A Study to Evaluate the Safety and Effect of CFZ533 on Patients With Graves' Disease

Study Overview
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Brief Summary
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An open label study to evaluate the safety and efficacy of CFZ533 following 12 weeks treatment in patients with Graves' disease

Official Title
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An Open Label Study to Evaluate the Safety and Efficacy of 12 Week Treatment With CFZ533 in Patients With Graves' Disease

Conditions
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Graves' Disease

Intervention / Treatment
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* Drug: CFZ533


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male and female patients 18 to 65 years of age included. Women of child-bearing potential must be willing to use highly effective methods of contraception during the study treatment epoch and for 12 weeks after the last study treatment. Graves' hyperthyroidism, with the following labs measured at screening: TSH<LLN and either FT3>ULN or FT4> ULN and TRAb ≥ 2.5 IU/L Patients must weigh at least 40 kg to participate in the study Key Exclusion Criteria: History of treatment of Graves' disease with radio-iodine ablation or thyroidectomy and/or current treatment with anti-thyroid drugs (methimazole or propylthiouracil) within one week of starting the study treatment History of hyperthyroidism not caused by Graves' disease (e.g. toxic multinodular goiter, autonomous thyroid nodule, or acute inflammatory thyroiditis) and/or history or presence of thyroid storm (fever, profuse sweating, vomiting, diarrhea, delirium, severe weakness, seizures, markedly irregular heartbeat, yellow skin and eyes (jaundice), severe low blood pressure, and coma). Previous treatment with a B cell-depleting biologic agent or any other immune-modulatory biologic agent within 5 half-lives (experimental or approved). History of recurrent clinically significant infection or of recurrent bacterial infections with encapsulated organisms. History of primary or secondary immunodeficiency, including a positive HIV (ELISA and Western blot) test result. History or evidence of tuberculosis by either of the following tests: Positive PPD skin test (size of induration measured after 48-72 hours, and a positive result is defined as an induration of ≥ 5mm or according to local practice/guidelines) OR Positive QuantiFERON TB-Gold test Plans for immunization with a live vaccine within a 2-month period before enrollment or during the study period. Treatment with immunomodulatory drugs, such as cyclosporine A, methotrexate, and/or cyclophosphamide within 3 months from baseline. Glucocorticosteroid therapy with prednisolone up to 10 mg daily is permitted if patients are on stable dose for more than 3 months before enrollment in the study. Pregnant, breastfeeding females, and women of child bearing potential unless they are using highly effective contraception

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CFZ533 10mg/kg<br>CFZ533 intravenously over approximately one hour | Drug: CFZ533<br>* CFZ533 intravenously over approximately one hour<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Whose Thyroid Stimulating Hormone (TSH) Levels Normalize After 12 Week Treatment | Normalization of TSH is defined as TSH level greater than 0.35 mU/L after 12 week treatment (Day 85) | 12 week (DAY 85) | 
| Percentage of Participants Whose Total Triiodothyronine (Total T3) Levels Decrease After 12 Week Treatment | Percentage of participants whose total triiodothyronine (total T3) levels decrease after 12 week treatment. A decrease is when total T3 level is below Upper limit of normal (ULN) ≤ 2.79 nmol/L | 12 week (DAY 85) | 
| Percentage of Participants Whose Free Thyroxine (Free T4) Levels Decrease After 12 Week Treatment | Percentage of participants whose free thyroxine (free T4) levels decrease after 12 weeks of treatment (DAY85). A decrease is when free T4 level is below Upper limit of normal (ULN) ≤ 22.7 pmol/L) | 12 week (DAY 85) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Graves' disease, Hyperthyroidism, CFZ533, TSH