Thyroid Eye Disease, Graves Ophthalmopathy, Graves Orbitopathy, Thyroid Associated Ophthalmopathy, Endocrine System Diseases, Orbital Diseases, Proptosis, Eye Diseases
Conditions
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 treatment effect, safety, 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.
Interventions
DRUGLASN01
Low dose of LASN01 will be administered intravenously.
DRUGPlacebo
Placebo will be administered intravenously.
Sponsors
Lassen Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double masked treatment arms for patients without prior anti-IGF-1R treatment, and open-label treatment arm for patients with prior teprotumumab treatment
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Showing a Response in Proptosis Measured Using Hertel Exophthalmometer (≥2 mm Decrease From Baseline) in the Study Eye and Separately in Either Eye Without Increased Proptosis (≥2 mm Increase) in the Other Eye | Day 1-Day 253 | — |
| For Randomized Treatment Arms: Number of Participants With Adverse Events Receiving LASN01 Compared to Placebo | Day 1-Day 393 | Pooled analysis of 300 and 600 mg Q4W as compared with placebo. |
| For Open-label Treatment Arm: Number of Participants With Adverse Events Receiving LASN01 | Day 1-Day 393 | — |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Participants Showing a Response in Clinical Activity Score (CAS) in the Study Eye Compared to Baseline as Assessed by CAS Evaluation | Day 1-Day 253 |
Countries
Spain, United Kingdom, United States
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 48.0 years STANDARD_DEVIATION 16.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 1 Participants |
| Study Eye Iris Color Black | 3 Participants |
| Study Eye Iris Color Blue | 5 Participants |
| Study Eye Iris Color Brown | 24 Participants |
| Study Eye Iris Color Gray | 2 Participants |
| Study Eye Iris Color Green | 0 Participants |
| Study Eye Iris Color Hazel | 2 Participants |
| Study Eye Iris Color Other | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 8 | 0 / 9 | 0 / 15 |
| other Total, other adverse events | 4 / 9 | 6 / 8 | 6 / 9 | 7 / 15 |
| serious Total, serious adverse events | 0 / 9 | 0 / 8 | 0 / 9 | 1 / 15 |
Outcome results
None listed