Teprotumumab for Graves' Eye Disease

Recruiting at 46 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Amgen

Must not be taking: Steroids

Disqualifiers: Optic neuropathy, Corneal decompensation, others

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

The study consists of a randomized double-masked, placebo-controlled, parallel-group, multicenter trial with an optional open-label treatment period for proptosis non-responders who complete the Double-masked Treatment Period.

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.

What data supports the effectiveness of the drug Teprotumumab for Graves' Eye Disease?

Teprotumumab has been shown to be effective in treating thyroid eye disease (Graves' Eye Disease) based on positive results from two multinational clinical trials, leading to its approval in the US. It works by targeting a specific receptor involved in the disease, helping to reduce inflammation and symptoms. ^{1 2 3 4 5}

Is Teprotumumab safe for humans?

Teprotumumab, used for treating thyroid eye disease, has some common side effects like nausea, diarrhea, muscle spasms, and hearing issues. There was a case of a man experiencing cognitive decline, which improved after stopping the treatment, suggesting it might have been caused by the drug. More research is needed to fully understand its safety. ^{1 4 6 7 8}

How is the drug Teprotumumab different from other treatments for Graves' eye disease?

Teprotumumab is unique because it is a monoclonal antibody that specifically targets and blocks the insulin-like growth factor-I receptor, reducing inflammation and symptoms of thyroid eye disease. It is the first drug approved specifically for this condition, offering a novel approach compared to traditional treatments. ^{1 2 4 5 6}

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Teprotumumab (Monoclonal Antibodies)

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.

Participant Groups

Group I: Teprotumumab Experimental Treatment 1 Intervention

Teprotumumab administered SC

Group II: Placebo Placebo Group 1 Intervention

Placebo for teprotumumab administered SC

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+

Findings from Research

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 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]

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]

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]

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, 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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Teprotumumab (Tepezza): from the discovery and development of medicines to USFDA approval for active thyroid eye disease (TED) treatment. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Intraocular pressure improvement in patients receiving teprotumumab for the treatment of thyroid eye disease: a case series. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

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

4. New Zealand pubmed.ncbi.nlm.nih.gov

Teprotumumab: First Approval. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Teprotumumab for chronic thyroid eye disease. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Teprotumumab: a disease modifying treatment for graves' orbitopathy. [2023]

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

Teprotumumab-Related Adverse Events in Thyroid Eye Disease: A Multi-Center Study. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Rapidly progressive cognitive decline associated with teprotumumab in thyroid eye disease. [2021]