Clinical trial NCT02713256: A Study to Evaluate the Safety and Effect of CFZ533 on Patients With Graves' Disease
Official title: An Open Label Study to Evaluate the Safety and Efficacy of 12 Week Treatment With CFZ533 in Patients With Graves' Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Graves' Disease
Keywords: Graves' disease
Hyperthyroidism
CFZ533
TSH
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-03-18
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants Whose Thyroid Stimulating Hormone (TSH) Levels Normalize After 12 Week Treatment
timeFrame: 12 week (DAY 85)
measure: Percentage of Participants Whose Total Triiodothyronine (Total T3) Levels Decrease After 12 Week Treatment
timeFrame: 12 week (DAY 85)
measure: Percentage of Participants Whose Free Thyroxine (Free T4) Levels Decrease After 12 Week Treatment
timeFrame: 12 week (DAY 85)
Secondary outcomes:
Other outcomes:
Locations:
city: Honolulu
country: United States
facility: Novartis Investigative Site
state: Hawaii
city: Rochester
country: United States
facility: Novartis Investigative Site
state: Minnesota
city: Mainz
country: Germany
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Faustino LC, Kahaly GJ, Frommer L, Concepcion E, Stefan-Lifshitz M, Tomer Y. Precision Medicine in Graves' Disease: CD40 Gene Variants Predict Clinical Response to an Anti-CD40 Monoclonal Antibody. Front Endocrinol (Lausanne). 2021 Jun 4;12:691781. doi: 10.3389/fendo.2021.691781. eCollection 2021.
citation: Kahaly GJ, Stan MN, Frommer L, Gergely P, Colin L, Amer A, Schuhmann I, Espie P, Rush JS, Basson C, He Y. A Novel Anti-CD40 Monoclonal Antibody, Iscalimab, for Control of Graves Hyperthyroidism-A Proof-of-Concept Trial. J Clin Endocrinol Metab. 2020 Mar 1;105(3):dgz013. doi: 10.1210/clinem/dgz013.