A Phase 1/2 Study to Assess AMG 732 in Healthy Subjects and Subjects with Thyroid Eye Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amgen Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

22 Oct 2025 → ongoing

Decision date (initial)

2025-09-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Amgen Inc.

External identifiers

EU CT number

2024-514110-12-00

WHO UTN

U1111-1309-5340

ClinicalTrials.gov

NCT06401044

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety

To investigate the efficacy of AMG 732 in subjects with TED after multiple subcutaneous doses

Secondary objectives 5

1. To investigate the safety and tolerability of AMG 732 after multiple subcutaneous doses
2. To assess the pharmacokinetics (PK) of AMG 732 after multiple subcutaneous doses
3. To characterize the immunogenicity of AMG 732 after multiple subcutaneous doses
4. To further investigate the efficacy of AMG 732 in subjects with TED after multiple subcutaneous doses
5. To evaluate the effect of AMG 732 on the quality of life (QoL) of subjects with TED using the GO-QoL Visual Functioning (VF) and Appearance (A) subscale scores

Conditions and MedDRA coding

Thyroid Eye Disease

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request. Information on IPD sharing Access Criteria Time Frame and supporting Information Type is avaialble on the Amgen Clinical Trials portal (http://www.amgen.com/datasharing).

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Subject has provided informed consent before initiation of any study-specific activities/procedures.
2. Male or female aged 18 to 55 years for Part A and male or female aged 18 to 65 years for Part B 65 years for Part B, inclusive, at the time of informed consent.
3. Part B only: Moderate-to-severe active TED (not sight-threatening but has an appreciable impact on daily life), usually associated with 2 or more of the following: lid retraction ≥ 2 mm, moderate or severe soft tissue involvement, exophthalmos ≥ 3 mm above normal for race and gender, and inconstant or constant diplopia.
4. Part B only: Subject had onset of active TED symptoms (as determined by subject records) within 15 months prior to baseline
5. Part B only: Clinical diagnosis of Graves disease associated with active TED with a CAS ≥ 3 (on the 7-item scale) for the most severely affected eye at screening and baseline
6. Part B only: Proptosis ≥ 18 mm in the study eye at baseline.
7. Part B Only: Subjects with baseline subjective binocular diplopia score > 0
8. Part B Only: Subjects must be euthyroid with the baseline disease under control or have mild hypo or hyperthyroidism (defined as free thyroxine and free triiodothyronine levels < 50% below or above the normal limits) at screening. Every effort should be made to correct the mild hypo or hyperthyroidism promptly and to maintain the euthyroid state for the full duration of the trial.
9. Part B Only: Does not require immediate surgical ophthalmological intervention and is not planning corrective surgery/irradiation during the trial

Exclusion criteria 11

1. Malignant condition in the past 12 months (except successfully treated basal/squamous cell carcinoma of the skin or cervical cancer in situ)
2. History or evidence of any other clinically significant disorder, condition, or disease (except for those outlined in this section) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety, or interfere with the study evaluation, procedures or completion.
3. Part B only: Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, 9999) to the best of the subject and investigator’s knowledge, except when an eligible patient is contraindicated for 9999 in which case 9999 is not required. Also when subject did not consent for 9999 is not required.
4. Subjects with a history of 9999, such as 9999.
5. Laboratory Parameters for active liver disease, hepatic dysfunction or 9999 as determined by Part A: ALT or aspartate aminotransferase (AST) levels > 1.5 times upper limit of normal (ULN) Part B: ALT or AST levels > 3 times ULN or glomerular filtration rate ≤ 30 mL/min/1.73 m2 at screening. 9999
6. Positive test for hepatitis B serology at screening defined as: (1) positive for hepatitis B surface antigen (HBsAg); OR (2) positive for hepatitis B core antibody (HBcAb). Patients HBsAg negative, hepatitis B surface antibody (HBsAb) positive and HBcAb negative due to vaccination are eligible for the study. Patients HBsAg negative and HBsAb positive for which the cause cannot be determined as vaccination will be considered ineligible for the study
7. Positive test for human immunodeficiency virus (HIV) or hepatitis C virus (HCV) antibody at screening or within the last 12 months. Subjects successfully treated for an HCV infection are allowed to participate if a sustained virologic response was achieved, defined as aviremia 24 weeks after completion of the antiviral therapy.
8. Subject tested positive for alcohol and/or drugs of abuse at screening
9. Part A: History of substance abuse (eg, alcohol, nicotine or tobacco, and licit or illicit drugs) within 12 months before screening. Part B only: History of substance abuse (eg, alcohol and illicit drugs) within 12 months before screening.
10. The subject has a major surgery within 8 weeks prior to the first dose of study drug or plans to have an elective surgery from screening through end of study.
11. Donated blood, or had significant blood loss, or received a transfusion of any blood or blood products within 60 days prior to day 1 dosing or received a plasma donation within 7 days prior to day 1 dosing.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline at week 9999 in proptosis measurement by an exophthalmometer in the study eye

Secondary endpoints 6

1. Subject incidence of treatment-emergent adverse events, including serious adverse events
2. PK parameters including but not limited to maximum observed concentration (Cmax), time to maximum observed concentration (Tmax), area under the concentration time curve (AUC) over the dosing interval, accumulation following multiple dosing, and if feasible, half-life (t1/2) as data permits.
3. Subject incidence of antidrug antibodies (ADAs)
4. Proptosis response status in the study eye 9999 proptosis in the fellow eye) at week 9999
5. Mean change from Baseline at Week 9999 in the GO-QoL Visual Functioning (VF) subscale score
6. Mean change from Baseline at Week 9999 in the GO-QoL Appearance (A) subscale score

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amgen Inc.

Sponsor organisation

Amgen Inc.

Address

1 Amgen Center Drive

City

Thousand Oaks

Postcode

91320-1730

Country

United States

Scientific contact point

Organisation

Amgen Inc.

Contact name

Medical Information

Public contact point

Organisation

Amgen Inc.

Contact name

Medical Information

Third parties 6

Locations

6 EU/EEA countries · 22 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 85 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications