Phase 1 study to assess the safety and biological activity of ATX-GD-59 in patients with Graves Disease not currently treated with anti-thyroid therapy. This will be an open label dose titration involving injections on 10 occasions, each two weeks apart. After dosing is complete there will be a 12 week follow up period. Blood samples will be drawn throughout the study to monitor safety and the body's response to the injections. Thyroid function will be measured throughout the trial to monitor Graves disease progression.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Disease specific immune modulating treatment for Graves Disease
Queen Elizabeth Hospital
Birmingham, United Kingdom
University Hospital of Wales
Cardiff, United Kingdom
Royal Devon and Exeter Hospital
Exeter, United Kingdom
St James's University Hospital
Leeds, United Kingdom
Occurrence of Treatment Emergent Adverse Events (TEAE), Serious Adverse Events (SAE), and Laboratory Abnormalities up to Week 22 Compared to Baseline.
An adverse event (AE) was defined as any untoward medical occurrence in a subject administered study drug that did not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavourable and unintended sign, symptom, disease or outcome of death temporally associated with the use of study drug, whether or not considered causally related to the study drug. Treatment emergent adverse events (TEAEs) were any AE that started or worsened in severity on or after the first administration of study drug up to and including 28 days after the last administration of study drug. Relationship, as indicated by the Investigator, was classified as 'not related', 'possibly related', 'probably related' or 'definitely related' (increasing severity of relationship). A drug related AE was defined as an AE with a relationship to study drug of 'possibly related', 'probably related' or 'definitely related' or with a missing or unknown relationship to study drug
Time frame: 22 weeks
Change in Serum Anti-TSHR Antibodies From Baseline to Week 22 - Measured by TSHR-binding Inhibitory Immunoglobulin (TBII)
TSHR-binding inhibitory immunoglobulin (TBII) are autoantibodies directed against the TSH receptor. TBII is used clinically for the differential diagnosis and management of Graves' Disease.
Time frame: Weeks 18, 22 and 30
Change in Serum Anti-TSHR Antibodies From Baseline to Week 22 - Measured by Stimulatory TSHR Antibodies (TSAb)
Stimulatory TSHR antibodies (TSAb) assays were measured using cell-based methods described by Leschik et al. TSAb activity is measured by calculating percentage specimen-to-reference ratio (%SRR).
Time frame: Weeks 18, 22 and 30
Change in Serum Anti-TSHR Antibodies From Baseline to Week 22 - Measured by Blocking TSHR Antibodies (TBAb)
Blocking TSHR antibodies (TBAb) assays were measured using cell-based methods described by Leschik et al. TBAb activity is measured by calculating percentage inhibition.
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Hammersmith Hospital
London, United Kingdom
Kings College Hospital
London, United Kingdom
The Christie
Manchester, United Kingdom
Royal Victoria Infirmary
Newcastle, United Kingdom
Time frame: Weeks 18, 22 and 30
Change in Serum Free Triiodothyronine (fT3) From Baseline to Week 22.
Serum fT3 was measured centrally from screening to the final week 30 follow-up visit. Baseline was fT3 value at study day 1.
Time frame: Weeks 18, 22 and 30
Change in Serum Free Thyroxine (T4) From Baseline to Week 22.
Serum fT4 was measured centrally from screening to the final week 30 follow-up visit. Baseline was fT4 value at study day 1.
Time frame: Weeks 18, 22 and 30
Change in Serum Thyroid Stimulating Hormone (TSH) From Baseline to Week 22.
Serum TSH was measured centrally from screening to the final week 30 follow-up visit. Baseline was fT4 value at study day 1.
Time frame: Weeks 18, 22 and 30
Change From Baseline in Peripheral Blood Mononuclear Cell (PBMC) T Cell Activity
Time frame: weeks 0, 18 and 22
Change From Baseline in IL-10 mRNA Expression in PBMCs
Time frame: weeks 0, 18 and 22
Change From Baseline in Biomarker Signature of PBMC Cells
Time frame: weeks 0, 18 and 22