A Study of GenSci098 in Subjects With Active Thyroid Eye Disease

NCT06569758 | Recruiting Phase 1 FDA Drug

• 1 other identifier: GenSci098-101
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the safety and tolerability of single and multiple ascending subcutaneous doses of GenSci098 in patients with thyroid eye disease (TED)

Conditions

Safety; Tolerability; GenSci098; Thyroid Eye Disease (TED)

Outcome Measures

Primary Outcomes (1)

• Incidence and severity of adverse events (AEs) (physical examination, vital signs, laboratory tests, 12-lead electrocardiogram [ECG]).

  SAD Part: 169 days, MAD Part: 281 days

Secondary Outcomes (8)

• PK parameters after single and multiple subcutaneous doses of GenSci098: maximum concentration at steady state (Cmax,ss);

  SAD Part: 169 days, MAD Part: 281 days

• PK parameters after single and multiple subcutaneous doses of GenSci098: minimum concentration at steady state (Cmin,ss);

  SAD Part: 169 days, MAD Part: 281 days

• PK parameters after single and multiple subcutaneous doses of GenSci098: time to maximum concentration at steady state (Tmax,ss);

  SAD Part: 169 days, MAD Part: 281 days

• PK parameters after single and multiple subcutaneous doses of GenSci098: average concentration at steady state (Cav,ss);

  SAD Part: 169 days, MAD Part: 281 days

• PK parameters after single and multiple subcutaneous doses of GenSci098: area under the concentration-time curve at steady state (AUC0-τ,ss);

  SAD Part: 169 days, MAD Part: 281 days

Other Outcomes (27)

• Changes from baseline in serum inflammatory cytokines including interleukin (IL)-6

  SAD Part: 169 days, MAD Part: 281 days

• Changes from baseline in serum inflammatory cytokines including interleukin IL-8,

  SAD Part: 169 days, MAD Part: 281 days

• Changes from baseline in serum inflammatory cytokines including monocyte chemotactic protein 1 (MCP-1)

  SAD Part: 169 days, MAD Part: 281 days

Study Arms (2)

GenSci098

EXPERIMENTAL

Drug: GenSci098

GenSci098 Placebo

PLACEBO COMPARATOR

Drug: GenSci098 Placebo

Interventions

GenSci098 DRUG

subcutaneous , 5 dose levels(15mg, 45mg, 90mg, 180mg and 270mg) will be assigned.

GenSci098

GenSci098 Placebo DRUG

In SAD part only one dose of GenSci098 and GenSci098 Placebo to be given, in MAD part, multiple doses of GenSci098 and GenSci098 Placebo will be given.

GenSci098 Placebo

Eligibility Criteria

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

You may qualify if:

• At the time of signing the informed consent form (ICF): aged between 18 and 75 years (inclusive).
• Diagnosed by the physician as having active TED associated with Graves' disease (GD), based on clinical and laboratory test results, with a CAS ≥ 3 (on the 7-point scale) for the most severely affected eye at screening and baseline.
• Onset of active symptoms and signs of TED (including one or more of the following: redness of conjunctiva, swelling of conjunctiva (chemosis), redness of eyelids, swelling of eyelids, swelling of caruncle or plica, spontaneous retrobulbar pain, and pain on attempted upward or downward gaze) within 12 months prior to the screening visit.
• Positive for thyroid stimulating hormone receptor antibodies (TRAb) at screening.
• Moderate to severe TED (impacting the quality of life, requiring intervention but not threatening vision), usually with at least 2 of the following manifestations: (1) eyelid retraction width ≥ 2 mm, (2) moderate or severe soft tissue involvement, (3) proptosis ≥ 3 mm above normal for race and gender, (4) inconstant or constant diplopia.
• Participants must be euthyroid with the underlying disease under control, or have mild hypo- or hyperthyroidism at screening. (Only applicable to Part 1)
• Participants must have normal thyroid function or hyperthyroidism due to GD at screening. (Only applicable to Part 2)
• No prior treatment with antithyroid medications and/or thyroid hormone replacement therapy, or having taken antithyroid medications and/or thyroid hormone replacement therapy on a stable dose, or having not been treated with antithyroid medications and/or thyroid hormone replacement therapy due to intolerable side effects.
• Anyone who will not be required to need or receive any immediate or planned surgical ophthalmological intervention, corrective surgery or orbital irradiation during the study.
• Female participants must meet one of the following conditions to be eligible for the study:
• Infertile, defined as surgical sterilization (hysterectomy, bilateral salpingectomy, bilateral tubal ligation, or bilateral oophorectomy) at least 6 weeks prior to administration or menopausal (spontaneous amenorrhea ≥ 12 months which is not caused by underlying diseases and confirmed by serum follicle stimulating hormone \[FSH\] level ≥ 40 mIU/mL).
• Fertile female participants agree, from the start of the screening visit until 300 day after the last dose, to consistently and correctly use one of the following acceptable methods of effective contraception:
• Complete abstinence (based on the participant's preference and usual lifestyle).
• Use of oral contraceptives (estrogen and progesterone), and being on a stable dose of the same contraceptive medication for at least 3 months prior to study treatment.
• Injectable or implantable hormonal contraception, or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception with similar efficacy (failure rate \< 1%), such as a hormonal vaginal ring or transdermal hormonal contraception. 4) Vasectomized partner, with the procedure performed at least 6 months ago.

You may not qualify if:

• Decreased best corrected visual acuity due to optic neuropathy as defined by a decrease in vision of 2 or more lines on the Snellen chart or standard logarithmic chart, new visual field defect, or color defect secondary to optic nerve involvement within the last 6 months.
• Corneal injury not relieved by medical management.
• Improvement in CAS of ≥ 2 points within 1 month prior to screening or between screening and baseline.
• Decrease in proptosis of ≥ 2 mm within 1 month prior to screening or between screening and baseline.
• Previous orbital irradiation or surgery for TED.
• Use of any steroid (either intravenous or oral) with a cumulative dose equivalent to ≥ 1 g of methylprednisolone for TED within 4 weeks prior to screening (discontinued steroid eye drops arepermitted).
• Use of steroids for conditions other than TED within 4 weeks prior to screening (topical steroids for dermatological conditions and inhaled steroids are permitted).
• Drug therapy with biologics or peptides, including teprotumumab, rituximab, or tocilizumab, within 6 months or 5 half-lives of the drug (whichever is longer) prior to screening.
• Use of any non-steroidal immunosuppressive agents within the 3 months prior to screening.
• Pre-existing ophthalmic disease or autoimmune disease (other than TED) that, in the judgment of the investigator, would preclude study participation or complicate interpretation of study results.
• History of hyperthyroidism not caused by GD (e.g., toxic adenoma or toxic multinodular goiter), and/or current or previous history of thyroid storm. (Only applicable to Part 2)
• History of radioiodine treatment or thyroidectomy within 6 months prior to first dose. (Only applicable to Part 2)
• Individuals who cannot abstain from smoking/tobacco products from the screening period to the end of the study.
• Any known allergy to the components of the investigational product or analogues or previous allergic reactions to monoclonal antibodies.
• Known history /diagnosis of malignancy.

Sponsors & Collaborators

• Changchun GeneScience Pharmaceutical Co., Ltd.: lead

Study Sites (1)

Shanghai Ninth People's hospital, Shanghai Jiaotong University School of Medication

Shanghai, Shanghai Municipality, 200011, China

RECRUITING

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 Officials

• Huifang Zhou, PHD

  Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jun Yan

CONTACT

+8615800359085; yanjun01@genscigroup.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2024
• First Posted: August 26, 2024
• Study Start: September 24, 2024
• Primary Completion (Estimated): September 2, 2027
• Study Completion (Estimated): December 13, 2027
• Last Updated: February 11, 2026

Record last verified: 2026-02

Locations

CN (1)