Principal Investigator: Mary  Scholand
Keywords: Pulmonary , IPF , Idiopathic Pulmonary Fibrosis , Anti-Inflammatory , Anti-Fibrotic , Fibrosis Department: Pulmonary
IRB Number: 00111783
Specialty: Pulmonary, Pulmonary, Pulmonary, Pulmonary
Sub Specialties: Advanced Lung Disease, Pulmonary Fibrosis, Pulmonary
Recruitment Status: Recruiting

Contact Information

Chloe Kirkpatrick

Simple Summary

To evaluate the Safety, Tolerability, Biological Activity, and PK of ND-L02-s0201 in Subjects With Idiopathic Pulmonary Fibrosis (IPF)

Detailed Description

This is a Phase 2, double-blind, placebo-controlled, randomized, multicenter, international study of 2 doses of ND-L02-s0201 for Injection to evaluate safety, tolerability, biological activity, and PK insubjects with a diagnosis of IPF with forced vital capacity (FVC) ≥ 45% of predicted and diffusion capacity of the lung for carbon monoxide (DLCO) ≥ 30% of predicted and who meet all inclusion criteria and do not meet any exclusion criteria.Two dose levels of ND-L02-s0201 will be evaluated: a low dose (45 mg) and a high dose (90 mg). Subjects will be randomly assigned to receive ND-L02-s0201 for Injection or placebo Q2W over a 24-week treatment period. Approximately 120 eligible subjects will be randomized 1:1:1 to 1 of3 treatment arms: ND-L02-s0201 for Injection high dose (90 mg), ND-L02-s0201 for Injection low dose (45 mg), or placebo.

Inclusion Criteria

To be randomized, all subjects must meet the criteria listed below. 

  1. Males and females between 40 and 80 years of age, inclusive, at the time of consent.
  2. Diagnosis of IPF within 5 years before Visit 1a, confirmed using modified American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Association (ALAT) consensus criteria (Raghu et al, 2011; see Section 11.2.5). 
  3. Interpretation of HRCT and, if performed, surgical lung biopsy (SLB) must be confirmed by the overreader.
  4. If available, chest HRCT performed within 6 months before Visit 1a will be submitted for overreader interpretation to determine the subject’s preliminary eligibility to participate in Screening.
  5. Overread of both historical (if applicable) and Visit 1b HRCT must support the “Diagnosis of IPF” based on the criteria outlined in Section 11.2.5.
  6. Extent of fibrosis greater than emphysema on HRCT determined by the overreader.
  7. If on pirfenidone or nintedanib, unchanged dose for at least 12 weeks before Visit 1a. Subjects may not be on both pirfenidone and nintedanib.
  8. Forced vital capacity (FVC) ≥ 45% of predicted. 
  9. Diffusion capacity of the lung for carbon monoxide (DLCO) corrected for hemoglobin ≥ 30% of predicted value.
  10. Pulse oximetry saturation 90%, at rest while breathing ambient air or ≤ 2 L/minute supplemental oxygen by nasal prongs/cannula (see Section 11.2.1). 
  11. Ratio of forced expiratory volume in 1 second (FEV1) to FVC ≥ 0.70.
  12. Adequate liver and renal function, as demonstrated by:
    • Total bilirubin ≤ 1.5 × upper limit of normal (ULN), unless participant has a documented history of Gilbert’s syndrome
    • Aspartate transaminase (AST) and alanine transaminase (ALT) < 2.5 × ULN
    • Creatinine < 2 × ULN
    • Serum albumin > 3.5 g/dL
  13. Life expectancy of 12 months. 
  14. Serum vitamin A level at Screening ≤ ULN of the central laboratory reference range.
  15. Women of childbearing potential (WCBP) must be willing to use a double-barrier method of contraception (eg, diaphragm with spermicide, condom with spermicide, tubal ligation) and either of the following methods of contraception throughout the study and study follow up or for at least 60 days after the last dose of study treatment:
    • Hormonal contraception (ie, injection, implant, pill, patch, or vaginal ring) in use for at least 30 days before administration of study treatment  or 
    • Intrauterine device in use for at least 30 days before administration of study treatment.

Note: A woman is considered to be of nonchildbearing potential if she meets one of the following criteria: a) has had at least 12 months of spontaneous amenorrhea; b) is at least 6 months postsurgical bilateral oophorectomy; or c) is at least 6 months postsurgical hysterectomy. Female subjects who meet criteria a) or b) must have serum follicle-stimulating hormone (FSH) levels > 40 IU/L to confirm nonchildbearing potential.

  1. Women must be willing not to breastfeed for 90 days after the last dose of the study drug.
  2. Males with female partners of childbearing potential must agree to use an effective barrier method of contraception (eg, condom with spermicide and contraception by female partner [see acceptable methods above]) from the first dose of study treatment until 90 days after the last dose of study treatment. All fertile men with female partners of childbearing potential will be instructed to contact the Investigator immediately if their partner becomes pregnant at any time during study participation. All men must agree not to donate semen from the first dose of study treatment until 90 days after the last dose of study treatment.
  3. Willing and able to provide written informed consent and comply with the study procedures and visit schedule, including follow-up visits.

Exclusion Criteria

Potential subjects who meet any of the following criteria at Screening will be excluded from the study:

  1. Best, acceptable FVC from separate Screening spirometry that differ by ≥ 200 mL.
  2. Respiratory exacerbation(s) or hospitalization for IPF exacerbation within 3 months before Visit 1a.
  3. Taking both pirfenidone and nintedanib concurrently within 12 weeks before Visit 1a.
  4. Anticipated to receive a lung transplant during the subject’s participation in the study.
  5. Diagnosis of any connective tissue disease with a natural history that may be associated with pulmonary disease.
  6. Clinical evidence of or known history of cirrhosis.
  7. History of osteomalacia, Paget’s disease of bone, jawbone necrosis, or a history of unexplained fractures, or fractures after minimal trauma, as determined by the Investigator.
  8. Uncontrolled cardiac disease or cardiac surgical procedure (eg, New York Heart Association Class III or IV, myocardial infarction, transient ischemic attack, uncontrolled atrial or ventricular cardiac arrhythmias, unstable angina, stroke, coronary angioplasty, coronary artery bypass graft) within 30 days before Visit 1a.
  9. Active smoker or smoking cessation within 12 weeks before Visit 1a.
  10. Malignancy within the last 5 years, with the exception of curable cancer (eg, basal or squamous cell skin cancer, cervical cancer in situ, nonmedullary thyroid carcinoma) who has received adequate treatment (eg, excision).
  11. Evidence of any unstable or untreated, clinically significant disease or condition that, in the opinion of the Investigator, might confound the interpretation of the study or place the subject at increased risk (eg, uncontrolled hypertension, diabetes mellitus). Subjects will have to have been on stable treatment for at least 4 weeks before Visit 1a.
  12. Treatment with high dose corticosteroids, cytotoxic agents (eg, chlorambucil, azathioprine, cyclophosphamide, methotrexate), unapproved IPF targeted therapy, and cytokine modulating agents within 8 weeks or 5 half-lives (whichever is longer) before Visit 1a. 
    1. A dose of ≤ 15 mg/day prednisone, or equivalent, is acceptable if unchanged for ≥ 10 weeks before Visit 1a and is expected to remain unchanged during the subject’s participation in the study.
  13. Participation in an investigational study with the last dose of investigational product occurring within 8 weeks or 5 half-lives (whichever is longer) before Visit 1a. 
  14. History of allergic reaction to any of the study drugs to be administered.
  15. Pregnant or breastfeeding.
  16. Veins unsuitable for repeated venipuncture or IV infusion (eg, veins that are difficult to locate, access, or puncture; veins with a tendency to rupture during or after puncture), in the opinion of study center personnel.
  17. Medical history of infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
  18. History of alcohol abuse and/or dependence within the last 2 years, as determined by the Investigator. 19. History within the last 2 years of significant mental illness, or physical dependence on any opioid or illicit drugs.
  19. 20. Suspected or confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, defined as meeting one or more of the following criteria:

    a. The subject has known exposure to a person with signs or symptoms of SARS-CoV-2 infection or has tested positive for SARS-CoV-2 (suggesting current infection) within 21 days prior to the subject’s Visit 1a.

    b. The subject has current signs and symptoms suggestive of SARS-CoV-2 infection.

    c. The subject has SARS-CoV-2 virus or viral antigen detected at Visit 1a using a test approved for marketing if testing is available. (Detection of antibody to SARS-CoV-2 will not be exclusionary. Refer to Section for more guidance on SARS-CoV-2 testing.)

Participant Reimbursement

$50.00 per visit