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

NCT02713256 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: CCFZ533X22052015-005564-41
• Study Type: interventional
• Target: 15
• Locations: 2 countries
• Sites: 3

Brief Summary

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

Conditions

Graves' Disease

Keywords

Graves' disease; Hyperthyroidism; CFZ533; TSH

Outcome Measures

Primary Outcomes (3)

• 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)

Study Arms (1)

CFZ533 10mg/kg

EXPERIMENTAL

CFZ533 intravenously over approximately one hour

Drug: CFZ533

Interventions

CFZ533 DRUG

CFZ533 intravenously over approximately one hour

CFZ533 10mg/kg

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (3)

Novartis Investigative Site

Honolulu, Hawaii, 96814, United States

Location

Novartis Investigative Site

Rochester, Minnesota, 55905, United States

Location

Novartis Investigative Site

Mainz, 55131, Germany

Location

Related Publications (2)

• 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.

  PMID: 34149627 DERIVED

• 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.

  PMID: 31512728 DERIVED

Related Links

• A Plain Language Trial Summary is available on novartisclinicaltrials.com

MeSH Terms

Conditions

Graves Disease; Hyperthyroidism

Interventions

iscalimab

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

8627788300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2016
• First Posted: March 18, 2016
• Study Start: April 19, 2016
• Primary Completion: April 24, 2017
• Study Completion: April 24, 2017
• Last Updated: January 5, 2021
• Results First Posted: May 21, 2018

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will share

Locations

DE (1); US (2)