AMG 732 for Thyroid Eye Disease

Overseen By Amgen Call Center

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

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

48 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary objective of this study is to investigate the safety and tolerability of AMG 732 after single subcutaneous (SC) doses.

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.

What data supports the idea that AMG 732 for Thyroid Eye Disease is an effective treatment?

The available research does not provide specific data on AMG 732 for Thyroid Eye Disease. Instead, it mentions other treatments like teprotumumab, which has been shown to significantly reduce the signs of active Thyroid Eye Disease. Without direct data on AMG 732, we cannot compare its effectiveness to other treatments. ^{1 2 3 4 5}

What safety data is available for AMG 732 in treating Thyroid Eye Disease?

The research provided does not mention AMG 732, AMG-732, HZN-280, or HZN280 specifically. However, it discusses teprotumumab, a treatment for Thyroid Eye Disease, which may be related. Teprotumumab has been associated with adverse events such as exacerbation of pre-existing inflammatory bowel disease, worsening hyperglycemia, and hearing impairment. Patients at risk for these adverse events should be closely monitored. No specific safety data for AMG 732 is available in the provided research. ^{6 7 8 9 10}

Is the drug AMG 732 a promising treatment for Thyroid Eye Disease?

Yes, AMG 732 is considered a promising drug for treating Thyroid Eye Disease because it is being actively studied and developed, indicating potential benefits for patients with this condition. ^{2 11 12 13 14}

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: 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 II: Part A: Placebo Placebo Group 1 Intervention

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

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

Findings from Research

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]

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 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]

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 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]

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]

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]

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 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]

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]

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]

References

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

Alemtuzumab-Induced Thyroid Eye Disease: A Comprehensive Case Series and Review of the Literature. [2023]

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

Clinical features and clinical course of thyroid-associated ophthalmopathy: a case series of 3620 Chinese cases. [2022]

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

Early Experience With the Clinical Use of Teprotumumab in a Heterogenous Thyroid Eye Disease Population. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Clinical features of thyroid-associated ophthalmopathy in clinically euthyroid Korean patients. [2022]

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

Teprotumumab for the treatment of chronic thyroid eye disease. [2022]

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

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

7. Poland pubmed.ncbi.nlm.nih.gov

Amiodarone-induced thyroid dysfunction in an iodine-replete area: epidemiological and clinical data. [2017]

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

Efficacy and Safety of Teprotumumab in Thyroid Eye Disease. [2021]

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

Thyroid Dysfunction and Ten-Year Incidence of Age-Related Macular Degeneration. [2022]

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

Immunotherapy of thyroid cancer by induction of autoimmune thyroiditis. [2013]

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

Serum total IgG and IgG4 levels in thyroid eye disease. [2020]

12. Germany pubmed.ncbi.nlm.nih.gov

Clinical phenotypes of euthyroid, hyperthyroid, and hypothyroid thyroid-associated ophthalmopathy. [2023]

13. China pubmed.ncbi.nlm.nih.gov

[Clinical Analysis of 2 170 Cases of Thyroid-Associated Ophthalmopathy Involving Extraocular Muscles]. [2023]

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

Thyroglobulin in orbital tissues from patients with thyroid-associated ophthalmopathy: predominant localization in fibroadipose tissue. [2022]