Efgartigimod for Thyroid Eye Disease

(UplighTED Trial)

Recruiting in Palo Alto (17 mi)

+44 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, Cancer, 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/NCT06307613)

Do I have to stop taking my current medications for the trial?

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 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 involved in the disease process. ^{1 2 3 4 5}

Eligibility Criteria

Adults with active, moderate-to-severe thyroid eye disease (TED) who've had symptoms start within the last year can join. They must be over 18, able to consent and follow the study plan, have their thyroid condition under control or only mildly off balance. Participants need to use birth control and women must test negative for pregnancy.

Inclusion Criteria

I can sign the consent form and follow the study rules.

Participant agrees to use birth control consistent with local regulations and individuals 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.

Exclusion Criteria

Pregnant or lactating state or intention to become pregnant during the study

I had cancer but have been free of it for over 3 years or had certain cancers treated adequately.

I have taken specific medications as listed in the trial protocol.

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

Regular visits as per study protocol

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

Varies

Treatment Details

Interventions

• Efgartigimod PH20 SC (Monoclonal Antibodies)

Trial Overview The trial is testing Efgartigimod PH20 SC against a placebo in people with TED. It's a randomized study where two-thirds get the real drug and one-third gets a fake drug (placebo), given by injection for 24 weeks. Responders are observed for another year without treatment; nonresponders get more of the real drug.

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 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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Advanced Research Boynton Beach, FL

Martel Eye Medical Group Rancho Cordova, CA

Butchertown Clinical Trials Louisville, KY

North Valley Eye Medical Group, Inc. Mission Hills, CA

More Trial Locations

Who Is Running the Clinical Trial?

argenx Lead Sponsor

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] We have studied the role of eye muscle and thyroid autoimmunity in patients with Graves' hyperthyroidism with or without ophthalmopathy in an area of relatively low iodine intake. Antibody dependent cell mediated cytotoxicity (ADCC) and complement mediated antibody dependent cytotoxicity (CMAC) against thyroid and eye muscle cells, and levels of antibodies against TSH receptor antigen and the thyroid microsomal antigen (thyroid peroxidase) were determined in three groups of patients: (1) thyrotoxic with exophthalmos (TX, n = 28), (2) thyrotoxic without ophthalmopathy (GR, n = 10), and (3) euthyroid ophthalmopathy (EU, n = 12). The thyroid glandular mass of the EU group was significantly less (P less than 0.01) compared with TX or GR. Mean (+/- SD) TSH receptor antibody (TRAb) level was 27 +/- 14% in EU which was significantly lower compared with TX (52.4 +/- 20%) and GR (59 +/- 18%). The prevalence of microsomal antibodies were similar and not significantly different in the three groups. On the other hand the prevalence of positive ADCC and CMAC tests was significantly greater, and at higher levels, in EU (ADCC THY CELLS 10.9 +/- 8.9% SL, ADCC Eye muscle = 25.9 +/- 20% SL, CMAC = 70.2 +/- 43% SL) and TX (ADCC THY CELLS = 9.3 +/- 9.2% SL, ADCC Eye muscle = 20.1 +/- 19% SL, CMAC = 62.4 +/- 30% SL) compared to GR (ADCC THY CELLS = 4.4 +/- 9.5% SL, ADCC Eye muscle = 7.7 +/- 6.7% SL, CMAC = 24.7 +/- 23% SL).(ABSTRACT TRUNCATED AT 250 WORDS)

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

Presence of thyroid-associated ophthalmopathy in Hashimoto's thyroiditis. [2021] To determine the prevalence of ophthalmopathy in Hashimoto's patients and to make a comparison in subgroups of patients.

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

Efficacy of teprotumumab therapy in patients with long-duration thyroid eye disease. [2023] Teprotumumab, an inhibitor of the insulin-like growth factor 1 receptor (IGF-1R), was approved by the US Food and Drug Administration in January 2020 for the treatment of thyroid eye disease (TED). The clinical trials leading to its approval enrolled patients with recent disease onset and significant inflammatory symptoms and signs. Subsequent real-world teprotumumab use in patients with longer duration of disease also may be effective, and there have been several publications reporting on experience in these patient groups.

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

Increased frequency of euthyroid ophthalmopathy in patients with Graves' disease associated with myasthenia gravis. [2019] We previously showed that myasthenia gravis (MG) has a mild clinical expression when associated with autoimmune thyroid diseases (AITD). In the present study we have investigated the frequency of thyroid-associated ophthalmopathy (TAO) in patients with Graves' disease (GD) associated with MG as compared with GD patients without MG. A total of 418 patients with GD were studied, 31 with MG and 387 without MG. TAO was evaluated by physical examination, exophthalmometry, computerized tomography, and computerized visual fields assessment. The overall prevalence of TAO was similar in GD patients with MG (61.2%) and in those without MG (56.4%). When the analysis was restricted to GD patients with ocular MG, a greater frequency of TAO was found (84.6%), compared with GD patients without MG or with GD patients with generalized MG, although the differences did not reach the statistical significance. GD patients with MG had a significantly greater prevalence (12.9%) of euthyroid ophthalmopathy (clinically overt ophthalmopathy without previous and/or current hyperthyroidism) than those without MG (3.1%; p = 0.003). The results suggest a preferential association between the ocular manifestations of GD and MG, which may be due to immunological cross-reactivity against common autoimmune targets in the eye muscle as well as to a common genetic background.

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] To investigate the effect of pentoxifylline (PTX) in subjects with inactive Graves' ophthalmopathy (GO) through a specific quality of life (QOL) questionnaire and exophthalmometry readings.