A study of efficacy and safety of various treatments in participants with idiopathic pulmonary fibrosis (IPF)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

25 Apr 2023 → 27 Sep 2024

Decision date (initial)

2024-03-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Novartis Pharma AG (OMS ID: ORG-100003911)

External identifiers

EU CT number

2023-508729-28-00

EudraCT number

2021-005066-17

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Others

The primary objective of this study is to assess the efficacy of the investigational products compared to placebo in participants with IPF measured by FVC expressed in percent predicted

Secondary objectives 7

1. To assess the efficacy of the investigational products, compared to placebo in participants with IPF measured by FVC expressed in mL.
2. To assess the impact of the investigational products on “progression-free survival (PFS)”
3. To assess the incidence of absolute decline in FVC ≥10% predicted
4. To assess the impact of the investigational products on pulmonary physiology
5. To assess the impact of the investigational products on exercise capacity
6. To assess the impact of the investigational products on patient reported outcome
7. To assess the safety and tolerability of the investigational products in participants with mild to moderate IPF

Conditions and MedDRA coding

Idiopathic pulmonary fibrosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Written informed consent must be obtained before any assessment is performed.
2. Male and female participants at least 40 years of age
3. IPF diagnosed based on ATS/ERS/JRS/ALAT IPF 2018 modified guideline for diagnosis and management, within 5 years of screening (HRCT and surgical lung biopsy or cryobiopsy (if available) will be read by a central reader)
4. FVC ≥45% predicted at screening with no clinically significant deterioration, as determined by investigator between the screening visit and randomization, as determined by the investigator.
5. DLCO, corrected for hemoglobin, ≥25% predicted (inclusive) at screening with no clinically significant deterioration, as determined by investigator between the screening visit and randomization, as determined by the investigator.
6. Unlikely to die from cause other than IPF within the next 2 years, in the opinion of the investigator
7. Unlikely to undergo lung transplantation during this trial in the opinion of the investigator
8. If a participant is taking nintedanib or pirfenidone, they must be on a stable regimen for at least 8 weeks prior to randomization
9. Able to communicate well with the investigator, to understand and comply with the requirements of the study

Exclusion criteria 30

1. Unable to perform PFTs, 6MWT or undergo HRCT procedure at time of screening
2. History of major organ, hematopoietic stem cell or bone marrow transplant
3. History of hypersensitivity to the study drug or to drugs of similar chemical classes in the cohort the participant is to be randomized
4. Serious local infection (e.g. cellulitis, abscess) or systemic infection that required hospitalization or was clinically significant in the opinion of the investigator, within 3 months prior to screening
5. Fever (body temperature >38 degrees Celsius) or symptomatic viral or bacterial infection within 2 weeks prior to screening or randomization • A known or suspected symptomatic Covid diagnosis within 3 months of screening visit or prior to randomization
6. History of primary or secondary immunodeficiency, including a positive human immunodeficiency virus (HIV) (enzyme-linked immunosorbent assay [ELISA] and western blot) test result
7. Current hepatitis C infection (defined as positive HCV antibody and detectable HCV ribonucleic acid [RNA]). Participants with positive HCV antibody and undetectable HCV RNA are eligible to participate in the study. Current hepatitis B infection (defined as positive for hepatitis B surface antigen [HBsAg] or positive anti-HBc with a negative anti-HBs). Participants with immunity to hepatitis B from previous natural infection (defined as negative HBsAg, positive anti-HBc, and positive anti-HBs) or vaccination (defined as negative HBsAg, negative anti-HBc, and positive anti-HBs) are eligible to participate in the study.
8. History of malignancy of any organ system (other than completely excised, localized carcinoma of the skin such as basal cell or squamous cell carcinoma or in situ cervical cancer), treated or untreated, within the past 5 years of screening, regardless of whether there is evidence of local recurrence or metastases
9. Significant cardiac disease (e.g. New York Heart Association Class 3 or 4; myocardial infarction within the past 6 months of screening; unstable angina; coronary angioplasty or coronary artery bypass graft within the past 6 months of screening; uncontrolled atrial or ventricular cardiac arrhythmias).
10. Pulmonary hypertension requiring pharmacologic treatment
11. Any surgical, medical (e.g. uncontrolled hypertension, diabetes), psychiatric or additional physical condition that the investigator feels may jeopardize the participant in case of participation in this study. The investigator should make this determination in consideration of the patient’s medical history and/or clinical or laboratory evidence of any of the following: • Moderate or severe hepatic failure (Child-Pugh classification stage B or C) • Significant renal impairment with an estimated glomerular filtration rate (eGFR) < 30 mL/min as calculated by the CKD-EPI formula
12. Inability to comply with study requirements.
13. Other unspecified reason that in the opinion of the investigator in consultation with the sponsor makes the participant unsuitable for enrollment
14. Active drug or alcohol abuse (as defined by the investigator) within 3 months prior to screening.
15. Use of any inhaled substance, including but not limited to tobacco or marijuana products and/ or the use of any electronic cigarette or vaping device, within 12 weeks prior to screening (note that respiratory inhalers or nebulizers for delivery of prescribed medication for pulmonary disease are allowed).
16. Any one of the following screening values of complete blood count laboratory values: • Hemoglobin levels < 10.0 g/dL • Total leukocyte count < 3,000/μL • Neutrophils <1.5 x 103 /μL • Platelets <100.0 x 103 /μL • Total Bilirubin > 1.5 mg/dL (in the absence of known Gilbert's syndrome) • Aspartate transaminase (AST) or alanine transaminase (ALT) > 2X upper limit of normal
17. Peripheral capillary oxygen saturation (SpO2) <90% at rest (if on supplemental oxygen, must be ≤2 L/min at rest)
18. Airway obstruction (i.e., prebronchodilator FEV1/ FVC < 0.7) or evidence of a bronchodilator response at screening as defined by an absolute increase of ≥12% and an increase of ≥ 200ml in FEV1 or FVC, or both, after bronchodilator use, compared with the values before bronchodilator use at screening.
19. Emphysema >20% on screening HRCT as assessed visually by central reader.
20. Fibrosis <10% on screening HRCT as assessed visually by central reader.
21. Clinical diagnosis of any connective tissue disease (including but not limited to scleroderma, polymyositis/ dermatomyositis, systemic lupus erythematosus, and rheumatoid arthritis) or a diagnosis of interstitial pneumonia with autoimmune features as determined by the investigator applying the recent ERS/ ATS research statement. Note: serological testing is not needed if not clinically indicated.
22. Other known causes of interstitial lung disease (e.g. domestic or occupational environmental exposures, drug toxicity) or another identifiable interstitial lung disease
23. Clinically diagnosed acute exacerbation of IPF (AE-IPF) or other significant clinical worsening within 3 months of randomization
24. Currently receiving high-dose corticosteroid, cytotoxic therapy (e.g. chlorambucil, azathioprine, cyclophosphamide, methotrexate), vasodilator therapy for pulmonary hypertension (e.g. bosentan), unapproved (e.g. IFN-γ, penicillamine, cyclosporine, mycophenolate, N-acetylcysteine [may vary by country]) and/or investigational therapy or device for IPF or administration of such therapeutics within 5 half-lives of the IP prior to initial screening in this study. A current dose of ≤5 mg/day of prednisone or its equivalent is acceptable if the dose is expected to remain stable during the study. (Note: N-Acetylcysteine used to treat cough is permissible).
25. Plan to enroll in another interventional trial while in this study
26. Blood donation of 1 unit (approximately 473mL) or more within 1 month prior to screening.
27. Male or female planning a pregnancy during the duration of this study. A serum pregnancy test will be performed on all female participants of childbearing potential.
28. Pregnant or nursing (lactating) women
29. Elective surgery planned to take place during this trial (excluding diagnostic procedures such as colonoscopy, etc.)
30. Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, unless they are using appropriate methods of contraception for 3 months prior to screening, during dosing, and for a period after stopping of investigational medication (any treatment specific contraception requirements and changes to duration or if WOCBP cannot be enrolled at all are outlined in Section 17).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline to end of treatment epoch (26 weeks of treatment) in Forced Vital Capacity (FVC) expressed in percent predicted

Secondary endpoints 7

1. Change from baseline to end of treatment epoch (26 weeks of treatment) in Forced Vital Capacity (FVC) expressed in mL
2. • Time to progression as defined by a composite endpoint including any of the following events: • Absolute reduction from baseline of ≥10% predicted in FVC • Nonelective hospitalization for respiratory events • Lung Transplant • Death
3. Number of participants with absolute decline of ≥10% predicted in FVC
4. Change from baseline to the end of treatment epoch (26 weeks of treatment) in DLCO absolute and percent predicted
5. Change from baseline to the end of treatment epoch (26 weeks of treatment) in 6-minute walk distance
6. Change from baseline to the end of treatment epoch (26 weeks of treatment) in scores from the L-IPF (Impacts and Symptoms Modules), K-BILD, Leicester cough, and R-Scale for PF questionnaires
7. Adverse Events, physical examinations, labs, ECGs, vital signs

Investigational products

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

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 15

Locations

4 EU/EEA countries · 12 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 4 · Art. 38 CTR

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 8 files

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

Application history

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