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

A Phase 3, Randomized, Double-Masked, Placebo-Controlled, Multicenter Study Evaluating the Efficacy and Safety of Efgartigimod PH20 SC PFS in Adult Participants With Graves' Disease Inadequately Controlled With Antithyroid Drugs

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Graves Disease; Graves' Disease
• Intervention / Treatment: Biological: Efgartigimod PH20 SC; Other: Placebo PH20 SC

• Study Type: Interventional
• Enrollment (Estimated): 230
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Sabine Coppieters, MD; Phone Number: 857-350-4834; Email: clinicaltrials@argenx.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A - efgartigimod PH20 SC PFS; Participants will receive efgartigimod PH20 SC Via Prefilled Syringe (PFS) during the part A double-blinded treatment period.	Biological: Efgartigimod PH20 SC; Subcutaneous injection of Efgartigimod PH20 Via Prefilled Syringe (PFS)
Placebo Comparator: Part A - placebo PH20 SC PFS; Participants will receive placebo PH20 SC Via Prefilled Syringe (PFS) during the part A double-blinded treatment period.	Other: Placebo PH20 SC; Subcutaneous injection of placebo PH20 via Prefilled Syringe (PFS)
Experimental: Part B - efgartigimod PH20 SC PFS; Participants will receive efgartigimod PH20 SC Via Prefilled Syringe (PFS) during the part B treatment period.	Biological: Efgartigimod PH20 SC; Subcutaneous injection of Efgartigimod PH20 Via Prefilled Syringe (PFS)
Experimental: Part B - placebo PH20 SC PFS; Participants will receive placebo PH20 SC Via Prefilled Syringe (PFS) during the part B treatment period.	Other: Placebo PH20 SC; Subcutaneous injection of placebo PH20 via Prefilled Syringe (PFS)
Experimental: Part C - efgartigimod PH20 SC PFS; Participants will receive efgartigimod PH20 SC PFS in the part C open-label treatment period	Biological: Efgartigimod PH20 SC; Subcutaneous injection of Efgartigimod PH20 Via Prefilled Syringe (PFS)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Up to 24 weeks (part A)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to becoming euthyroid off ATDs in part A	ATDs: antithyroid drugs	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.	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.	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.	Up to 24 weeks (part A)
Time to becoming euthyroid off ATDs and TRAb seronegative	ATDs: antithyroid drugs; TRAb: anti-TSHR autoantibodies.	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.	Up to 24 weeks (Part A)
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)	TSH: thyroid-stimulating hormone; LLN: lower limit of normal.	Up to 24 weeks (part A)
Percentage of participants who remain euthyroid without ATDs	ATDs: antithyroid drug	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	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	Up to 72 weeks (part C)
Incidence of AEs and SAEs	AEs: adverse events ; SAEs: serious adverse events.	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.	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.	Up to 135 weeks
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	IgG: immunoglobulin G	Up to 98 weeks
Percentage change from baseline in TRAb serum levels over time	TRAb: anti-TSHR autoantibodies.	Up to 135 weeks
Incidence of ADA against efgartigimod in serum	ADA: antidrug antibody(ies)	Up to 24 weeks (part A) + up to 135 weeks
Incidence of antibodies against rHuPH20 in plasma	rHuPH20: recombinant human hyaluronidase PH20	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.	Up to 24 weeks (part A) + up to 135 weeks

Collaborators and Investigators

• Sponsor: argenx

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): May 1, 2030

Study Registration Dates

• First Submitted: April 30, 2026
• First Submitted That Met QC Criteria: April 30, 2026
• First Posted (Actual): May 6, 2026

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: April 30, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Eye Diseases; Exophthalmos; Orbital Diseases; Goiter; Hyperthyroidism; Thyroid Diseases; Graves Disease
• Other Study ID Numbers: ARGX-113-25-GRD-3002; 2025-524223-42-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No