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

Pulmonary Fibrosis Clinical Trial

Official title:

A Phase 1/2a, Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose Study to Determine the Safety, Tolerability, Preliminary Efficacy, Immunogenicity and Pharmacokinetic Properties of LASN01 in Healthy Subjects and in Patients With Pulmonary Fibrosis or Thyroid Eye Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05331300
• Other study ID #: LASN01-CL-1101
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: June 6, 2022
• Est. completion date: September 2025

Study information

• Verified date: April 2024
• Source: Lassen Therapeutics Inc.
• Contact: Lassen Therapeutics
• Phone: +1 858 251-7528
• Email: CL-1101[@]lassentherapeutics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 the Phase 1 (single and multiple ascending dose, SAD/MAD) portion in healthy subjects is completed and the Phase 2a portion in patients is actively recruiting.

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 will comprise a multiple-dose administration in a single cohort of approximately 12 to 16 patients with IPF and PF-ILD, and Part D will comprise a multiple-dose design in a single cohort of approximately 12 to 16 patients with TED. In each part of the study, participants will be randomized to receive IV doses of LASN01 or placebo.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: September 2025
• Est. primary completion date: September 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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 Exclusion Criteria:

11. FVC <45% predicted of normal or a forced expiratory volume during the first second of the forced breath (FEV1)/FVC ratio of <0.7

12. Extent of emphysema in the lungs exceeds fibrosis

13. 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:

14. Diagnosis of IPF

15. Diagnosis of sarcoidosis

16. Significant pulmonary arterial hypertension

17. FVC <45% predicted of normal or a FEV1/FVC ratio of <0.7

18. Previous treatment with pirfenidone Part D only

19. Any previous use of anti-insulin-like growth factor 1 receptor monoclonal antibody (eg, teprotumumab) at any time

20. 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

21. 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

Related Conditions & MeSH terms

• Eye Diseases
• Fibrosis
• Graves Ophthalmopathy
• Pulmonary Fibrosis
• Thyroid Diseases
• Thyroid Eye Disease

Intervention

Drug:
• LASN01
Escalating single and multiple doses of LASN01
• LASN01
LASN01 will be administered intravenously
• Placebo
Escalating doses of matching placebo
• Placebo
Placebo will be administered intravenously

Locations

Country	Name	City	State
Australia	Site AU07	Botany	New South Wales
Australia	Site AU03	Brisbane	Queensland
Australia	Site AU06	Camberwell	Victoria
Australia	Site AU05	Hurstville	New South Wales
Australia	Site AU01	Melbourne	Victoria
Hong Kong	Site HK01	Sha Tin
New Zealand	Site NZ02	Auckland
New Zealand	Site NZ01	Wellington

Sponsors (1)

Lead Sponsor	Collaborator
Lassen Therapeutics 1 PTY LTD

Countries where clinical trial is conducted

Australia,  Hong Kong,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Mean change from baseline in proptosis of LASN01 patients versus placebo patients		Day 1- Day 365 in Part D