Pulmonary Fibrosis, Thyroid Eye Disease
Conditions
Brief summary
LASN01 is a novel, fully human antibody directed against the human IL-11 receptor that is being developed to address the fibro-inflammatory pathology of pulmonary fibrosis and TED. 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 and tolerability of LASN01, and the secondary objective is to evaluate the preliminary efficacy, 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). Please note that both the Phase 1 (single and multiple ascending dose, SAD/MAD) portion in healthy volunteers and the Phase 2a portion in patients are completed.
Detailed description
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.
Interventions
DRUGLASN01
Escalating single and multiple doses of LASN01
DRUGPlacebo
Escalating doses of matching placebo
Sponsors
Lassen Therapeutics 1 PTY LTD
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
I. Participant Inclusion Criteria- Parts A, B, C, and D 1. 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. 2. 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 3. Males or females, 18 through 60 years of age, inclusive 4. Body weight ≥110 pounds (≥50 kg); body mass index (BMI) within the range of 18 through 32.0 kg/m2 5. In good health as determined by the Investigator Part C only 6. Male and female patients \>40 years of age (IPF patients) or ≥21 years of age (PF-ILD patients) IPF-specific Inclusion Criteria: 7. A diagnosis of IPF 8. IPF has been stable for ≥3 months at Screening PF-ILD-specific Inclusion Criteria: 9. 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. 10. Fibrosing lung disease on HRCT performed within 3 years of the Screening Visit 11. 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 12. FVC ≥45% predicted Part D only 13. Male or female patients of age ≥18 years 14. Clinical diagnosis of Graves' disease associated with active TED 15. Moderate-to-severe active TED 16. Less than 15 months from onset of TED in the study eye 17. 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 1. 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 2. Significant history or clinical manifestation of any significant endocrine, metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, or psychiatric disorder 3. History of significant hypersensitivity; intolerance; or allergy to any drug compound, food, or other substance; or history of anaphylaxis or angioedema 4. Positive serum test for HIV or hepatitis infection 5. Currently receiving any antibiotics for upper or lower respiratory tract infections 6. Use of any prescription drug or vaccine within 21 days before Check-in with the exception of hormonal contraceptives and vaccines. 7. Any prescription biologic within 3 months or 5 half-lives (whichever is greater) before Check-in 8. 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 9. History of clinically relevant cardiovascular disease that could jeopardize a patient's health during the course of the study 10. Patients with concurrent active malignancy other than adequately treated basal cell carcinoma of the skin or carcinoma in situ of the cervix IPF-specific
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Treatment emergent, treatment related, and serious adverse events | Day 1-Day 57 in Part A, Day 1-Day 71 in Part B, Day 1-Day 211 in Part C, Day 1-Day 365 in Part D |
| Changes in concomitant medications | Day 1-Day 57 in Part A, Day 1-Day 71 in Part B, Day 1-Day 211 in Part C, Day 1-Day 365 in Part D |
| Changes from Baseline in clinical laboratory evaluations following study drug administration | Day 1-Day 57 in Part A, Day 1-Day 71 in Part B, Day 1-Day 211 in Part C, Day 1-Day 365 in Part D |
| Changes from Baseline in vital signs following study drug administration | Day 1-Day 57 in Part A, Day 1-Day 71 in Part B, Day 1-Day 211 in Part C, Day 1-Day 365 in Part D |
| Changes from Baseline in 12-lead electrocardiogram (ECG) parameters following study drug administration | Day 1-Day 57 in Part A, Day 1-Day 71 in Part B, Day 1-Day 211 in Part C, Day 1-Day 365 in Part D |
| Changes from Baseline in physical examination (PE) results following study drug administration | Day 1-Day 57 in Part A, Day 1-Day 71 in Part B, Day 1-Day 211 in Part C, Day 1-Day 365 in Part D |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of patients with a ≥2 mm reduction from Baseline in proptosis in the study eye, (LASN01 versus placebo) without deterioration [≥2 mm increase] of proptosis in the fellow eye at Week 29 | Week 1-Week 29 in Part D |
| PK parameter assessed by serum LASN01 concentration at specified timepoints for maximum plasma concentration (Cmax) | Day 1-Day 57 in Part A, Day 1-Day 71 in Part B, Day 1-Day 211 in Part C, Day 1- Day 365 in Part D |
| Mean change from baseline in proptosis of LASN01 patients versus placebo patients | Day 1- Day 365 in Part D |
| PK parameter assessed by serum LASN01 concentration at specified timepoints for time to peak concentration (T max) | Day 1-Day 57 in Part A, Day 1-Day 71 in Part B, Day 1-Day 211 in Part C, Day 1- Day 365 in Part D |
| PK parameter assessed by serum LASN01 concentration at specified timepoints for area under curve (AUC) | Day 1-Day 57 in Part A, Day 1-Day 71 in Part B, Day 1-Day 211 in Part C, Day 1- Day 365 in Part D |
| PK parameter assessed by serum LASN01 concentration at specified timepoints for clearance volume (CL) | Day 1-Day 57 in Part A, Day 1-Day 71 in Part B, Day 1-Day 211 in Part C, Day 1- Day 365 in Part D |
| PK parameter assessed by serum LASN01 concentration at specified timepoints for terminal phase volume (Vz) | Day 1-Day 57 in Part A, Day 1-Day 71 in Part B, Day 1-Day 211 in Part C, Day 1- Day 365 in Part D |
| PK parameter assessed by serum LASN01 concentration at specified timepoints for half life ( t1/2). | Day 1-Day 57 in Part A, Day 1-Day 71 in Part B, Day 1-Day 211 in Part C, Day 1- Day 365 in Part D |
Countries
Australia, Hong Kong
Outcome results
None listed