This is a Phase 2, double-blind, placebo controlled, Methimazole (MMI) withdrawal study in subjects with Graves' disease. The study consists of up to 5 periods: a screening period of up to 2 weeks; a WP1302 or placebo titration with Methimazole period of 12 weeks; a Full dose of WP1302 or placebo with Methimazole tapering period of 26 weeks; a follow-up period of 4 weeks; and an extended follow-up period of 6 months. After screening, eligible subjects will be randomized to treatment at a ratio (stratified by size of goiter \[grade 0 or 1; grade 2\], WHO classification) of 1:1:1:1 to either any group of Methimazole with WP1302 at a dose of 400 μg, 800 μg, or 1200 μg, or the group of Methimazole with placebo. All the subjects will subsequently be enrolled in an extended safety follow-up period for an additional 6 months. Subjects who remain euthyroid will continue to be monitored for efficacy during the long-term follow-up.
This is a Phase 2, double-blind, placebo controlled, Methimazole (MMI) withdrawal study in subjects with Graves' disease. The study consists of up to 5 periods: a screening period of up to 2 weeks; a WP1302 or placebo titration with Methimazole period of 12 weeks; a full dose of WP1302 or placebo with Methimazole tapering period of 26 weeks; a follow-up period of 4 weeks; and an extended follow-up period of 6 months. After screening, eligible subjects will be randomized to treatment at a ratio (stratified by size of goiter \[grade 0 or 1; grade 2\], WHO classification) of 1:1:1:1 to either any group of Methimazole with WP1302 at a dose of 400 μg, 800 μg, or 1200 μg, or the group of Methimazole with placebo. Subjects who have a confirmed diagnosis of Graves' disease based on medical history and/or physical examination and laboratory evidence, well controlled, with normalized thyroid function tests, and have received stable background Methimazole (i.e., not requiring dose adjustments) not exceeding 20 mg daily for at least 8 weeks and no more than 24 weeks are eligible to this study. All subjects enrolled in this study will receive Methimazole treatment in titration period. During the titration period, subjects will receive WP1302 or placebo by subcutaneous (S.C.) injection every 2 weeks (Q2W) for 12 weeks while continuing MMI (see "Dosing" below). The dose of WP1302 will be titrated up to the target dose assigned to the subject during this period (see "Dosing" below). Thyroid symptoms and function tests will be evaluated every 2 weeks. The investigator may adjust the frequency of thyroid function tests based on safety considerations. If a subject does not maintain euthyroidism, which is defined as total T3 60-180 ng/dL, free T4 0.8-1.8 ng/dL, and TSH 0.5-5 mU/L, during the "WP1302 titration period", the subject will be discontinued from Investigational Medicinal Product (IMP) (i.e., WP1302 or placebo) and the subject is still required to complete the end-of study visit. During the 26-week full dose of WP1302 with Methimazole tapering period, subjects who have maintained euthyroidism during the "WP1302 titration period" will be dosed with WP1302 at 400, 800, or 1200 μg with down-titrated Methimazole. Thyroid symptoms and function tests will be evaluated every 2 weeks. The investigator may adjust the frequency of thyroid function tests based on safety considerations. Subjects who experience disease relapse will be treated with Methimazole as first-line therapy (see "Management of Relapse and Rescue Medication" below). At the end of the full dose of WP1302 with Methimazole tapering period, subjects will have 4 weeks of follow-up, and complete an end-of-study visit at Week 42. All the subjects will subsequently be enrolled in an extended safety follow-up period for an additional 6 months. Subjects who remain euthyroid will continue to be monitored for efficacy during the long-term follow-up.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
176
Each arm will be treated with methimazole. During the MMI tapering period, commences the MMI weaning by reducing the original dosage by 50%. This adjusted dose is to be administered over a two-week duration. Continue this dose reduction in the subsequent 2-week durations until achieving a dose of 2.5 mg/day or lower. Upon reaching this threshold, MMI is to be discontinued (withdrawal).
Each arm will be treated with methimazole. During the MMI tapering period, commences the MMI weaning by reducing the original dosage by 50%. This adjusted dose is to be administered over a two-week duration. Continue this dose reduction in the subsequent 2-week durations until achieving a dose of 2.5 mg/day or lower. Upon reaching this threshold, MMI is to be discontinued (withdrawal).
Each arm will be treated with methimazole. During the MMI tapering period, commences the MMI weaning by reducing the original dosage by 50%. This adjusted dose is to be administered over a two-week duration. Continue this dose reduction in the subsequent 2-week durations until achieving a dose of 2.5 mg/day or lower. Upon reaching this threshold, MMI is to be discontinued (withdrawal).
East Valley Diabetes and Endocrinology-Clinical Research, PLLC
Hunt, Arizona, United States
Alliance Research Institute
Canoga Park, California, United States
Paradigm Clinical Research Centers - Littleton
Littleton, Colorado, United States
BayCare Health System, Inc.
Clearwater, Florida, United States
Albuquerque Clinical Trials Inc
Albuquerque, New Mexico, United States
Cleveland Clinic
Cleveland, Ohio, United States
Clinical Research Solution LLC dba Endocrine and Psychiatry Center
Houston, Texas, United States
Relapse rate
To assess the relapse rate between the WP1302 and placebo treatment groups in subjects who enter the tapering phase
Time frame: Up to 42 weeks
Replase time
To assess the time duration from start of methimazole (MMI) tapering to disease relapse between the subjects treated with WP1302 and placebo.
Time frame: Up to 42 weeks
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
To assess the safety and tolerability of WP1302 administered with or without methimazole (MMI) in subjects with Graves' disease
Time frame: Up to 68 weeks including LTFU
Total T3, free T4, and TSH levels
To assess the effect of WP1302 on thyroid function (measured by total T3, free T4, and TSH levels)
Time frame: Up to 68 weeks including LTFU
Pharmacokinetics (PK) parameters (AUC, Cmax)
To assess the pharmacokinetics (PK) parameters (AUC, Cmax) of WP1302 in plasma
Time frame: Week 0 and Week 10
Incidence of anti-drug antibodies (ADAs)
To assess the incidence of anti-drug antibodies (ADAs) against WP1302
Time frame: Up to 68 weeks including LTFU
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.