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

This randomized, placebo-controlled clinical trial (LASN01-CL-1101) consists of 4 parts, each part containing adaptive design elements that can be modified.

In Phase 1, Part A comprised of a single-dose administration in healthy participants in 5 dose cohorts and Part B comprised of a multiple-dose administration in healthy participants in 2 dose cohorts. Parts A&B have been completed.

In the Phase 2a portion, Part C comprised of a multiple-dose administration in a single cohort of patients with IPF and PF-ILD, and Part D comprised of a multiple-dose design in a single cohort of patients with TED.

In each part of the study, participants were randomized to receive IV doses of LASN01 or placebo.

I. Participant Inclusion Criteria-

Parts A, B, C, and D

• Female participants must be nonpregnant, nonlactating, and either postmenopausal for ≥12 months, surgically sterile for ≥6 months, or agree to use 2 effective methods of contraception or a highly effective method of contraception. Males must be surgically sterile for ≥6 months or agree to highly effective methods 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

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:

• A diagnosis of IPF
• IPF has 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.
• Fibrosing lung disease on HRCT performed within 3 years of the Screening Visit
• 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

• Male or female patients of age ≥18 years
• Clinical diagnosis of Graves' disease associated with active TED
• Moderate-to-severe active TED
• Less than 15 months from onset of TED in the study eye
• No previous medical treatment for TED with the exception of local supportive measures, mycophenolate and oral or injectable steroids, immunomodulating therapies, and/or orbital irradiation/radiotherapy

II. Participant Exclusion Criteria

Parts A, B, C, and D

• Any acute or chronic condition that 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
• History of significant hypersensitivity; intolerance; or allergy to any drug compound, food, or other substance; or history of anaphylaxis or angioedema
• 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 with the exception of hormonal contraceptives and vaccines.
• 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
• 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
• 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
• Diagnosis of sarcoidosis
• Significant pulmonary arterial hypertension
• FVC <45% predicted of normal or a FEV1/FVC ratio of <0.7
• Previous treatment with pirfenidone

Part D only

• Any previous use of anti-insulin-like growth factor 1 receptor monoclonal antibody (eg, teprotumumab) at any time
• 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, new visual field defect, or color defect secondary to optic nerve involvement within the last 6 months before Screening