapy at Screening (either naïve to IPF-approved therapy or previously discontinued any IPF-approved therapy at least 4 weeks prior to Day 1 or drug-specific, 5 half-lives elimination period if longer than 4 weeks), and with no current plans to restart treatment during trial participation • Subjects receiving any additional agent for IPF therapy must be on a stable regimen for at least 3 months prior to Day 1 with no current plans to change the treatment regimen during trial participation. Any previously discontinued therapy used to treat IPF must have been discontinued at least 4 weeks prior to Day 1 or 5 half-lives for that specific therapy must have elapsed, whichever is longer, with no plans to restart the therapy during trial participation. 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. The HRCT must demonstrate a usual interstitial pneumonia or probable usual interstitial pneumonia pattern based on central review vendor interpretation. Histopathology in combination with HRCT results supportive of an IPF or IPF likely diagnosis according to Raghu et al., 2022 can be submitted to support subject eligibility. 6. HRCT shows ≥10% to <50% parenchymal fibrosis (reticulation) 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, as determined by central review: a. FVC ≥45% predicted of normal b. forced expiratory volume in 1 second (FEV1)/FVC ≥0.7 c. DLCO corrected for hemoglobin is ≥25% and ≤90% predicted of normal 8. Estimated minimum life expectancy of ≥30 months for non-IPFrelated disease, in the opinion of the Investigator. 9. Vaccinations are up to date, according to the Investigator's discretion, given age, comorbidities 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. Extension Phase: 1. Written informed consent. 2. Completed the Double-blind Treatment Period (Week 52) of the Core Phase of the trial; subjects prematurely discontinued from trial drug in the Core Phase of the trial for reasons other than safety or tolerability may be included at the discretion of the Investigator after completing scheduled visits, including Week 52 assessments. 3. Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the Extension Phase of the trial.

Exclusion criteria 1

1. Core Phase: 1. Any of the following cardiovascular diseases: a. uncontrolled, severe hypertension (≥160/100 mmHg), within 6 months of Screening b. myocardial infarction within 6 months of Screening c. unstable cardiac angina within 6 months of Screening 2. Interstitial lung disease (ILD) associated with known primary diseases, connective tissue disorders, exposures or drugs. 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. Prednisone ≤10 mg/day (or equivalent dosing of glucocorticoids) is allowed. Change in regimen or dosage of any 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 4 weeks after last dose of trial drug. Fertile male subjects must use a condom throughout the trial and for 4 weeks after the last dose of trial drug. 9. Pregnant or lactating women and women who plan to become pregnant or breast feed during the trial and within 4 weeks 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 (HIV). 13. Active hepatitis (any of the following at Screening): Hepatitis B: •positive hepatitis B surface antigen •positive for anti-hepatitis B core antibody (anti HBcAb) and a positive test for hepatitis B surface antibody (HBsAb) and presence of hepatitis B virus DNA •positive for HBcAb and a negative test for HBsAb and presence of hepatitis B virus DNA Hepatitis C: •positive anti hepatitis C virus (anti HCV) and positive HCV RNA. 14. Current alcoholic liver disease, primary biliary cirrhosis or primary sclerosing cholangitis. 15. Previous organ transplant (including allogeneic and autologous marrow transplant). **Please refer to protocol section 9.3.1 and 9.3.2. Extension Phase: 1.Anticipated use of another investigational agent for any condition during the course of the trial. 2.New diagnosis of malignant condition after enrolling in Trial HZNPHZN-825-303 (except successfully treated basal/squamous cell carcinoma of the skin or cervical cancer in situ). 3.Estimated minimum life expectancy ≤18 months, in the opinion of the Investigator. 4.WOCBP or male subjects not agreeing to use highly effective method(s) of birth control throughout the Extension Phase and for 4 weeks after last dose of HZN-825. 5.Pregnant or lactating women. 6.Any other new development of the disease/condition/significant laboratory test abnormality during the course of the Core Phase of the trial, in the opinion of the Investigator, that would potentially put the subject at unacceptable risk. 7.In the opinion of the Investigator, unlikely to comply with the trial protocol or has a concomitant disease or condition that could interfere with the conduct of the trial.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Core Phase: Change in FVC % predicted from Baseline to Week 52. Extension Phase: Change from both Baselines in FVC % predicted at Week 104.

Secondary endpoints 1

1. Core Phase: 1. Proportion of subjects with decline in FVC % predicted ≥10% from Baseline at Week 52. 2. Change from Baseline in the 6MWT results to Week 52. 3. Change from Baseline in K-BILD scores to Week 52. 4. Change from Baseline in L-IPF scores to Week 52. 5. Change from Baseline in LCQ scores to Week 52. Please refer to protocol section 8.1.2 and 8.2.2 for details

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Horizon Therapeutics Ireland Designated Activity Company

Sponsor organisation

Horizon Therapeutics Ireland Designated Activity Company

Address

70 Saint Stephen's Green

City

Dublin 2

Postcode

D02 E2X4

Country

Ireland

Scientific contact point

Organisation

Horizon Therapeutics Ireland Designated Activity Company

Contact name

Brajesh Pandey

Public contact point

Organisation

Horizon Therapeutics Ireland Designated Activity Company

Contact name

Brajesh Pandey

Third parties 8

Locations

6 EU/EEA countries · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 27 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications