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

NCT06240455 | Suspended Phase 2 DMC FDA Drug

• 1 other identifier: WP1302-CS-002
• Study Type: interventional
• Target: 176
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Graves Disease

Keywords

Graves' disease; preventing disease relapse; relapse rate; thyroid function

Outcome Measures

Primary Outcomes (1)

• Relapse rate

  To assess the relapse rate between the WP1302 and placebo treatment groups in subjects who enter the tapering phase

  Up to 42 weeks

Secondary Outcomes (5)

• Replase time

  Up to 42 weeks

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  Up to 68 weeks including LTFU

• Total T3, free T4, and TSH levels

  Up to 68 weeks including LTFU

• Pharmacokinetics (PK) parameters (AUC, Cmax)

  Week 0 and Week 10

• Incidence of anti-drug antibodies (ADAs)

  Up to 68 weeks including LTFU

Other Outcomes (4)

• Cytokine levels of IFN-γ, IL-2, IL-6, and IL-10

  Up to 42 weeks

• TSH receptor antibody (TRAb) levels

  Up to 68 weeks including LTFU

• HLA haplotypes

  Baseline

Study Arms (4)

WP1302 400μg

ACTIVE COMPARATOR

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 MMI with WP1302 at a dose of 400 μg, 800 μg, or 1200 μg, or the group of MMI with placebo. The study consists of up to 5 periods: a screening period of up to 2 weeks; a WP1302 or placebo titration with MMI period of 12 weeks; a Full dose of WP1302 or placebo with MMI tapering period of 26 weeks; a follow-up period of 4 weeks; and an extended follow-up period of 6 months.

Drug: WP1302; Combination Product: methimazole

WP1302 800μg

ACTIVE COMPARATOR

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 MMI with WP1302 at a dose of 400 μg, 800 μg, or 1200 μg, or the group of MMI with placebo. The study consists of up to 5 periods: a screening period of up to 2 weeks; a WP1302 or placebo titration with MMI period of 12 weeks; a Full dose of WP1302 or placebo with MMI tapering period of 26 weeks; a follow-up period of 4 weeks; and an extended follow-up period of 6 months.

Drug: WP1302; Combination Product: methimazole

WP1302 1200μg

ACTIVE COMPARATOR

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 MMI with WP1302 at a dose of 400 μg, 800 μg, or 1200 μg, or the group of MMI with placebo. The study consists of up to 5 periods: a screening period of up to 2 weeks; a WP1302 or placebo titration with MMI period of 12 weeks; a Full dose of WP1302 or placebo with MMI tapering period of 26 weeks; a follow-up period of 4 weeks; and an extended follow-up period of 6 months.

Drug: WP1302; Combination Product: methimazole

WP1302 Placebo

PLACEBO COMPARATOR

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 MMI with WP1302 at a dose of 400 μg, 800 μg, or 1200 μg, or the group of MMI with placebo. The study consists of up to 5 periods: a screening period of up to 2 weeks; a WP1302 or placebo titration with MMI period of 12 weeks; a Full dose of WP1302 or placebo with MMI tapering period of 26 weeks; a follow-up period of 4 weeks; and an extended follow-up period of 6 months.

Drug: WP1302 placebo; Combination Product: methimazole

Interventions

WP1302 DRUG

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).

WP1302 1200μg; WP1302 400μg; WP1302 800μg

WP1302 placebo DRUG

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).

WP1302 Placebo

methimazole COMBINATION_PRODUCT

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).

WP1302 1200μg; WP1302 400μg; WP1302 800μg; WP1302 Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.

You may not qualify if:

• Currently using biotin supplements.
• 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.
• Previous treatment with radioiodine or (partial or complete) thyroidectomy.
• Subjects with known pituitary disease, such as traumatic brain disease, hyperprolactinemia, and hypophysitis.
• 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.
• History of hyperthyroidism not caused by Graves' disease (e.g., toxic multinodular goiter, autonomous thyroid nodule, or acute inflammatory thyroiditis).
• Subjects who may have thyroid nodules that require alternative intervention.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• Worg Biotherapeutics Inc.: lead

Study Sites (7)

East Valley Diabetes and Endocrinology-Clinical Research, PLLC

Hunt, Arizona, 85143, United States

Location

Alliance Research Institute

Canoga Park, California, 22110, United States

Location

Paradigm Clinical Research Centers - Littleton

Littleton, Colorado, 80120, United States

Location

BayCare Health System, Inc.

Clearwater, Florida, 33759, United States

Location

Albuquerque Clinical Trials Inc

Albuquerque, New Mexico, 87102, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Clinical Research Solution LLC dba Endocrine and Psychiatry Center

Houston, Texas, 77095, United States

Location

MeSH Terms

Conditions

Graves Disease

Interventions

Methimazole

Condition Hierarchy (Ancestors)

Exophthalmos; Orbital Diseases; Eye Diseases; Goiter; Thyroid Diseases; Endocrine System Diseases; Hyperthyroidism; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Sulfhydryl Compounds; Sulfur Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Dylan Lee, MD

  Worg Biotherapeutics Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2024
• First Posted: February 5, 2024
• Study Start: March 31, 2026
• Primary Completion (Estimated): March 31, 2029
• Study Completion (Estimated): September 30, 2030
• Last Updated: May 8, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)