Efgartigimod for Thyroid Eye Disease

(UplighTED Trial)

Recruiting in Palo Alto (17 mi)

+51 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: argenx

Disqualifiers: Optic neuropathy, Corneal decompensation, Autoimmune disease, others

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

This study aims to evaluate the efficacy, safety and tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of efgartigimod PH20 SC in participants with active, moderate-to-severe TED, compared with placebo PH20 SC. After the screening period, eligible participants will be randomized in a 2:1 ratio to receive efgartigimod PH20 SC or placebo PH20 SC, respectively during the double-blinded treatment period (DBTP). At the end of the DBTP, participants may enter a follow-up observational period while off study drug. Some participants may also enter the open-label treatment period with efgartigimod PH20 SC. The study duration varies from approximately 60 to 110 weeks. An alternative list of clinical sites open for recruitment could be found in the other UplighTED study record (https://www.clinicaltrials.gov/study/NCT06307626)

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications, but it mentions that the use of some medications before screening is an exclusion criterion. It's best to discuss your current medications with the trial team to see if they might affect your eligibility.

How does the drug Efgartigimod PH20 SC differ from other treatments for thyroid eye disease?

Efgartigimod PH20 SC is unique because it targets the immune system by reducing the levels of specific antibodies that contribute to thyroid eye disease, offering a novel approach compared to existing treatments like teprotumumab, which targets a different receptor. Additionally, Efgartigimod PH20 SC is administered subcutaneously (under the skin), which may offer a more convenient option compared to intravenous treatments. ^{1 2 3 4 5}

Research Team

Eligibility Criteria

Adults with active, moderate-to-severe thyroid eye disease (TED) linked to autoimmune thyroid conditions like Graves' disease or Hashimoto's thyroiditis. Participants must have had TED symptoms start within the last year and be able to follow study procedures. They should have normal or near-normal thyroid function that is stable or being treated.

Inclusion Criteria

Participant agrees to use birth control consistent with local regulations and people of child-bearing potential must have a negative blood pregnancy test at screening and a negative urine pregnancy test before receiving the study drug

I am 18 years old or older.

My eye disease symptoms started less than a year ago.

Exclusion Criteria

Clinically significant active infection that is not sufficiently resolved in the investigator's opinion or positive serum test at screening for active infection with Hepatitis B virus (HBV), Hepatitis C virus (HCV), HIV

My cornea condition hasn't improved with medication.

I have had eye surgery or radiation for thyroid eye disease.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-Blinded Treatment Period

Participants receive efgartigimod PH20 SC or placebo PH20 SC in a double-blinded manner

24 weeks

Follow-up Observational Period

Participants are monitored for safety and effectiveness after treatment while off study drug

4-8 weeks

Open-label Treatment Period

Participants may opt into continuation of treatment with efgartigimod PH20 SC

Long-term

Treatment Details

Interventions

• Efgartigimod PH20 SC (Monoclonal Antibodies)

Trial Overview The trial tests Efgartigimod PH20 SC, a new medication for TED, against a placebo. Patients are randomly assigned in a 2:1 ratio to receive either the drug or placebo via injection over a 24-week period, followed by an observational phase to monitor long-term effects.

Participant Groups

Group I: Efgartigimod arm Experimental Treatment 1 Intervention

Participants with active, moderate-to-severe TED receiving Efgartigimod PH20 SC (subcutaneously) via pre-filled syringe (PFS)

Group II: Placebo arm Placebo Group 1 Intervention

Participants with active, moderate-to-severe TED receiving Placebo PH20 SC (subcutaneously) via pre-filled syringe (PFS)

Efgartigimod PH20 SC is already approved in Japan, China for the following indications:

Approved in Japan as VYVDURA for:

• Generalized myasthenia gravis in adults who are anti-acetylcholine receptor antibody positive

Approved in China as Efgartigimod alfa injection (subcutaneous injection) for:

• Generalized myasthenia gravis in adults who are anti-acetylcholine receptor antibody positive

Who Is Running the Clinical Trial?

argenx

Lead Sponsor

Trials

76

Recruited

11,500+

Tim Van Hauwermeiren

argenx

Chief Executive Officer since 2008

B.Sc. and M.Sc. in Bioengineering from Ghent University, Executive MBA from The Vlerick School of Management

Dr. Peter Ulrichts

argenx

Chief Medical Officer since 2023

MD from Maastricht University, PhD in Molecular Immunology from Maastricht University

Findings from Research

In patients with Graves' hyperthyroidism, those with exophthalmos (eye bulging) showed significantly higher levels of TSH receptor antibodies compared to those without ophthalmopathy, indicating a stronger autoimmune response in the presence of eye symptoms.

The study found that antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-mediated cytotoxicity (CMAC) were significantly higher in patients with euthyroid ophthalmopathy and thyrotoxic patients, suggesting that these immune mechanisms may play a role in the development of eye muscle involvement in Graves' disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunologically mediated cytotoxicity against human eye muscle and thyroid cells in euthyroid and thyrotoxic Graves' ophthalmopathy. Medeiros-Neto, G., Zhang, ZG., Lima, N., et al.[2019]

In a study of 110 patients with Hashimoto's thyroiditis, 22.7% exhibited eye changes, significantly higher than the 4% prevalence in control subjects, indicating a notable association between Hashimoto's and ophthalmopathy.

The most common eye symptom among Hashimoto's patients was upper eyelid retraction (11.8%), suggesting that routine ophthalmic examinations should be conducted for these patients to identify potential eye-related complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Presence of thyroid-associated ophthalmopathy in Hashimoto's thyroiditis. Kan, E., Kan, EK., Ecemis, G., et al.[2021]

Teprotumumab, an IGF-1R inhibitor approved for thyroid eye disease (TED), has shown effectiveness in improving symptoms like proptosis and diplopia even in patients with long-standing disease or those who have not responded to previous treatments.

Recent reports suggest that teprotumumab can benefit patients regardless of disease duration or inflammation markers, indicating its potential as a versatile treatment option for TED.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of teprotumumab therapy in patients with long-duration thyroid eye disease. Subramanian, PS., Cho, RI., Kahana, A.[2023]

In a study of 418 patients with Graves' disease, those with myasthenia gravis (MG) showed a similar overall prevalence of thyroid-associated ophthalmopathy (TAO) compared to those without MG (61.2% vs. 56.4%).

However, patients with ocular MG had a significantly higher prevalence of euthyroid ophthalmopathy (12.9%) compared to those without MG (3.1%), suggesting a potential immunological link between the two conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased frequency of euthyroid ophthalmopathy in patients with Graves' disease associated with myasthenia gravis. Marinò, M., Barbesino, G., Pinchera, A., et al.[2019]

Pentoxifylline (PTX) significantly improved quality of life scores in patients with inactive Graves' ophthalmopathy (GO) after 6 months of treatment, indicating its potential efficacy in managing symptoms associated with this condition.

Proptosis measurements also showed significant improvement in patients treated with PTX, with reductions in eye protrusion observed after 3 and 6 months, supporting the conclusion that PTX may be an effective treatment option for inactive GO.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pentoxifylline (PTX)--an alternative treatment in Graves' ophthalmopathy (inactive phase): assessment by a disease specific quality of life questionnaire and by exophthalmometry in a prospective randomized trial. Finamor, FE., Martins, JR., Nakanami, D., et al.[2017]

References

1. England pubmed.ncbi.nlm.nih.gov

Immunologically mediated cytotoxicity against human eye muscle and thyroid cells in euthyroid and thyrotoxic Graves' ophthalmopathy. [2019]

2. China pubmed.ncbi.nlm.nih.gov

Presence of thyroid-associated ophthalmopathy in Hashimoto's thyroiditis. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Efficacy of teprotumumab therapy in patients with long-duration thyroid eye disease. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Increased frequency of euthyroid ophthalmopathy in patients with Graves' disease associated with myasthenia gravis. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Pentoxifylline (PTX)--an alternative treatment in Graves' ophthalmopathy (inactive phase): assessment by a disease specific quality of life questionnaire and by exophthalmometry in a prospective randomized trial. [2017]