AXATILIMAB for Idiopathic pulmonary fibrosis

Inclusion criteria

• {"criterion_text":"- 1.\tMale or female subject aged ≥40 years on the day of signing the Informed Consent Form (ICF).\n- 10. Subject is capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.\n- 11. Subject and Investigator considered all medicinal treatment options and/or possibly lung transplantation prior to considering participation in the study.\n- 2. Documented diagnosis of IPF per the 2018 American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Society Clinical Practice Guideline (Raghu 2018).\n- 3. HRCT confirming the diagnosis of IPF based on radiographic findings, as follows: Chest HRCT performed within 12 months prior to Screening Visit 1 and according to the minimum requirements for IPF diagnosis by central review based on subject's HRCT only (if no lung biopsy is available) or based on both HRCT and lung biopsy (with application of the different criteria in either situation). If an evaluable HRCT <12 months prior to Screening is not available, an HRCT can be performed at Screening Visit 1 to determine eligibility, according to the same requirements as the historical HRCT. If a subject has an indeterminate usual interstitial pneumonia (UIP) pattern and their HRCT is >6 months old, if in the opinion of the Investigator their disease has progressed, an additional HRCT may be obtained and reviewed for eligibility.\n- 4. Subjects are eligible if they meet either of the following criteria: a. UIP or probable UIP pattern determined by at least 2 reviewers (see Appendix 3), or b. Indeterminate UIP with an accompanying biopsy supporting UIP or probable UIP histopathology pattern. The pathology report from a locally certified pathologist will provide documentation of histopathologic criteria (see Appendix 3).\n- 5. Meeting one of the following criteria for background IPF medication use: a.\tSubjects may be treatment-naïve to nintedanib or pirfenidone for reasons such as contraindication to nintedanib or pirfenidone or subject refusal. (Note: Initiation of nintedanib or pirfenidone and consideration of other therapies for IPF should be discussed by Investigator before study enrollment.) b.\tSubjects receiving pirfenidone or nintedanib for IPF must have been at a stable dose for at least 12 weeks before Screening. c.\tIf subjects have previously taken and discontinued nintedanib or pirfenidone for any reason (eg, side effect, no therapeutic benefit, refusal of these medications by the subject), they must have discontinued such treatment ≥4 weeks prior to Screening Visit 1. Note: Discontinuation of nintedanib or pirfenidone for the sole purpose of enrollment in this study is not allowed.\n- 6.\tMeeting all of the following criteria during the Screening Period: a.\tFVC ≥45% of predicted normal at Screening Visit 1 or Visit 2, (optional if Screening Visit 1 occurred between 6 AM and 12 PM and the subject meets the PFT criteria in this inclusion criterion #6) b.\tForced expiratory volume in 1 second (FEV1)/FVC ≥0.7 or ≥ age-adjusted lower limit of normal Global Lung Function Initiative (GLI) values (Quanjer et al, 2012) at Screening Visit 1 or Visit 2, (optional, as above) c.\tDLCO ≥30% and ≤90% of predicted, corrected for hemoglobin at Screening Visit 1, d.\tAcceptability: Subject can perform acceptable PFTs (ie, meet ATS/ERS acceptability criteria [Appendix 2] at Screening Visits 1, 2, (optional, as above), and 3). e.\tRepeatability: Subject can perform technically acceptable PFTs meeting repeatability criteria for FVC at Screening Visits 1, 2, (optional, as above), and 3 (Appendix 2).\n- 7. Estimated minimum life expectancy of at least 12 months for non-IPF-related disease in the opinion of the Investigator.\n- 8. Male subjects and female subjects of childbearing potential (defined as females who are fertile, following menarche and until becoming post-menopausal unless permanently sterile) agree to use highly effective contraception measures from the time of first dose of study drug (for the male subject) or the signing of the ICF (for the female subject), during the study, and until 90 days after the last dose of study drug. Subjects agree not to donate eggs or sperm during the same period. Male subjects must use a condom and female partners of male subjects who are of childbearing potential must use a highly effective method of contraception, defined below: a.\tA highly effective method of contraception is one that results in a low failure rate (ie, <1% per year) when used consistently and correctly. The acceptable methods of contraception include: sexual abstinence (defined as refraining from heterosexual intercourse during the entire treatment and follow-up periods), a vasectomized partner, bilateral tubal occlusion, any effective intrauterine device/hormone-releasing system, and progesterone-only (oral, injectable, or implantable) or combined (estrogen- and progesterone-containing; oral, intravaginal, or transdermal) hormonal contraception associated with inhibition of ovulation. Note: Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method are not acceptable methods of contraception. b.\tThe efficacy of oral hormonal contraceptives may be compromised by vomiting and/or diarrhea or other conditions where the drug absorption may be reduced. Advise women taking oral hormonal contraceptives experiencing these conditions to use alternative highly effective contraception.\n- 9. Subject, according to the Investigator’s best judgment, can comply with the requirements of the protocol."}

Exclusion criteria

• {"criterion_text":"- 1.\tHistory of malignancy within the past 5 years unless previously treated with curative intent and approved by Medical Monitor (e.g. carcinoma in situ of the uterine cervix, basal cell carcinoma of the skin that has been treated with no evidence of recurrence, low risk prostate cancer [confined to prostate] that has been managed medically through active surveillance or watchful waiting or definitively treated more than 12 months ago with no evidence of recurrence, squamous cell carcinoma of the skin if fully resected, non-invasive ductal carcinoma in situ of the breast, and melanoma in situ).\n- 10. Acute respiratory or systemic bacterial, viral, or fungal infection requiring systemic treatment either during Screening or prior to Screening and not successfully resolved 4 weeks prior to Screening Visit 1.\n- 11. Class IV New York Heart Association chronic heart failure.\n- 12. Significant pulmonary hypertension (PH) defined by any of the following: a. Previous clinical or echocardiographic evidence of significant right heart failure b. History of right heart catheterization showing a cardiac index ≤2 L/min/m² c. PH requiring parenteral therapy with epoprostenol/treprostinil\n- 13. Cardiopulmonary rehabilitation program based on exercise training that has been completed within 6 weeks prior to Screening or planned to start within the first 6 weeks of the subject's enrollment in this study.\n- 14. History of cigarette smoking or vaping within the previous 3 months.\n- 15. Recent history (<6 months) of alcohol or substance abuse disorder.\n- 16. Unstable cardiovascular, pulmonary (other than IPF), or other disease within 6 months prior to Screening or during the Screening Period (eg, acute coronary disease, heart failure, and stroke).\n- 17. Major surgery within 3 months prior to Screening, during screening or have major surgery planned during the study period.\n- 18.\tAlanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >2 x upper limit of normal (ULN) or total bilirubin ≥1.5 x ULN. Retesting is allowed once.\n- 19. Moderate to severe hepatic impairment (Child-Pugh B or C).\n- 2. Abnormalities detected on ECG of either rhythm or conduction that in the opinion of the Investigator are clinically significant. Note: • Subjects with implantable cardiovascular devices (eg, pacemaker) affecting the QT interval time may be enrolled in the study based upon Investigator judgment following cardiologist consultation if deemed necessary. • Atrial fibrillation that has been clinically stable for at least 6 months and that has been appropriately treated with anticoagulants and controlled with a rate control strategy (eg, selective beta blocker, calcium channel blocker, digoxin or ablation therapy) for at least 6 months is allowed for inclusion. In such subjects, if atrial fibrillation is present at Visit 1, resting ventricular rate must be <100 beats per minute.\n- 20. Amylase or lipase >1.5 x ULN; creatine phosphokinase (CPK) >2 x ULN. Retesting is allowed once.\n- 21. Abnormal renal function defined as estimated creatinine clearance of <30 mL/min, calculated according to the Chronic Kidney Disease Epidemiology Collaboration formula (Inker 2021). Retesting is allowed once.\n- 22. History of acute pancreatitis in the prior 12 months or ≥2 episodes in past 3 years.\n- 23. Subject with acquired immune deficiency syndrome.\n- 24. A history of tuberculosis in the prior 6 months, or subjects with active or latent tuberculosis, confirmed by a positive test during Screening (interferon gamma release assay). [The interferon gamma release assay may be substituted with local tuberculosis test or local tuberculosis test results determined within 6 months prior to Screening Visit 1.]\n- 25. An active coronavirus disease 19 (COVID-19) infection within 4 weeks prior to Screening.\n- 26. Hepatitis B (defined as hepatitis B virus [HBV] surface antigen positive and HBV core antibody positive, with positive HBV deoxyribonucleic acid [DNA], or HBV positive core antibody alone with positive HBV DNA. Hepatitis C (defined as positive hepatitis C [HCV] antibody with positive HCV ribonucleic acid [RNA]).\n- 27. Female subject who is pregnant or breastfeeding.\n- 28. Previous exposure to study intervention or known allergy/sensitivity to study drug and/or its excipients.\n- 29.\tReceiving an investigational non-biologic treatment within 28 days before randomization or receiving an investigational biologic treatment within 28 days or 5 half-lives of randomization, whichever is longer. Any AE related to prior investigational biologic treatment must have resolved to baseline severity or ≤ Grade 1.\n- 3. Emphysema present on ≥50% of the HRCT, or the extent of emphysema is greater than the extent of fibrosis, according to central review of the HRCT.\n- 30. Inadequate IV access.\n- 31. Positive for human immunodeficiency virus (HIV) antibodies.\n- 4. Interstitial lung disease associated with known primary diseases (eg, connective tissue disease, sarcoidosis and amyloidosis), exposures (eg, radiation, silica, asbestos, and coal dust), or drugs (eg, amiodarone).\n- 5.\tSubjects who cannot meet protocol-specified baseline stability criteria. Forced vital capacity baseline stability is defined as the FVC assessments at Visit 4 (Week 0/Day 1/Randomization) being within ±15% of the mean of the FVC assessments obtained at 2 preceding screening visits. At Visit 4, if the pre-dose FVC is outside of ±15% range, the subject will not be randomized and will be considered a screen failure.\n- 6. Acute IPF exacerbation within 3 months prior to screening. The definition of an acute IPF exacerbation is as follows: Previous or concurrent diagnosis of IPF; Acute worsening or development of dyspnea typically <1-month duration; Computed tomography with new bilateral ground-glass opacity and/or consolidation superimposed on a background pattern consistent with usual interstitial pneumonia pattern and deterioration not fully explained by cardiac failure, fluid overload or by a defined cause.\n- 7. Receiving nintedanib in combination with pirfenidone.\n- 8. Receiving systemic corticosteroids equivalent to prednisone >10 mg/day or equivalent within 2 weeks prior to Screening.\n- 9. Use of any of the following therapies within 4 weeks prior to Screening and during the Screening Period, or planned during the study: imatinib, ambrisentan, azathioprine, mycophenolate mofetil, cyclophosphamide, cyclosporine A, tacrolimus, bosentan, methotrexate, inhaled treprostinil, phosphodiesterase-5 inhibitors, including sildenafil (unless for occasional use), prednisone at steady dose >10 mg/day or equivalent, or other investigational therapy."}

Primary endpoints

• {"endpoint_text":"- The annualized rate of decline in morning pre dose trough forced vital capacity (FVC) (mL) over 26 weeks","definition_or_measurement_approach":"Annualized rate of decline in morning pre-dose trough forced vital capacity (FVC) measured in mL over a 26-week treatment period (morning pre-dose trough FVC assessments)."}

Secondary endpoints

• {"endpoint_text":"- Time to disease progression. Disease progression is defined as absolute FVC percent predicted decline of ≥10%, or occurrence of lung transplant or all-cause death prior to Week 26.","definition_or_measurement_approach":"Time from baseline to disease progression as defined by an absolute FVC percent predicted decline ≥10%, lung transplant, or all-cause death before Week 26."}
• {"endpoint_text":"- The annualized rate of decline in FVC percent predicted over 26 weeks.","definition_or_measurement_approach":"Annualized rate of decline in FVC percent predicted measured over 26 weeks."}
• {"endpoint_text":"- Change in St. George’s Respiratory Questionnaire (SGRQ) from baseline to Week 26.","definition_or_measurement_approach":"Mean change from baseline to Week 26 in SGRQ scores."}
• {"endpoint_text":"- The mean change in diffusion capacity for carbon monoxide (DLCO % of predicted, corrected for hemoglobin) from baseline to Week 26.","definition_or_measurement_approach":"Mean change from baseline to Week 26 in DLCO percent predicted, corrected for hemoglobin."}

Methods

• Dear Doctor letters to referring physicians (country-specific versions present e.g., ES, BE, CZ, IT).
• Study guides and study handouts for HCPs/sites (Study Guide documents; country-specific versions).
• Patient handouts/leaflets and study guides for potential participants (K2 handout; country-specific versions).
• Local site recruitment arrangements documents (K1_Recruitment arrangements) provided per country.

Spain

Earliest CTIS Part Ii Submission Date

20-12-2023

Latest Decision Or Authorization Date

15-04-2026

Processing Time Days

847

Number Of Sites

15

Number Of Participants

24

Belgium

Earliest CTIS Part Ii Submission Date

30-05-2024

Latest Decision Or Authorization Date

01-04-2026

Processing Time Days

670

Number Of Sites

3

Number Of Participants

10

Czechia

Earliest CTIS Part Ii Submission Date

08-05-2024

Latest Decision Or Authorization Date

17-03-2026

Processing Time Days

678

Number Of Sites

1

Number Of Participants

5

Germany

Earliest CTIS Part Ii Submission Date

29-05-2024

Latest Decision Or Authorization Date

11-03-2026

Processing Time Days

651

Number Of Sites

7

Number Of Participants

32

France

Earliest CTIS Part Ii Submission Date

27-05-2024

Latest Decision Or Authorization Date

02-04-2026

Processing Time Days

675

Number Of Sites

7

Number Of Participants

20

Italy

Earliest CTIS Part Ii Submission Date

20-12-2023

Latest Decision Or Authorization Date

27-04-2026

Processing Time Days

859

Number Of Sites

10

Number Of Participants

24

Romania

Earliest CTIS Part Ii Submission Date

05-06-2025

Latest Decision Or Authorization Date

20-04-2026

Processing Time Days

319

Number Of Sites

2

Number Of Participants

12

Poland

Earliest CTIS Part Ii Submission Date

14-05-2024

Latest Decision Or Authorization Date

20-04-2026

Processing Time Days

706

Number Of Sites

4

Number Of Participants

14

Primary sponsor

Full Name

Syndax Pharmaceuticals Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Ppd Inc.

Responsibilities

code:8

Name

Syneos Health Netherlands B.V.

Responsibilities

codes: 1,12,2,5

Name

Icon Development Solutions LLC

Responsibilities

code:4

Third parties

• {"country":"United States","full_name":"Rules Based Medicine Inc.","duties_or_roles":"code:4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Ppd Inc.","duties_or_roles":"code:8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Transperfect Translations International Inc.","duties_or_roles":"value: eTMF","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Syneos Health Netherlands B.V.","duties_or_roles":"codes: 1,12,2,5","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Vitalograph Limited","duties_or_roles":"value: ECG, 6MWT, DLCO & Spirometry","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"value: HRCT overread","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Devpro Biopharma LLC","duties_or_roles":"codes: 11,12,13,5,9","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Packaging Coordinators LLC","duties_or_roles":"code:14","organisation_type":"Pharmaceutical company"}
• {"country":"Canada","full_name":"Everest Clinical Research Corporation","duties_or_roles":"codes:10,3,6,7","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Acm Medical Laboratory Inc.","duties_or_roles":"code:4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Netherlands","full_name":"Pharmaceutical Research Associates Group B.V.","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Trial By Fire Solutions LLC","duties_or_roles":"value: CTMS","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Icon Development Solutions LLC","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Biologics Development Services LLC","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Azenta US Inc.","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"The Doctors Laboratory Limited","duties_or_roles":"code:4","organisation_type":"Laboratory/Research/Testing facility"}