A Study to Assess Efficacy and Safety of Efgartigimod PH20 SC PFS in Adult Participants With Graves' Disease

Phase 3RecruitingNCT07570316

argenx230 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

230

Conditions

Graves' Disease Graves Disease

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Percentage of participants who are euthyroid (fT3, fT4, and TSH within normal ranges) off ATDs at week 24 in part A

Free triiodothyronine: \[fT3\]; free thyroxine: \[fT4\]; ATDs: antithyroid drugs

Time frame: Up to 24 weeks (part A)

Secondary Outcomes

Time to becoming euthyroid off ATDs in part A

ATDs: antithyroid drugs

Time frame: Up to 24 weeks (part A)

Percentage of participants who are euthyroid and receiving MMI ≤5 mg/day or CBZ ≤7.5 mg/day at week 24 in part A

MMI: methimazole (also known as thiamazole); CBZ: carbimazole.

Time frame: Up to 24 weeks (part A)

Percentage of participants with fT3 and fT4 levels below the ULN off ATDs at week 24 in part A

ULN : upper limit of normal; ATDs: antithyroid drugs.

Time frame: Up to 24 weeks (part A)

Percentage of participants who are euthyroid off ATDs and TRAb seronegative at week 24 in part A

TRAb: anti-TSHR autoantibodies; ATDs: antithyroid drugs.

Time frame: Up to 24 weeks (part A)

Time to becoming euthyroid off ATDs and TRAb seronegative

ATDs: antithyroid drugs; TRAb: anti-TSHR autoantibodies.

Time frame: Up to 24 weeks (part A) + up to 135 weeks

Time to becoming euthyroid and receiving an ATD dose of MMI ≤5 mg/day or CBZ ≤7.5 mg/day (part A)

ATDs: antithyroid drugs; MMI: methimazole (also known as thiamazole); CBZ: carbimazole.

Time frame: Up to 24 weeks (Part A)

Time to becoming euthyroid

Time frame: 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)

TSH: thyroid-stimulating hormone; LLN: lower limit of normal.

Time frame: Up to 24 weeks (part A)

Percentage of participants who remain euthyroid without ATDs

ATDs: antithyroid drug

Time frame: Up to 74 weeks (part B)

Percentage of participants who remain euthyroid without ATDs and without efgartigimod PH20 SC PFS for 6, 12, and 18 months

ATDs: antithyroid drug

Time frame: Up to 74 weeks (part B) + up to 135 weeks

Percentage of participants who remain euthyroid without ATDs and without efgartigimod PH20 SC PFS

ATDs: antithyroid drug

Time frame: Up to 72 weeks (part C)

Incidence of AEs and SAEs

AEs: adverse events ; SAEs: serious adverse events.

Time frame: Up to 135 weeks

Change in ThyPRO-39 over time

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.

Time frame: Up to 135 weeks

Change in PROMIS-PF10a over time

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.

Time frame: Up to 135 weeks

Efgartigimod serum concentrations over time

Time frame: Up to 24 weeks (part A) + 72 weeks (part C)

Percentage change from baseline in total IgG levels in serum over time

IgG: immunoglobulin G

Time frame: Up to 98 weeks

Percentage change from baseline in TRAb serum levels over time

TRAb: anti-TSHR autoantibodies.

Time frame: Up to 135 weeks

Incidence of ADA against efgartigimod in serum

ADA: antidrug antibody(ies)

Time frame: Up to 24 weeks (part A) + up to 135 weeks

Incidence of antibodies against rHuPH20 in plasma

rHuPH20: recombinant human hyaluronidase PH20

Time frame: Up to 24 weeks (part A) + Up to 135 weeks

Incidence of NAb against efgartigimod in serum and rHuPH20 in plasma

NAb: neutralizing antibody(ies); rHuPH20: recombinant human hyaluronidase PH20.

Time frame: Up to 24 weeks (part A) + up to 135 weeks

A Study to Assess Efficacy and Safety of Efgartigimod PH20 SC PFS in Adult Participants With Graves' Disease

Overview

Conditions

Interventions

Eligibility

Locations (26)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts