Clinical trial NCT06226545: A Study to Evaluate the Efficacy and Safety of LASN01 in Patients With Thyroid Eye Disease
Official title: A Phase 2, Proof-of-Concept, Randomized, Double-Masked, Placebo-Controlled Study to Determine the Efficacy and Safety of LASN01 in Patients With Thyroid Eye Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Thyroid Eye Disease
Graves Ophthalmopathy
Graves Orbitopathy
Thyroid Associated Ophthalmopathy
Endocrine System Diseases
Orbital Diseases
Proptosis
Eye Diseases
Lead sponsor: Lassen Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2024-01-26
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: LASN01 is a novel, fully human antibody directed against the human IL-11 receptor being developed for treatment of patients with thyroid eye disease (TED).

The primary and secondary objectives of this study are to evaluate the safety, treatment effect, and pharmacokinetics of LASN01 administered IV in patients with TED with no prior anti-IGF-1R treatment or in patients with TED who have previously received teprotumumab treatment.

Detailed description: This clinical trial (LASN01-CL-2201) comprises a multiple-dose design in 3 parallel treatment arms for patients with TED with no prior anti-IGF-1R treatment, and a 4th treatment arm for patients with TED who have previously received teprotumumab treatment.

Eligibility criteria: Inclusion Criteria:

1. Male or female patients ≥18 years of age at the time of Screening
2. Clinical diagnosis of Graves' disease associated with active TED
3. Moderate-to-severe active TED
4. Female patients must be nonpregnant, nonlactating, surgically sterile for ≥6 months, or agree to use a highly effective method of contraception. Males must be surgically sterile or agree to use a highly effective method of contraception.
5. No previous:

   1. Medical treatment for TED, with the exception of:

      * Local supportive measures;
      * Mycophenolate, and oral or injectable steroids;
      * Immunomodulating therapies
      * For the open-label treatment arm only: Previous treatment with teprotumumab is required.
   2. Orbital surgery
   3. Orbital radiation
6. Patients

   * Without prior anti-IGF-1R treatment: less than 15 months from onset of TED symptoms
   * With prior teprotumumab treatment: depending on time of diagnosis or reactivation of disease

Exclusion Criteria:

1. Patients with 2 mm proptosis decrease between Screening and Day 1, or a 1-point decrease on the CAS 7-point scale between Screening and Day 1
2. Patients with a known decreased best corrected visual acuity due to optic neuropathy as defined by a decrease in vision of 3 lines on the Snellen chart, new visual field defect, or color defect secondary to optic nerve involvement within the last 6 months before Screening; or any known optic neuropathy or compression or any neurologic or neuro-ophthalmologic condition that may result in visual field loss.
3. Previous or any planned orbital irradiation/radiotherapy or orbital surgery for TED during the study period (ie, treatment and FU)
4. Use of oral and/or IV corticosteroid for conditions other than TED in the 6 weeks before Day 1 (topical steroids for conditions other than TED are allowed)
5. Active autoimmune disorder(s) requiring or likely to require treatment (other than Grave's disease and TED) that would interfere with study assessments, as determined by the PI or designee
6. Any previous use of anti-IGF-1R monoclonal antibody (eg, teprotumumab) at any time, with exception to the open-label post-teprotumumab treatment arm where prior use of teprotumumab is required
7. Use of selenium within 3 weeks before Day 1 or expected use during the clinical trial (multivitamins that include selenium are allowed in usual doses)
8. Use or expected use of biotin (including multivitamins that include biotin) within 2 days before any laboratory collection

Primary outcomes:
measure: Changes in proptosis in the study eye compared to baseline as assessed by Exophthalmometer
timeFrame: Day 1-Day 253
measure: For randomized treatment arms: Number of participants with adverse events receiving LASN01 compared to placebo
timeFrame: Day 1-Day 253
measure: For open-label treatment arm: Number of participants with adverse events receiving LASN01
timeFrame: Day 1-Day 253
Secondary outcomes:
measure: Change in Clinical Activity Score (CAS) in the study eye compared to baseline as assessed by CAS evaluation
timeFrame: Day 1-Day 505
measure: Change in lid aperture in the study eye compared to baseline as measured by the changes of the distance between the lid margins
timeFrame: Day 1-Day 505
measure: Change in lid retraction in the study eye compared to baseline as assessed by measurement of margin reflex distance 1 and 2
timeFrame: Day 1-Day 505
measure: Change in lagophthalmos in the study eye compared to baseline as assessed by presence or absence of lagophthalmos
timeFrame: Day 1-Day 505
measure: Change in Von Graefe's sign in the study eye compared to baseline as assessed by presence or absence of Von Graefe's sign
timeFrame: Day 1-Day 505
measure: Change in extraocular movements in the study eye compared to baseline as assessed by duction testing
timeFrame: Day 1-Day 505
measure: Change in diplopia in the study eye compared to baseline as assessed by Bahn-Gorman Scale
timeFrame: Day 1-Day 505
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Site 111
state: California
city: Palo Alto
country: United States
facility: Site 105
state: California
city: San Diego
country: United States
facility: Site 101
state: California
city: Miami
country: United States
facility: Site 103
state: Florida
city: Livonia
country: United States
facility: Site 108
state: Michigan
city: Las Vegas
country: United States
facility: Site 112
state: Nevada
city: Wilmington
country: United States
facility: Site 110
state: North Carolina
city: Houston
country: United States
facility: Site 106
state: Texas
city: Houston
country: United States
facility: Site 104
state: Texas
city: Seattle
country: United States
facility: Site 109
state: Washington
city: Córdoba
country: Spain
facility: Site 302
city: Sevilla
country: Spain
facility: Site 301
city: London
country: United Kingdom
facility: Site 201
city: London
country: United Kingdom
facility: Site 206
city: Newcastle Upon Tyne
country: United Kingdom
facility: Site 204
Study officials:
References: