A Study to Evaluate the Safety and Pharmacokinetic Properties of LASN01 in Healthy Subjects and in Patients With Pulmonary Fibrosis or Thyroid Eye Disease

A Study to Evaluate the Safety and Pharmacokinetic Properties of LASN01 in Healthy Subjects and in Patients With Pulmonary Fibrosis or Thyroid Eye Disease

A Phase 1, Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose Study to Determine the Safety, Tolerability, Immunogenicity and Pharmacokinetic Properties of LASN01 in Healthy Subjects and in Patients With Pulmonary Fibrosis or Thyroid Eye Disease

LASN01 is a novel, fully human antibody directed against the human IL-11 receptor being developed for fibrosis. This study is a four-part trial consisting of Parts A, B, C and D. The primary objective of this study is to evaluate the safety, tolerability, and the secondary objective is to evaluate the immunogenicity and pharmacokinetics of single and multiple doses of LASN01 in healthy participants and in patients with idiopathic pulmonary fibrosis (IPF) or progressive fibrosing interstitial lung disease (PF-ILD) or Thyroid Eye disease (TED).

This clinical trial (LASN01-CL-001) consists of 4 parts, each part containing adaptive design elements that can be modified. Part A will comprise a single-dose administration in healthy participants in 5 dose cohorts. Part B will comprise a multiple-dose administration in healthy participants in 2 dose cohorts. Part C will comprise a multiple-dose administration in a single cohort of approximately 8 to 12 participants. Part D will comprise a multiple-dose design in a single cohort of approximately 8 to 12 participants. In each part of the study, participants will be randomized to receive IV doses of LASN01 or placebo.

Part A (SAD in healthy subjects) Part B (MAD in healthy subjects) Part C (Patients with IPF or PF-ILD) Part D (Patients with Thyroid Eye disease)

Part A (SAD in healthy subjects) Part B (MAD in healthy subjects) Part C (Patients with IPF or PF-ILD) Part D (Patients with Thyroid Eye disease)

Number of participants with abnormal clinically significant 12-lead electrocardiogram (ECG) parameters

PK parameter assessed by serum LASN01 concentration at specified timepoints for maximum plasma concentration (Cmax)

PK parameter assessed by serum LASN01 concentration at specified timepoints for time to peak concentration (T max)

PK parameter assessed by serum LASN01 concentration at specified timepoints for area under curve (AUC)

PK parameter assessed by serum LASN01 concentration at specified timepoints for clearance volume (CL)

PK parameter assessed by serum LASN01 concentration at specified timepoints for terminal phase volume (Vz)

I. Participant Inclusion Criteria- Parts A, B, C, and D Participants who are women of child-bearing potential (WOCBP) with male partners and WOCBP partners of male participants must be nonpregnant, nonlactating, and use 2 effective methods of contraception or a highly effective method of contraception Able to comprehend and willing to sign an ICF and understand and comply with the requirements of the study. Part A and Part B only Males or females, 18 through 60 years of age, inclusive Body weight ≥110 pounds (≥50 kg); body mass index (BMI) within the range of 18 through 32.0 kg/m2 In good health as determined by the Investigator Clinical laboratory evaluations within the reference range for the test laboratory, unless deemed not clinically significant by the Investigator Part C only Male and female patients >40 years of age (IPF patients) or ≥21 years of age (PF-ILD patients) IPF-specific Inclusion Criteria: As determined by the PI, a diagnosis of IPF in accordance with the 2018 American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Society Clinical Practice Guideline on Diagnosis of IPF (Raghu 2018) IPF has, in the opinion of the Investigator, been stable for ≥3 months at Screening PF-ILD-specific Inclusion Criteria: Patients with physician diagnosed ILD who fulfill ≥1 of the following criteria for PF-ILD within 24 months of the Screening visit despite treatment with approved and/or unapproved medications used in clinical practice to treat ILD, as assessed by the Investigator Fibrosing lung disease on HRCT performed within 3 years of the Screening Visit meeting the following criteria based on site multidisciplinary team review. If an initial or repeat HRCT scan within a 12-month window is not available, a repeat HRCT scan will be obtained during Screening: Presence of HRCT pattern of usual interstitial pneumonia Presence of reticular abnormality with traction bronchiectasis Presence definite honeycomb lung destruction with basal and peripheral predominance Disease extent >10% of total lung parenchyma Absence of widespread consolidation or progressive massive fibrosis For patients with underlying CTD: stable CTD as defined by no initiation of new therapy or withdrawal of therapy for CTD within 6 weeks before the Screening visit FVC ≥45% predicted Part D only Age 18 through 80 years, inclusive Clinical diagnosis of Graves' disease associated with active TED Moderate-to-severe active TED Less than 12 months from onset of TED No previous: Medical treatment for TED, excluding local supportive measures, mycophenolate, and oral or injectable steroids if the maximum cumulative dose is ≤3g methylprednisolone or equivalent with ≥6 weeks between last administration of oral steroids and/or mycophenolate and Screening Surgical treatment in the study eye Orbital radiation II. Participant Exclusion Criteria Parts A, B, C, and D Positive polymerase chain reaction (PCR) test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at Screening or Day -1 or within 72 hours before randomization, or positive antigen test on Day -1 or Day 1, or acute infection with SARS-CoV-2 within last 3 months Any acute or chronic condition that, in the opinion of the Investigator, would limit the participant's ability to participate in and complete this clinical study Part A and Part B only Significant history or clinical manifestation of any significant endocrine, metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, or psychiatric disorder, as determined by the Investigator History of significant hypersensitivity; intolerance; or allergy to any drug compound, food, or other substance; or history of anaphylaxis or angioedema, as determined by the Investigator Any Screening laboratory evaluation outside the laboratory reference range except those the Investigator determines not to be clinically significant and laboratory tests for which limits are otherwise defined Positive serum test for HIV or hepatitis infection Currently receiving any antibiotics for upper or lower respiratory tract infections Use of any prescription drug or vaccine within 21 days before Check-in EXCEPTIONS: oral, implantable, transdermal, or injectable contraceptives, or NuvaRing® are permitted) EXCEPTIONS: killed and inactive vaccines, including mRNA vaccines (eg, pneumonia, influenza, SARS-CoV-2) and live attenuated vaccines (eg, varicella) are permitted, but should have been completed ≥14 days before Screening Any prescription biologic within 3 months or 5 half-lives (whichever is greater) before Check-in Participation in any other investigational study drug trial in which an investigational study drug was administered within 30 days before randomization or an investigational biological study drug was administered within 3 months before Check-in Part C only History of clinically relevant cardiovascular disease that could jeopardize a patient's health during the course of the study as determined by the Investigator Patients with concurrent active malignancy other than adequately treated basal cell carcinoma of the skin or carcinoma in situ of the cervix IPF-specific Exclusion Criteria: FVC <45% predicted of normal or a forced expiratory volume during the first second of the forced breath (FEV1)/FVC ratio of <0.7. Extent of emphysema in the lungs exceeds fibrosis, based on review of HRCT conducted within the last 3 years Currently receiving pirfenidone or nintedanib if on treatment for <3 consecutive months or needed dose modification due to AEs in the last 3 months PF-ILD-specific Exclusion Criteria: Diagnosis of IPF based on American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association 2018 Guidelines (Raghu 2018) Diagnosis of sarcoidosis Significant pulmonary arterial hypertension defined by any of the following: Previous clinical or echocardiographic evidence of significant right heart failure History of right heart catheterization showing a cardiac index ≤2 L/min/m² Pulmonary arterial hypertension requiring therapy with epoprostenol/treprostinil FVC <45% predicted of normal or a FEV1/FVC ratio of <0.7 Previous treatment with pirfenidone. Current or previous treatment with nintedanib is permissible in countries where it is approved for treatment of PF-ILD; patients currently being treated with nintedanib must be on stable treatment for ≥3 months with no change in dose during that period Part D only Any previous use of teprotumumab at any time; previous use of rituximab, tocilizumab, or any monoclonal antibody for immunomodulation within the past 9 months before randomization; or previous use of any other immunomodulating therapy within 3 months before randomization unless approved by the Medical Monitor. Patients with 2 mm proptosis decrease between Screening and Baseline, or a 1-point decrease on the CAS 7-point scale in any 2 weeks during the Screening period Patients with decreased best corrected visual acuity due to optic neuropathy as defined by a decrease in vision of 2 lines on the Snellen chart, new visual field defect, or color defect secondary to optic nerve involvement within the last 6 months before Screening