A phase III, randomized, controlled, open label, no profit, single-center intervention study to compare the effect of a conservative (antithyroid drugs) and an ablative approach (radioiodine or total thyroidectomy) for the treatment of hyperthyroidism in patients with Graves’ disease and moderate-to-severe and active Graves’ Orbitopathy (GO) treated with intravenous glucocorticoids (ABLAGO Study)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Azienda Ospedaliero Universitaria Pisana

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hormonal diseases [C19]

Decision date (initial)

2024-11-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Associazione Allievi Endocrinologia Pisana

External identifiers

EU CT number

2024-518452-23-00

EudraCT number

2020-002721-28

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

To compare the effects of a conservative approach (antithyroid drugs, ATDs, experimental arm) vs
an ablative approach (radioiodine or total thyroidectomy) of thyroid treatment on the overall
outcome of GO in patients with GD and moderate-to-severe and active GO treated with
intravenous glucocorticoids at 24 weeks.

Conditions and MedDRA coding

Graves' disease and Graves' orbitophaty

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Patients willing and capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form 2. A diagnosis of Graves’ disease based on the presence of hyperthyroidism associated with detectable anti-thyrotropic hormone (TSH) receptor autoantibodies (TRAb). Patients must be euthyroid under control on stable medical regimen and every effort will be made to maintain the euthyroid status for the entire duration of the clinical trial. 3. Duration of Graves’ disease shorter than 18 months 4. A moderate-to-severe GO, defined as the presence of at least two of the following criteria in the most affected eye: an exophthalmos ≥3 mm compared with normal values for sex and race; presence of inconstant to constant diplopia; a lid retraction ≥2 mm; active GO (see below) 5. Active GO: CAS ≥ 3 out of 7 points in the most affected eye. Taking into account severity (moderate-to-severe) and activity (CAS ≥ 3/7) of GO, patients are eligible for methylprednisolone treatment according to clinical practice. 6. Duration of GO shorter than 18 months 7. AST, ALT and CPK levels ≤ 3 times the upper value of normal range 8. Absolute neutrophil count >1000 cells/L 9. Women of childbearing potential (WOCBP, namely not in menopause or in menopause since less than two years; in all other instances women will be considered as non-WOCBP) and men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year (as indicated in Appendix) for at least 6 and 7,5 months, respectively, after the last dose of the investigational drug (see also 2014_09_HMA_CTFG_Contraception.pdf, namely the “2014 CTFG Recommendations related to contraception and pregnancy testing in clinical trials”) 10. Male and female patients of age 18-75 years

Exclusion criteria 1

1. 1. Optic neuropathy or sight threatening GO of any type 2. Previous therapy for Graves’ disease with radioiodine or thyroidectomy 3. Corticosteroids or other immunosuppressive treatment for GO or other reasons in the last 3 months. 4. Previous surgical treatment and/or radiotherapy for GO. 5. Contraindications to GC: hypersensitivity to the active substance or to any of the excipients; uncontrolled hypertension, uncontrolled diabetes; history of peptic ulcer; urinary infections, glaucoma, systemic fungal infections, systemic infections unless appropriate therapy is employed, idiopathic thrombocytopenic purpura, cerebral edema associated with malaria. 6. Contraindications to RAI. 7. Previous or current glucocorticoid-related psychosis. 8. Use of medications interfering with GC or increasing the risk of GC-related adverse events (see prohibited therapies) 9. Acute or chronic liver disease 10. Contraindications to MMI: hypersensitivity to the active substance or to any of the excipients; breastfeeding 11. Contraindications of any kind to perform thyroidectomy 12. Relevant Malignancy 13. Recent (≤1 year) history of alcoholism or drug abuse 14. Mental illness that prevent patients from comprehensive, written informed consent 15. Pregnancy or breastfeeding

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Response rate 24 weeks after inclusion: -Comparison of overall GO outcome determined using a composite evaluation as indicated below. The evaluation will be performed by a unblinded ophthalmologist and will be documented in the CRF, including the following items: -Lid aperture in mm - CAS (5 items) -Exophthalmos in mm using a Hertel exophthalmometer -Eye ductions -Visual acuity using the Snellen chart in log10

Investigational products

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

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Azienda Ospedaliero Universitaria Pisana

Sponsor organisation

Azienda Ospedaliero Universitaria Pisana

Address

Via Paradisa 2

City

Pisa

Postcode

56124

Country

Italy

Scientific contact point

Organisation

Azienda Ospedaliero Universitaria Pisana

Contact name

Clinical Trial Center

Public contact point

Organisation

Azienda Ospedaliero Universitaria Pisana

Contact name

Clinical Trial Center

Locations

1 EU/EEA country · 1 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 6 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