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

A Phase 1/2, Adaptive, Multiple Dose Ranging Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Clinical Efficacy of Lonigutamab in Subjects With Thyroid Eye Disease (TED)

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

Study Overview

• Status: Completed
• Conditions: Thyroid Eye Disease
• Intervention / Treatment: Drug: Placebo; Drug: lonigutamab

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2109
      • Clinical Research Site
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Clinical Research Site
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Clinical Research Site
  • Victoria
    • East Melbourne, Victoria, Australia, 3002
      • Clinical Research Site
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Clinical Research Site
• United States
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Clinical Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Clinical Research Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48108
      • Clinical Research Site
  • New York
    • East Setauket, New York, United States, 11733
      • Clinical Research Site
    • New York City, New York, United States, 10028
      • Clinical Research Site
  • West Virginia
    • Morgantown, West Virginia, United States, 26505
      • Clinical Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• 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

Key Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Single SC injection of dose 1 of lonigutamab or placebo at Day 1 and Day 21	Drug: Placebo; subcutaneous injection; Drug: lonigutamab; subcutaneous injection
Experimental: Cohort 2; multiple doses of dose 2 of lonigutamab administered SC injection weekly	Drug: lonigutamab; subcutaneous injection
Experimental: Cohort 3; multiple doses of lonigutamab dose 3 administered SC injection every 4 weeks.	Drug: lonigutamab; subcutaneous injection
Experimental: Cohort 4; multiple doses of lonigutamab dose 4 administered SC injection every 4 or 3 weeks.	Drug: lonigutamab; subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK profile of lonigutamab	minimum observed concentration (Cmin)	Day 1 to Day 169
PK profile of lonigutamab	Maximum observed concentration (Cmax)	Day 1 to Day 169

Collaborators and Investigators

• Sponsor: ACELYRIN Inc.
• Investigators: Study Director: Keenan, MD, ValenzaBio, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2023
• Primary Completion (Actual): May 26, 2025
• Study Completion (Actual): May 26, 2025

Study Registration Dates

• First Submitted: December 20, 2022
• First Submitted That Met QC Criteria: January 12, 2023
• First Posted (Actual): January 13, 2023

Study Record Updates

• Last Update Posted (Estimated): July 1, 2025
• Last Update Submitted That Met QC Criteria: June 27, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: TED
• Additional Relevant MeSH Terms: Endocrine System Diseases; Genetic Diseases, Inborn; Autoimmune Diseases; Immune System Diseases; Eye Diseases, Hereditary; Graves Disease; Exophthalmos; Orbital Diseases; Goiter; Hyperthyroidism; Thyroid Diseases; Eye Diseases; Graves Ophthalmopathy
• Other Study ID Numbers: 421-01-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No