Phase 2 Study to Assess Efficacy & Safety of WP1302 Prevent Relapse of MMI w/Draw in Subj. w/ Graves' dz

Trial details

Who runs it

Worg Biotherapeutics Inc.

Trial code

NCT06240455

Record updated

8 May 2025

Original description

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.Read full original descriptionShow less

A Double-blind, Placebo-controlled, Phase 2 Dose-range Study to Assess the Efficacy and Safety of WP1302 in Preventing Disease Relapse Following Methimazole Withdrawal in Subjects With Graves' Disease

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.

Inclusion: Age 18 to 65 years at the time of informed consent; Confirmed diagnosis of Graves' disease through medical history and/or physical examination, laboratory evidence as documented by a serum TSH\<0.5 mU/L and either a serum total T3 \>180 ng/dL or a serum free T4 \> 1.8 ng/dL; Current use of MMI at stable dose not exceeding 20 mg daily for at least 8 weeks and no more than 24 weeks by the baseline (Week 0); 60 ng/dL \< serum total T3 ≤ 180 ng/dL, 0.8 ng/dL \< serum free T4 ≤1.8 ng/dL, and 0.5 mU/L ≤ serum TSH \<5 mU/L at the Screening Visit; Willing and able to give written informed consent, agree to provide contact with the endocrinologist (or other appropriate trained healthcare provider), and to comply with protocol assessments/procedures; Male subjects must be sterile (biologically or surgically) or commit to the use of a reliable method of birth control for the duration of the study, and until at least 6 months after the last dose of WP1302; Female subjects of child-bearing potential must use a highly effective method of contraception throughout the entire duration of the study and for at least 6 months after the last dose of WP1302.

Exclusion: Currently using biotin supplements; Previous treatment with radioiodine or (partial or complete) thyroidectomy; Treatment with steroids (administered via the oral and/or parenteral routes) within 3 months prior to baseline or requiring intermittent use of systemic steroids for disease management (such as severe asthma), inhaled steroids are not prohibited; Prior treatment with immunotherapies (including rituximab), any cytokine or anti-cytokine therapy; Prior treatment with immunomodulatory drugs, such as cyclosporine A, methotrexate, and/or cyclophosphamide; Prior use of disease-related T cell-inducing therapy or peptide-tolerizing agent to treat Graves' disease; Receiving hemodialysis or peritoneal dialysis or microdialysis or continuous venovenous hemofiltration or continuous venovenous hemodialysis; Major surgery within 6 months prior to the screening visit or requiring ongoing active treatment after surgery irrespective of the time since surgery; Any vaccination within 30 days prior to screening, except for influenza and coronavirus vaccines; Participating in any clinical study of any investigational medication (i.e., unauthorized medication) within 90 days prior to randomization; Any other significant medical illness or psychiatric conditions that in the opinion of the investigator, would preclude participation in the study or impair the ability to give informed consent; any other clinically apparent autoimmune disease currently requiring disease-modifying or anti-inflammatory treatment; or significant illness which has not resolved within 4 weeks prior to the planned date of first dose of WP1302; Any other conditions or prior therapies, which, in the opinion of the investigator, would make the subject unsuitable for this study; Known history of allergy to the ingredients of WP1302, or hypersensitivity reaction that in the opinion of the investigator would exclude the subject's participation in the study; Subjects with known pituitary disease, such as traumatic brain disease, hyperprolactinemia, and hypophysitis; History of hyperthyroidism not caused by Graves' disease (e.g., toxic multinodular goiter, autonomous thyroid nodule, or acute inflammatory thyroiditis); Symptoms and signs of thyroid storm such as fever, profuse sweating, vomiting, diarrhea, delirium, severe weakness, seizures, markedly irregular heartbeat, yellow skin and eyes (jaundice), severe low blood pressure, and coma, pyrexia with no other cause than hyperthyroidism; Subjects who have a history of intolerance or contraindication to the use of beta-blockers; Subjects with history of arrhythmia, or cardiovascular accident, or other cardiovascular disease who maybe at increased risk of cardiac adverse events from treatment or recurrence of hyperthyroidism; Subjects with history of cerebrovascular accident/transient ischemic attack, or other cerebrovascular disease who maybe at increased risk of neurologic adverse events from treatment or recurrence of hyperthyroidism; History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases; Known history of active or chronic infectious disease or any disease which compromises immune function (e.g., HIV+, HTLV-1, active Lyme disease, latent or active TB, viral hepatitis); Active thyroid eye disease (clinical activity score [CAS] ≥3) with functional visual impairment sufficient to cause poor quality of life, or dysthyroid optic neuropathy likely to require immunosuppressive treatment during the 30 weeks of the study; Inadequate liver function, defined by a total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) or alkaline phosphatase \> 3 times the upper limits of the normal (ULN) at screening; Estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73m2, calculated as individual eGFR derived from Modification of Diet in Renal Disease formula; Documented presence of immunodeficiency or an immunocompromised condition including hematologic malignancy, bone marrow transplant, or known human immunodeficiency virus infection with a CD4 count \<200/mm3; Subjects who may have thyroid nodules that require alternative intervention; Being pregnant, breastfeeding, or planning to become pregnant during the study; Currently actively moderate-heavy using tobacco (≥10 cigarettes a day).

ClinicalTrials.gov NCT06240455