Graves Disease, Graves' Disease
Conditions
Brief summary
The main purpose of this study is to look at how efgartigimod affects thyroid function in adults with Graves' Disease (GD). The study will also check whether efgartigimod is safe and well tolerated. It will look at how efgartigimod is distributed and eliminated in the body, how it changes antibody levels, and how the immune system responds to it. The study consists of a part A double-blinded treatment period, a part B treatment/observation period and a part C open-label treatment/observation period. During the part A and part B treatment periods, participants will receive efgartigimod PH20 SC via Prefilled Syringe (PFS) or placebo. During the part C open-label treatment period, participants will receive efgartigimod PH20 SC PFS. Participation in the different parts of the study will depend on the participant's response to treatment. The total study duration for participants ranges from 63 to 135 weeks, depending on the response to treatment. More information can be found here: https://clinicaltrials.argenx.com/vitalithy
Interventions
BIOLOGICALEfgartigimod PH20 SC
Subcutaneous injection of Efgartigimod PH20 Via Prefilled Syringe (PFS)
OTHERPlacebo PH20 SC
Subcutaneous injection of placebo PH20 via Prefilled Syringe (PFS)
Sponsors
argenx
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Is at least 18 years of age and the local legal age of consent for clinical studies when signing the ICF. * Has a documented diagnosis of GD with TRAb (anti-thyrotropin receptor antibody) levels \>=ULN (upper limit of normal) at screening. * Has active hyperthyroidism due to GD with TSH (thyroid-stimulating hormone) \<0.1 mIU/L at screening. * Has been treated with MMI (methimazole) or CBZ (carbimazole) for at least 3 months before screening.
Exclusion criteria
* History of hyperthyroidism not caused by GD (eg, toxic adenoma or toxic multinodular goiter). * History of RAI (radioactive iodine) therapy or received a total thyroidectomy. * T3- or T4-containing medication or supplement (eg, levothyroxine, liothyronine, desiccated thyroid preparations, or thyroid-support supplements) received \<6 weeks before screening. * Any complication of hyperthyroidism or underlying medical condition that would put the participant at undue risk. This includes arrhythmia or tachyarrhythmia related to GD, such as atrial fibrillation or atrial flutter not sufficiently controlled with medications. * Graves' orbitopathy/Thyroid Eye Disease (GO/TED) requiring systemic therapy (eg, corticosteroids), orbital injections, orbital surgery, or orbital radiation, or expected immediate surgical intervention and/or planned corrective surgery/irradiation or medical therapy during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants who are euthyroid (fT3, fT4, and TSH within normal ranges) off ATDs at week 24 in part A | Up to 24 weeks (part A) | Free triiodothyronine: \[fT3\]; free thyroxine: \[fT4\]; ATDs: antithyroid drugs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to becoming euthyroid off ATDs in part A | Up to 24 weeks (part A) | ATDs: antithyroid drugs |
| Percentage of participants who are euthyroid and receiving MMI ≤5 mg/day or CBZ ≤7.5 mg/day at week 24 in part A | Up to 24 weeks (part A) | MMI: methimazole (also known as thiamazole); CBZ: carbimazole. |
| Percentage of participants with fT3 and fT4 levels below the ULN off ATDs at week 24 in part A | Up to 24 weeks (part A) | ULN : upper limit of normal; ATDs: antithyroid drugs. |
| Percentage of participants who are euthyroid off ATDs and TRAb seronegative at week 24 in part A | Up to 24 weeks (part A) | TRAb: anti-TSHR autoantibodies; ATDs: antithyroid drugs. |
| Time to becoming euthyroid off ATDs and TRAb seronegative | Up to 24 weeks (part A) + up to 135 weeks | ATDs: antithyroid drugs; TRAb: anti-TSHR autoantibodies. |
| Time to becoming euthyroid and receiving an ATD dose of MMI ≤5 mg/day or CBZ ≤7.5 mg/day (part A) | Up to 24 weeks (Part A) | ATDs: antithyroid drugs; MMI: methimazole (also known as thiamazole); CBZ: carbimazole. |
| Time to becoming euthyroid | Up to 24 weeks (part A) + up to 135 weeks | — |
| Time to having TSH within normal ranges among participants who have TSH lower than the LLN at baseline (part A) | Up to 24 weeks (part A) | TSH: thyroid-stimulating hormone; LLN: lower limit of normal. |
| Percentage of participants who remain euthyroid without ATDs | Up to 74 weeks (part B) | ATDs: antithyroid drug |
| Percentage of participants who remain euthyroid without ATDs and without efgartigimod PH20 SC PFS for 6, 12, and 18 months | Up to 74 weeks (part B) + up to 135 weeks | ATDs: antithyroid drug |
| Percentage of participants who remain euthyroid without ATDs and without efgartigimod PH20 SC PFS | Up to 72 weeks (part C) | ATDs: antithyroid drug |
| Incidence of AEs and SAEs | Up to 135 weeks | AEs: adverse events ; SAEs: serious adverse events. |
| Change in ThyPRO-39 over time | Up to 135 weeks | The Thyroid-Specific Patient-Reported Outcome Short Form (ThyPRO-39) 39 item version of the ThyPRO. Each item is related to a specific aspect of the participant's experience with their thyroid condition. Each item is scored on a 5-point Likert scale, and the scores are then transformed to a 0-to-100 scale. Higher scores indicate worse health status. |
| Change in PROMIS-PF10a over time | Up to 135 weeks | The Patient-Reported Outcomes Measurement Information System Physical Function-10 item (PROMIS-PF10a) is a self-administered physical functioning assessment comprising 10 items that measure respondents' ability to perform common physical tasks. Scoring involves summing the numerical responses to each item; higher scores indicate better physical function. |
| Efgartigimod serum concentrations over time | Up to 24 weeks (part A) + 72 weeks (part C) | — |
| Percentage change from baseline in total IgG levels in serum over time | Up to 98 weeks | IgG: immunoglobulin G |
| Percentage change from baseline in TRAb serum levels over time | Up to 135 weeks | TRAb: anti-TSHR autoantibodies. |
| Incidence of ADA against efgartigimod in serum | Up to 24 weeks (part A) + up to 135 weeks | ADA: antidrug antibody(ies) |
| Incidence of antibodies against rHuPH20 in plasma | Up to 24 weeks (part A) + Up to 135 weeks | rHuPH20: recombinant human hyaluronidase PH20 |
| Incidence of NAb against efgartigimod in serum and rHuPH20 in plasma | Up to 24 weeks (part A) + up to 135 weeks | NAb: neutralizing antibody(ies); rHuPH20: recombinant human hyaluronidase PH20. |
Countries
Georgia, United States
Contacts
CONTACTSabine Coppieters, MD
Outcome results
None listed