AMG 732 for Thyroid Eye Disease

Recruiting at 16 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Amgen

Must not be taking: Steroids

Disqualifiers: Malignant condition, Active liver disease, Hepatitis, Diabetes, Substance abuse, others

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

88 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new treatment, AMG 732, for individuals with Thyroid Eye Disease (TED), which causes eye swelling and discomfort. The first part of the study examines the treatment's safety after one dose, while the second part assesses its effectiveness after several doses. Candidates for the second part include those with moderate to severe TED that began within the last 15 months, causing eye bulging and double vision. As a Phase 1 trial, this research aims to understand how AMG 732 works in people, offering participants the opportunity to be among the first to receive this new treatment.

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

The trial requires that you stop using any steroids (IV, oral, or steroid eye drops) at least 3 weeks before screening and during the trial. However, you can continue using topical and inhaled steroids, as well as steroids for injection site reactions. The protocol does not specify other medication restrictions, so it's best to discuss your current medications with the trial team.

Will I have to stop taking my current medications?

The trial requires that you stop using any steroids (like IV, oral, or steroid eye drops) at least 3 weeks before screening and during the trial, except for topical and inhaled steroids or those used for injection site reactions.

Is there any evidence suggesting that AMG 732 is likely to be safe for humans?

Research shows that AMG 732 remains in the early testing stages, so limited information exists about its safety in humans. However, studies have focused on its tolerability. These studies include both healthy participants and those with Thyroid Eye Disease (TED).

The main goal is to identify any side effects and understand how the body processes the drug. Detailed safety results are not yet available, as this is a Phase 1 study, which primarily ensures human safety. Researchers closely monitor participants for negative effects to confirm the drug's tolerability.

AMG 732 undergoes testing at different doses, with safety carefully monitored across all groups to assess how varying amounts affect safety. This process helps determine the safest dose for future studies. ^{1 2 3 4 5}

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

Most treatments for Thyroid Eye Disease (TED), like corticosteroids, aim to reduce inflammation. But AMG 732 works differently, potentially targeting the underlying causes of the disease more precisely. Researchers are excited because AMG 732 offers a novel approach, possibly providing more effective and sustained results compared to current therapies. Moreover, it could present fewer side effects and be administered in a way that's more convenient for patients.

What evidence suggests that AMG 732 could be an effective treatment for Thyroid Eye Disease?

Researchers are investigating AMG 732 as a potential treatment for Thyroid Eye Disease (TED), which causes swelling and inflammation in the eyes. In this trial, participants will receive either AMG 732 or a placebo in different dosing regimens to assess its effectiveness. Although limited information exists on AMG 732's efficacy in people, it is being developed to specifically target and reduce these symptoms. The drug aims to work by affecting certain processes that cause inflammation. Early studies in other diseases have shown positive results, suggesting it might also alleviate TED symptoms. Ongoing trials will provide more insight into its effectiveness. ^{1 2 5 6 7}

Who Is on the Research Team?

MD

Principal Investigator

Amgen

Are You a Good Fit for This Trial?

This trial is for healthy adults aged 18-55 with a BMI of 18-30, and women must be unable to bear children. Participants should have good health as confirmed by various medical assessments. It's also open to healthy Japanese individuals who meet specific heritage criteria but haven't lived outside Japan for more than 10 years.

Inclusion Criteria

I tested positive for hepatitis B or have been vaccinated against it.

My liver is not functioning properly, with high ALT or AST levels.

I have signed the consent form for this study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AMG 732 or placebo in Single Ascending Doses (SAD)

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AMG 732

Trial Overview The study is testing the safety and tolerability of a single subcutaneous dose of AMG 732 in people without any health issues and those with Thyroid Eye Disease, comparing it against a placebo.

How Is the Trial Designed?

Group I: Part B: AMG 732 Medium Dose Experimental Treatment 1 Intervention

Participants will receive AMG 732 medium dose SC.

Group II: Part B: AMG 732 Low Dose Experimental Treatment 1 Intervention

Participants will receive AMG 732 low dose SC.

Group III: Part B: AMG 732 High Dose Experimental Treatment 1 Intervention

Participants will receive AMG 732 high dose SC.

Group IV: Part A: AMG 732 Experimental Treatment 1 Intervention

Participants in 6 cohorts will receive either AMG 732 or placebo in Single Ascending Doses (SAD).

Group V: Part A: Placebo Placebo Group 1 Intervention

Participants in 6 cohorts will receive either AMG 732 or placebo in Single Ascending Doses (SAD).

Group VI: Part B: Placebo Placebo Group 1 Intervention

Participants will receive placebo 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

Published Research Related to This Trial

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 the first FDA-approved medication for treating thyroid eye disease (TED) and has shown efficacy in two randomized, double-masked, placebo-controlled trials, with favorable outcomes also reported in post-approval cases.

While teprotumumab is effective, it should be avoided during pregnancy and may exacerbate conditions like inflammatory bowel disease, worsen hyperglycemia, and cause hearing impairment, necessitating careful monitoring of at-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Teprotumumab in Thyroid Eye Disease. Teo, HM., Smith, TJ., Joseph, SS.[2021]

In a study of 2170 patients with thyroid-associated ophthalmopathy (TAO), the most common symptoms were proptosis (55.25%) and diplopia (33.09%), with restricted eye movements being the most frequent clinical sign (83.46%).

MRI was found to be more sensitive than clinical activity scores in determining the active phase of extraocular muscle involvement, with 71.99% of patients undergoing MRI showing active disease, highlighting its importance in diagnosing and assessing TAO.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical Analysis of 2 170 Cases of Thyroid-Associated Ophthalmopathy Involving Extraocular Muscles]. Yang, M., Du, BX., Wang, YJ., et al.[2023]

In a study of seven patients with thyroid-associated ophthalmopathy (TAO), thyroglobulin (Tg) was detected in retrobulbar fibroadipose tissue in four patients, suggesting a potential role for Tg in the autoimmune damage associated with TAO.

The presence of Tg in orbital tissues was linked to previous treatment with radioiodine, indicating that this treatment may influence the pathogenesis of TAO and supporting the hypothesis that Tg acts as a coantigen in the disease process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thyroglobulin in orbital tissues from patients with thyroid-associated ophthalmopathy: predominant localization in fibroadipose tissue. Lisi, S., Marinò, M., Pinchera, A., et al.[2022]

Thyroid-associated ophthalmopathy (TAO) is most commonly linked to hyperthyroidism, with a significant number of patients (88.8%) presenting with clinically inactive TAO, indicating a generally favorable prognosis.

In a study of 3620 patients, the condition often exhibited an asymmetric phenotype, particularly in euthyroid patients, and the majority experienced an active phase lasting less than 12 months, suggesting that early detection and individualized management are crucial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical features and clinical course of thyroid-associated ophthalmopathy: a case series of 3620 Chinese cases. Du, B., Wang, Y., Yang, M., et al.[2022]

In a study of 24 patients with thyroid eye disease (TED), 20.8% had elevated serum IgG4 levels indicative of IgG4-related disease (IgG4-RD) without any other systemic disease present.

Total IgG and IgG subclass levels were not reliable indicators for elevated thyroid stimulating immunoglobulin (TSI) levels, suggesting that IgG4 levels may play a unique role in a subset of TED patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serum total IgG and IgG4 levels in thyroid eye disease. Sy, A., Silkiss, RZ.[2020]

In a study of 2158 patients with thyroid-associated ophthalmopathy (TAO), those with euthyroidism (Eu-TAO) were found to be older and had a lower female-to-male ratio compared to those with hyperthyroidism (Hr-TAO) and hypothyroidism (Ho-TAO).

Eu-TAO patients exhibited more unilateral involvement and milder clinical symptoms, with only 8.56% showing clinically active TAO, compared to higher rates in Hr-TAO and Ho-TAO patients, indicating that Eu-TAO may present a less severe form of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical phenotypes of euthyroid, hyperthyroid, and hypothyroid thyroid-associated ophthalmopathy. Yang, M., Wang, Y., Du, B., et al.[2023]

Overt hyperthyroidism significantly increases the risk of developing age-related macular degeneration (AMD), with an odds ratio of 3.51, indicating more than three times the risk compared to those with normal thyroid function.

Current and past use of thyroxine medication in older adults is associated with a higher risk of incident AMD, with odds ratios of 1.68 and 1.91, respectively, suggesting a potential link between thyroid hormone treatment and AMD incidence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thyroid Dysfunction and Ten-Year Incidence of Age-Related Macular Degeneration. Gopinath, B., Liew, G., Kifley, A., et al.[2022]

In a study of 229 patients treated with amiodarone, 38.4% developed thyroid dysfunction, with 20.5% experiencing amiodarone-induced thyrotoxicosis (AIT) and 17.9% amiodarone-induced hypothyroidism (AIH), highlighting the need for careful monitoring in these patients.

The most significant risk factor for developing thyroid dysfunction was having pre-existing thyroid conditions, as these patients experienced dysfunction earlier than those with normal thyroid glands, indicating that prior thyroid issues should prompt more frequent monitoring during amiodarone treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amiodarone-induced thyroid dysfunction in an iodine-replete area: epidemiological and clinical data. Zosin, I., Balaş, M.[2017]

Euthyroid patients with thyroid-associated ophthalmopathy (TAO) exhibited a less active and severe clinical course compared to hyperthyroid patients, with lower clinical activity scores and less bilateral involvement.

Thyroid-stimulating hormone receptor antibodies (TRAbs) levels were significantly lower in euthyroid patients, suggesting that TSI may be a more sensitive marker for diagnosing euthyroid TAO compared to TBII.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical features of thyroid-associated ophthalmopathy in clinically euthyroid Korean patients. Jang, SY., Lee, SY., Lee, EJ., et al.[2022]

Teprotumumab significantly reduces proptosis (eye bulging) and inflammation in patients with chronic Thyroid Eye Disease (TED), with an average reduction of 3.5 mm in proptosis after treatment.

In a study of 31 patients who received an average of 7 infusions, 67% of those with diplopia (double vision) experienced a significant improvement, and there was a notable reduction in both muscle and fat tissue volume in the orbits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teprotumumab for the treatment of chronic thyroid eye disease. Ugradar, S., Kang, J., Kossler, AL., et al.[2022]

In an animal model, modified forms of thyroglobulin (TG) were tested, with the most effective being TG altered with diazonium derivatives, which successfully induced autoimmune thyroiditis.

In a small human trial involving eight patients with untreatable metastatic thyroid cancer, the therapy showed minimal toxicity and induced autoimmune thyroiditis in three patients, but the overall clinical response to the treatment was minimal and not significantly measurable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy of thyroid cancer by induction of autoimmune thyroiditis. Gerfo, PL., Feind, C., Weber, C., et al.[2013]

Alemtuzumab-induced thyroid eye disease (AI-TED) can present with greater severity compared to conventional thyroid eye disease (TED), as indicated by an average clinical activity score of 3.3 among 16 patients studied, with some experiencing scores as high as 5.0 during active phases.

AI-TED may develop several months after the onset of Graves' disease, highlighting the need for healthcare providers to monitor patients for potential severe TED following treatment with alemtuzumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alemtuzumab-Induced Thyroid Eye Disease: A Comprehensive Case Series and Review of the Literature. Nirmalan, A., Blecher, N., Hyder, S., et al.[2023]

In a study of 21 patients with thyroid eye disease (TED) treated with teprotumumab, 71.4% experienced a significant reduction in proptosis (eye bulging) of at least 2 mm, indicating the drug's efficacy in improving this symptom.

Teprotumumab also led to improvements in clinical activity scores and extraocular motility, suggesting it can benefit a wide range of TED patients, including those with stable or milder forms of the disease, although it may have limitations in addressing eyelid position and strabismus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Experience With the Clinical Use of Teprotumumab in a Heterogenous Thyroid Eye Disease Population. Diniz, SB., Cohen, LM., Roelofs, KA., et al.[2023]

Citations

1. synapse.patsnap.com synapse.patsnap.com/drug/36c53402035c4d5e9c0a54d5e3a333c1

AMG-732 - Drug Targets, Indications, Patents A Phase 1/2, Randomized, Double-Masked, Placebo-Controlled, Multicenter Study to Assess the Safety, Pharmacokinetics, and Efficacy of AMG 732 in Healthy ...

2. withpower.com withpower.com/trial/phase-1-eye-diseases-4-2024-d963b

AMG 732 for Thyroid Eye Disease The primary objective of Part A of this study is to investigate the safety and tolerability of AMG 732 after single subcutaneous (SC) doses.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06401044

NCT06401044 | A Study of AMG 732 in Healthy ... The primary objective of Part B of this study is to investigate the efficacy of AMG 732 in participants with Thyroid Eye Disease (TED) after multiple SC doses.

4. amgentrials.com amgentrials.com/study/?id=20230302

A Study of AMG 732 in Healthy Participants and ... The primary objective of Part B of this study is to investigate the efficacy of AMG 732 in participants with Thyroid Eye Disease (TED) after multiple SC doses.

5. finance.yahoo.com finance.yahoo.com/news/thyroid-eye-disease-clinical-trial-170000643.html

Thyroid Eye Disease Clinical Trial Pipeline Gains Momentum Lundbeck's proof-of-concept (PoC) trial will evaluate the efficacy, safety, and tolerability of Lu AG22515 as a potential treatment for Thyroid ...

6. theglobeandmail.com theglobeandmail.com/investing/markets/stocks/AMGN/pressreleases/35738839/amgens-promising-new-study-on-thyroid-eye-disease-treatment/

Amgen's Promising New Study on Thyroid Eye Disease ... The study aims to evaluate the safety and efficacy of AMG 732, a potential treatment for Thyroid Eye Disease (TED), in both healthy participants ...

7. app.trialscreen.org app.trialscreen.org/trials/phase-1-amg-732-healthy-participants-thyroid-eye-disease-trial-nct06401044

A Phase 1 study of AMG 732 in healthy participants and ... The main goal of this study is to evaluate the safety and tolerability of a new investigational drug called AMG 732 when given as a single injection under the ...