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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 75
- 试验地点
- 4
- 主要终点
- Changes from Baseline in 12-lead electrocardiogram (ECG) parameters following study drug administration
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
LASN01 - Parts A and B [Healthy Volunteers]
干预措施: LASN01 (Drug)
Placebo - Parts A and B [Healthy Volunteers]
干预措施: Placebo (Drug)
LASN01 - Part C [Pulmonary Fibrosis]
干预措施: LASN01 (Drug)
Placebo - Part C [Pulmonary Fibrosis]
干预措施: Placebo (Drug)
LASN01 - Part D [Thyroid Eye Disease]
干预措施: LASN01 (Drug)
Placebo - Part D [Thyroid Eye Disease]
干预措施: Placebo (Drug)
结局指标
主要结局
Changes from Baseline in 12-lead electrocardiogram (ECG) parameters following study drug administration
时间窗: 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
Treatment emergent, treatment related, and serious adverse events
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
次要结局
- 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 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)
- 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)
- 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)
- Mean change from baseline in proptosis of LASN01 patients versus placebo patients(Day 1- Day 365 in Part D)