An Open-label, Rollover Study to Evaluate the Efficacy and Safety of AMG 732 in Participants 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]

Decision date (initial)

2026-05-25

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Amgen Inc.

External identifiers

EU CT number

2025-523280-38-00

WHO UTN

U1111-1331-1820

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety

To assess the efficacy of AMG 732 in participants with thyroid eye disease (TED) who are defined as primary nonresponders or relapsed during the safety follow-up in the parent study

Secondary objectives 5

1. To assess the efficacy of AMG 732 in participants with TED who are defined as primary nonresponders or relapsed during the safety follow- up in the parent study
2. To characterize pharmacokinetics (PK) of AMG 732 in participants with TED
3. To investigate the safety and tolerability of AMG 732
4. To assess the efficacy of AMG 732 in participants with TED who had relapse after achieving proptosis response in the parent study at week 9999
5. To assess the efficacy of AMG 732 in participants with TED who are defined as primary nonresponders in the parent study at week 9999

Conditions and MedDRA coding

Thyroid Eye Disease

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Signed informed consent
2. Age≥18 years at the time of signing informed consent for parent study
3. Moderate-to-severe TED at the time of enrollment in parent study and does not require immediate surgical ophthalmological intervention and is not planning corrective surgery/irradiation during the rollover trial
4. Any worsening in thyroid status should be corrected to maintain euthyroid status for the entire rollover study
5. Participants must use protocol-specified contraception,during treatment and for an additional 6 months after the last dose of trial intervention
6. Participants with TED who completed Amgen sponsored clinical trial of AMG 732

Exclusion criteria 28

1. Corneal decompensation unresponsive to medical management in the study eye
2. Known positive test for human immunodeficiency virus (HIV) (HIV-1 and HIV-2) antibody at screening or within the last 12 months
3. Presence or history of viral hepatitis infection: • Active hepatitis C infection (participants with detectable hepatitis C antibody [HCVAb] and hepatitis C virus [HCV] RNA viral load above the limit of quantification)  Participants with presence of HCVAb and HCV RNA viral load below the limit of quantification (HCV RNA negative) with or without prior treatment are allowed. • Active hepatitis B infection (presence of hepatitis B surface antigen [HBsAg] and hepatitis B virus [HBV] DNA viral load above the limit of quantification [HBV DNA positive])  Participants with resolved HBV infection defined as absence of HBsAg and presence of HBV core antibody (HBcAb) followed by an HBV DNA viral load below the limit of quantification (HBV DNA negative) are allowed, with a requirement for regular monitoring for reactivation for the duration of treatment on the study and assessing the need for HBV prophylaxis therapy per local or institutional guidelines.  Participants with chronic HBV infection inactive carrier state defined as presence of HBsAg and HBV DNA viral load below the limit of quantification (HBV DNA negative) are allowed, with a requirement for regular monitoring for reactivation for the duration of treatment on the study and assessing the need for HBV prophylaxis therapy per local or institutional guidelines
4. Participants have had an adverse event of hearing impairment during the parent study, and which is not recovered or resolved
5. Participants had major surgery within 8 weeks before the first dose of study drug or plans to have elective surgery from screening through EOS
6. Participants with a history of inflammatory bowel disease (IBD), such as ulcerative colitis or Crohn’s disease
7. Known hypersensitivity to any of the components of TEPEZZA, AMG 732, or prior hypersensitivity reactions to fully human mAbs
8. Any treatment with rituximab (Rituxan® or MabThera®), tocilizumab (Actemra® or Roactemra®), or any other nonsteroid immunosuppressive agent during or after completion of parent study
9. Have received an investigational agent for any condition (including TED) after the completion of parent study
10. Participant unlikely to be able to complete all protocol-required procedures, restrictions and requirements, in the judgment of the individual and investigator
11. History or evidence of any other clinically significant disorder, condition, or disease that, in the opinion of the investigator, would pose a risk to participant safety
12. Active liver disease, hepatic dysfunction or kidney dysfunction at screening, as determined by:  alanine aminotransferase (ALT) or aspartate aminotransferase (AST) concentrations > 3 times upper limit of normal (ULN) at screening  glomerular filtration rate ≤ 30 mL/min/1.73 m2 at screening
13. Currently pregnant (confirmed with positive pregnancy test) or breastfeeding or planning to become pregnant, donate eggs or breastfeed while on trial until an additional 6 months after the last dose of study drug
14. Female participants of childbearing potential unwilling to use protocol-specified method of contraception during treatment and for an additional 6 months after the last dose of trial intervention (AMG 732)
15. Male participants with a female partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use contraception during treatment and for an additional 6 months after the last dose of study drug
16. Male participants with a pregnant partner who are unwilling to practice abstinence or use a condom during treatment and for an additional 6 months after the last dose of study drug
17. Male participants unwilling to abstain from donating sperm during treatment and for an additional 6 months after the last dose of trial intervention
18. Participants developed any adverse event that is considered related to AMG 732 which required study drug interruption/discontinuation in the parent study. If a participant prematurely discontinues AMG 732 for reasons other than safety/tolerability reasons and completed the parent study, may be eligible for the study after consultation with medical monitor
19. Prior orbital irradiation or orbital decompression in the study eye during or after the completion of parent study
20. Prior adult strabismus surgery
21. Anticipated use of another investigational agent for any condition during the course of the study
22. Any other new development of the disease/condition/significant laboratory test abnormality during the course of the parent study, in the opinion of the Investigator, that would potentially put the participant at unacceptable risk
23. Participant has known sensitivity to any of the products or components to be administered during dosing
24. Malignancy (except curatively treated nonmelanoma skin cancers, curatively treated cervical carcinoma in situ, or curatively treated breast ductal carcinoma in situ) within the last 5 years before signing the informed consent
25. Donated blood or had significant blood loss or received a transfusion of any blood or blood products within 9999 days before day 1 dosing or received a plasma donation within 9999 days before day 1 dosing
26. Steroids (intravenous, oral, or injected) and steroid eye drops within 9999 weeks before the first dose of study drug. Systemic steroid use (intravenous, injected, or oral) and steroid eye drops are not to be initiated during the study; however, topical (excluding ophthalmologic), and inhaled steroids for conditions other than TED are allowed. Short course of steroids for the treatment of injection-associated reaction and exacerbation of asthma are allowed
27. Treatment with any mAb except the study drugs in parent study within 9999 months before the first dose of study drug
28. Use of selenium is restricted during the duration of rollover study and within 9999 weeks before the first dose of study drug. Selenium must not be restarted during the study; however, taking a multivitamin that includes selenium (less than 9999 µg daily) is allowed

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proptosis response status in the study eye (responders are defined as participants with a ≥ 2 mm reduction from baseline in the study eye without deterioration [≥ 2 mm increase] of proptosis in the fellow eye) at week 9999

Secondary endpoints 4

1. PK parameters including but not limited to trough concentration (Ctrough), maximum observed concentration (Cmax), time to maximum observed concentration (tmax), area under the concentration-time curve (AUC) over the dosing interval, and if feasible, half-life (t1/2) as data permits
2. Incidence of treatment-emergent adverse events, treatment-emergent serious adverse events, adverse events leading to investigational product discontinuation, and events of interest (EOIs)
3. Change from baseline at week 9999 in proptosis measurement by an exophthalmometer in the study eye
4. Proptosis response status in the study eye at week 9999 -Change from baseline at week 9999 in proptosis measurement by an exophthalmometer in the study eye

Investigational products

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

Test 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

2 EU/EEA countries · 4 investigational sites

By country

Investigational sites

Results and documents

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

Documents 18 files

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

Application history

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