Efficacy and Safety of Lonigutamab in Subjects With Thyroid Eye Disease (TED)

NCT05683496 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 421-01-02
• Study Type: interventional
• Target: 31
• Locations: 2 countries
• Sites: 11

Brief Summary

Phase 1/2, multicenter, multiple dose clinical study designed to evaluate lonigutamab in subjects with TED.

Conditions

Thyroid Eye Disease

Keywords

TED

Outcome Measures

Primary Outcomes (2)

• Incidence and characterization of nonserious treatment emergent adverse events (TEAEs)

  Safety and Tolerability

  Day 1 to Day 169

• Incidence and characterization of serious treatment emergent adverse events (TEAEs)

  Safety and Tolerability

  Day 1 to Day 169

Secondary Outcomes (2)

• PK profile of lonigutamab

  Day 1 to Day 169

• PK profile of lonigutamab

  Day 1 to Day 169

Study Arms (4)

Cohort 1

EXPERIMENTAL

Single SC injection of dose 1 of lonigutamab or placebo at Day 1 and Day 21

Drug: lonigutamab; Drug: Placebo

Cohort 2

EXPERIMENTAL

multiple doses of dose 2 of lonigutamab administered SC injection weekly

Drug: lonigutamab

Cohort 3

EXPERIMENTAL

multiple doses of lonigutamab dose 3 administered SC injection every 4 weeks.

Drug: lonigutamab

Cohort 4

EXPERIMENTAL

multiple doses of lonigutamab dose 4 administered SC injection every 4 or 3 weeks.

Drug: lonigutamab

Interventions

lonigutamab DRUG

subcutaneous injection

Cohort 1; Cohort 2; Cohort 3; Cohort 4

Placebo DRUG

subcutaneous injection

Cohort 1

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, ≥18 and ≤75 years of age.
• Proptosis defined in the study eye as ≥3 mm above normal.
• Clinical Activity Score (CAS) ≥4 (using a 7-item scale) for the most severely affected eye
• Onset of active TED symptoms prior to baseline
• Must agree to use highly effective contraception as specified in the protocol

You may not qualify if:

• Pathology related to inflammatory bowel disease or irritable bowel syndrome.
• Clinically significant pathology related to hearing or history of hearing impairment
• Optic neuropathy
• Corneal decompensation unresponsive to medical management.
• Previous orbital irradiation (for any cause) or any previous surgical treatment for TED.
• Subjects with diabetes or hemoglobin A1c \>6.0% at screening
• Any steroid use (intravenous \[IV\] or oral) with a cumulative dose equivalent to \>3 g of methylprednisolone for the treatment of TED within the last year.
• Previous steroid use (IV or oral) specifically for the treatment of TED not to exceed 1 g total dose in the 8 weeks prior to Screening.
• Previous use of teprotumumab or any other IGF-1 receptor (IGF-1R) inhibitor.
• Any previous treatment with a biologic drug for the treatment of TED (eg, rituximab and tocilizumab)
• Any other immunosuppressive agent within 1 month of screening.
• Cohort 4 only: Prior history of craniofacial surgery or medical conditions that could alter orbital or facial features.

Sponsors & Collaborators

• ACELYRIN Inc.: lead

Study Sites (11)

Clinical Research Site

Jacksonville, Florida, 32216, United States

Location

Clinical Research Site

Atlanta, Georgia, 30328, United States

Location

Clinical Research Site

Ann Arbor, Michigan, 48108, United States

Location

Clinical Research Site

East Setauket, New York, 11733, United States

Location

Clinical Research Site

New York, New York, 10028, United States

Location

Clinical Research Site

Morgantown, West Virginia, 26505, United States

Location

Clinical Research Site

Sydney, New South Wales, 2109, Australia

Location

Clinical Research Site

Woolloongabba, Queensland, 4102, Australia

Location

Clinical Research Site

Adelaide, South Australia, 5000, Australia

Location

Clinical Research Site

East Melbourne, Victoria, 3002, Australia

Location

Clinical Research Site

Nedlands, Western Australia, 6009, Australia

Location

MeSH Terms

Conditions

Graves Ophthalmopathy

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Graves Disease; Exophthalmos; Orbital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Goiter; Thyroid Diseases; Endocrine System Diseases; Hyperthyroidism; Autoimmune Diseases; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-masked, placebo-controlled and open label
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Up to 4 cohorts are planned, with each cohort receiving one of 5 different treatment doses

Study Record Dates

• First Submitted: December 20, 2022
• First Posted: January 13, 2023
• Study Start: February 14, 2023
• Primary Completion: May 26, 2025
• Study Completion: May 26, 2025
• Last Updated: July 1, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (6); AU (5)