Teprotumumab for Graves' Eye Disease

Not currently recruiting at 71 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Amgen

Must not be taking: Steroids

Disqualifiers: Optic neuropathy, Corneal decompensation, 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 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called teprotumumab to determine its effectiveness for people with Graves’ eye disease, a condition that can cause bulging eyes, double vision, and other eye problems. Researchers aim to find out if teprotumumab can reduce symptoms like eye bulging and improve patients' daily lives. They will compare teprotumumab with a placebo (a substance with no active drug) to assess its effectiveness. Individuals who have experienced symptoms of moderate-to-severe Graves' eye disease for less than 15 months and find it impacts their daily life might be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires that you stop using systemic steroids (IV or oral) or steroid eye drops for TED or other conditions at least 3 weeks before screening. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

Is there any evidence suggesting that teprotumumab is likely to be safe for humans?

Research has shown that teprotumumab, approved by the FDA for treating Thyroid Eye Disease (TED), appears safe for people. Studies have found that teprotumumab can greatly improve eye problems like bulging and double vision. Although some serious side effects have been reported, many patients tolerate the treatment well. Notably, teprotumumab, a special type of antibody treatment, has undergone thorough testing in earlier research, which bolsters confidence in its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Graves' Eye Disease?

Teprotumumab is unique because it specifically targets and inhibits the insulin-like growth factor-1 receptor (IGF-1R), which is thought to play a key role in the development of Graves' eye disease. Unlike traditional treatments for this condition, such as corticosteroids or orbital radiotherapy, teprotumumab works at a molecular level to directly address the underlying cause of the inflammation and tissue expansion. Researchers are excited about this treatment because it has shown promising results in reducing eye bulging and improving quality of life for patients, marking a potential breakthrough in targeted therapy for Graves' eye disease.

What evidence suggests that teprotumumab might be an effective treatment for Graves' Eye Disease?

Research has shown that teprotumumab effectively treats Graves' Eye Disease, also known as Thyroid Eye Disease (TED). Studies have demonstrated that this treatment significantly improves symptoms such as bulging eyes, double vision, and overall eye health. In this trial, participants will receive either teprotumumab or a placebo. Teprotumumab, compared to a placebo, results in better eye comfort and quality of life. It blocks a specific protein that causes inflammation and swelling in TED. The FDA has already approved this treatment for the condition, providing strong evidence of its effectiveness. ^{1 2 3 5 6}

Who Is on the Research Team?

MD

Principal Investigator

Amgen

Are You a Good Fit for This Trial?

Adults aged 18-80 with moderate-to-severe active Thyroid Eye Disease (TED) linked to Graves' disease can join. They should have had TED symptoms start within the last 15 months, not need immediate eye surgery, and be able to follow trial procedures. Women must test negative for pregnancy.

Inclusion Criteria

Participant is willing and able to comply with the protocol requirements for the duration of the trial

I don't need eye surgery or treatment during the trial.

My eye bulges out more than it did before by at least 3 mm.

Exclusion Criteria

Participant has a decrease in CAS of ≥ 2 points between Screening and Baseline

I have had surgery or radiation treatment on my eye socket.

I plan to undergo eyelid surgery during the trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-masked Treatment

Participants receive either teprotumumab or placebo subcutaneously to evaluate efficacy, safety, and tolerability

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label Extension (optional)

Proptosis non-responders may opt into continuation of teprotumumab treatment

What Are the Treatments Tested in This Trial?

Interventions

• Teprotumumab

Trial Overview The trial is testing Teprotumumab against a placebo in adults with active TED. Participants are randomly assigned to receive either the drug or placebo, without knowing which one they get, in a controlled environment across multiple centers.

How Is the Trial Designed?

Group I: Teprotumumab Experimental Treatment 1 Intervention

Teprotumumab administered SC

Group II: Placebo Placebo Group 1 Intervention

Placebo for teprotumumab administered SC

Teprotumumab is already approved in United States for the following indications:

Approved in United States as Tepezza for:

• Thyroid Eye Disease

Who Is Running the Clinical Trial?

Amgen

Lead Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Horizon Pharma USA, Inc.

Lead Sponsor

Trials

23

Recruited

2,100+

Published Research Related to This Trial

Tepezza (teprotumumab) has been approved by the FDA for treating active Graves' orbitopathy, showing significant positive outcomes in two large clinical trials, particularly in reversing proptosis (eye bulging).

Teprotumumab may change the treatment approach for thyroid eye disease, providing a non-surgical alternative, but further studies are needed to confirm its long-term effects and identify the best patient candidates for this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teprotumumab: a disease modifying treatment for graves' orbitopathy. Ting, M., Ezra, DG.[2023]

In a study of 131 patients with thyroid eye disease treated with teprotumumab, 77% experienced significant improvement in proptosis, indicating the drug's efficacy in reducing eye bulging associated with the condition.

While 81.7% of patients reported adverse events, most were mild and reversible; however, serious adverse events occurred in some cases, leading to treatment discontinuation in 12.2% of patients, highlighting the need for careful monitoring and patient education regarding potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teprotumumab-Related Adverse Events in Thyroid Eye Disease: A Multi-Center Study. Shah, SA., Amarikwa, L., Sears, CM., et al.[2023]

Teprotumumab is a monoclonal antibody that acts as an antagonist to the insulin-like growth factor-I receptor (IGF-IR) and has been developed specifically for treating thyroid eye disease, also known as Graves ophthalmopathy.

The drug received approval in the US following positive outcomes from two multinational clinical trials, marking a significant milestone in its development for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teprotumumab: First Approval. Markham, A.[2020]

Teprotumumab is the first and only FDA-approved medical therapy for thyroid-associated ophthalmopathy (TAO), a serious autoimmune condition linked to Graves' disease that can cause significant facial disfigurement and vision loss.

The development of teprotumumab is based on the understanding that the insulin-like growth factor I receptor plays a crucial role in the disease's progression, suggesting potential for similar treatments in other autoimmune diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teprotumumab as a Novel Therapy for Thyroid-Associated Ophthalmopathy. Smith, TJ.[2021]

In a study of nine patients with chronic thyroid eye disease (TED) and low clinical activity scores, treatment with teprotumumab resulted in a significant average reduction of 4.0 mm in proptosis (eye bulging) immediately after treatment, indicating its efficacy.

Despite some reported side effects, such as myalgias and hair thinning, teprotumumab appears to be a promising treatment option for patients with chronic TED, as evidenced by sustained proptosis reduction observed in follow-up assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teprotumumab for chronic thyroid eye disease. Ozzello, DJ., Dallalzadeh, LO., Liu, CY.[2022]

Teprotumumab (Tepezza) is a monoclonal antibody that has been approved by the USFDA for treating thyroid eye disease (TAO), demonstrating its efficacy as a targeted therapy for this condition.

The drug has received multiple designations, including orphan drug status and breakthrough designation, highlighting its significance and potential in treating a rare disease with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teprotumumab (Tepezza): from the discovery and development of medicines to USFDA approval for active thyroid eye disease (TED) treatment. Ali, F., Chorsiya, A., Anjum, V., et al.[2021]

Teprotumumab, a novel treatment for thyroid eye disease, significantly reduced intraocular pressure in nine patients over an 8-week treatment period, indicating its potential benefits beyond just alleviating symptoms of the disease.

While teprotumumab is effective in lowering intraocular pressure, it should not replace glaucoma medications, as its mechanism may involve reducing both periorbital and retro-orbital pressure rather than directly treating glaucoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraocular pressure improvement in patients receiving teprotumumab for the treatment of thyroid eye disease: a case series. Chu, M., Sung, J., Song, M., et al.[2022]

Teprotumumab, an approved treatment for thyroid eye disease, can cause serious side effects, including a case of rapidly progressive cognitive decline in a 76-year-old patient after four doses.

The patient's symptoms improved after plasmapheresis, suggesting a possible link between teprotumumab and encephalopathy, highlighting the need for further research on its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapidly progressive cognitive decline associated with teprotumumab in thyroid eye disease. Hoang, TD., Nguyen, NT., Chou, E., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9312457/

Teprotumumab (Tepezza) for Thyroid Eye Disease - PMC Teprotumumab is currently the only Federal Drug Administration approved therapy for the treatment of TED. Significant improvements in proptosis, diplopia and ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1910434

Teprotumumab for the Treatment of Active Thyroid Eye ... Teprotumumab resulted in better outcomes with respect to proptosis, Clinical Activity Score, diplopia, and quality of life than placebo; serious adverse events ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03298867

NCT03298867 | Treatment of Graves' Orbitopathy (Thyroid ... The overall objective is to investigate the efficacy, tolerability, and safety of teprotumumab (a fully human monoclonal antibody [mAb] inhibitor of the ...

4. tepezzahcp.com tepezzahcp.com/about-tepezza/tepezza-efficacy

TEPEZZA® for HCPs - TEPEZZA® (teprotumumab-trbw) Efficacy Responses assessed included clinical activity score (CAS ≥2-point improvement), the European Group of Graves' Orbitopathy ophthalmic composite outcome, diplopia ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38824618/

Long-Term Efficacy of Teprotumumab in Thyroid Eye Disease Teprotumumab, an insulin-like growth factor-I receptor inhibitor, demonstrated improvements in TED signs and symptoms in three adequately powered clinical ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1530891X25000448

Efficacy and Safety of Teprotumumab in Thyroid Eye Disease Teprotumumab effectively reduces proptosis, improves diplopia, and lowers disease activity in TED, regardless of previous treatments, severity, or dosage.