Efgartigimod for Thyroid Eye Disease

(UplighTED Trial)

Recruiting at 95 trial locations

Overseen By Sabine s Coppieters, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: argenx

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

123 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called efgartigimod for individuals with thyroid eye disease (TED), a condition that can cause bulging eyes and vision problems due to autoimmune issues like Graves' disease or Hashimoto's thyroiditis. The study aims to evaluate the treatment's effectiveness and safety compared to a placebo. Participants will receive either the treatment or a placebo injection. Candidates may be suitable if they have experienced active thyroid eye disease symptoms for less than a year and have stable thyroid function. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a treatment that could soon become widely available.

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.

Is there any evidence suggesting that efgartigimod PH20 SC is likely to be safe for humans?

Research has shown that efgartigimod, the treatment under study for Thyroid Eye Disease (TED), underwent safety testing in earlier studies. Most participants tolerated efgartigimod well, with only mild to moderate side effects reported, while serious side effects were rare.

Efgartigimod has already received approval for other conditions, which supports its safety profile. However, since each condition differs, it is crucial to evaluate its effectiveness specifically for TED.

This study is at a stage where the treatment has already passed initial safety tests, providing researchers with some evidence of its safety in humans. Discuss any concerns with the trial team or your doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for TED?

Unlike the standard treatments for Thyroid Eye Disease, which often include steroids or surgery, Efgartigimod PH20 SC offers a novel approach by targeting the immune system more precisely. This treatment is an antibody fragment that reduces the levels of pathogenic antibodies, potentially addressing the root cause of the disease. Researchers are excited about Efgartigimod because it is administered via a subcutaneous injection, which can be easier and more convenient for patients compared to intravenous infusions. This innovative mechanism and delivery method could lead to more effective management of the disease with fewer side effects.

What evidence suggests that efgartigimod PH20 SC might be an effective treatment for thyroid eye disease?

This trial will compare Efgartigimod PH20 SC with a placebo for treating Thyroid Eye Disease (TED). Research has shown that Efgartigimod PH20 SC might help treat TED by calming the immune system to reduce inflammation and swelling. People with similar immune-related conditions have improved with efgartigimod, suggesting it could also ease TED symptoms. Studies have found that this medication is generally safe and well-tolerated. Although the full effects on TED are still under investigation, early results appear promising. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

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

My eye disease symptoms started less than a year ago.

I have been diagnosed with severe thyroid eye disease by a doctor.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Efgartigimod PH20 SC

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.

How Is the Trial Designed?

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 European Union, United States, Japan, China for the following indications:

Approved in European Union as VYVGART for:

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

Approved in United States as VYVGART Hytrulo for:

• Generalized myasthenia gravis in adults who are anti-acetylcholine receptor antibody positive
• Chronic inflammatory demyelinating polyneuropathy (CIDP)

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

Published Research Related to This Trial

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06307613

NCT06307613 | A Study of Efgartigimod PH20 SC Given ... This study aims to evaluate the efficacy, safety and tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of efgartigimod PH20 SC

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06307626

NCT06307626 | A Study of Efgartigimod PH20 SC Given ... This study aims to evaluate the efficacy, safety and tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of efgartigimod PH20 SC

3. argenx.com argenx.com/patients/clinical-trials

Clinical Trials UPLIGHTED. Phase 3 Study to Evaluate the Safety and Efficacy of Self-administered efgartigimod SC injection for Adults with Thyroid Eye Disease (TED).

4. dukehealth.org dukehealth.org/clinical-trials/directory/pro00118108

ARGX-113-2301 (UplighTED) - Clinical Trial This study is trying to find out if a new medicine called efgartigimod can help people who have Thyroid Eye Disease, or TED. The study also wants to make sure ...

5. clinicaltrials.eu clinicaltrials.eu/trial/study-of-efgartigimod-ph20-sc-for-adults-with-thyroid-eye-disease/

Study of Efgartigimod PH20 SC for Adults with Thyroid Eye ... This study tests the efficacy of Efgartigimod PH20 SC, a protein-based treatment, in managing symptoms of Thyroid Eye Disease in adult patients.

6. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/584295

A Study of Efgartigimod PH20 SC Given by Prefilled ... This study aims to evaluate the efficacy, safety and tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of efgartigimod PH20 SC