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

Primary Purpose

Graves' Disease

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

CFZ533

About this trial

This is an interventional treatment trial for Graves' Disease focused on measuring Graves' disease, Hyperthyroidism, CFZ533, TSH

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CFZ533 10mg/kg

Arm Description

CFZ533 intravenously over approximately one hour

Outcomes

Primary Outcome Measures

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)

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

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)

Secondary Outcome Measures

Full Information

NCT ID

NCT02713256

First Posted

March 15, 2016

Last Updated

December 9, 2020

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT02713256

Brief Title

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

2. Study Status

Record Verification Date

March 2019

Overall Recruitment Status

Completed

Study Start Date

April 19, 2016 (Actual)

Primary Completion Date

April 24, 2017 (Actual)

Study Completion Date

April 24, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Graves' Disease

Keywords

Graves' disease, Hyperthyroidism, CFZ533, TSH

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

15 (Actual)

8. Arms, Groups, and Interventions

Arm Title

CFZ533 10mg/kg

Arm Type

Experimental

Arm Description

CFZ533 intravenously over approximately one hour

Intervention Type

Drug

Intervention Name(s)

CFZ533

Intervention Description

CFZ533 intravenously over approximately one hour

Primary Outcome Measure Information:

Title

Percentage of Participants Whose Thyroid Stimulating Hormone (TSH) Levels Normalize After 12 Week Treatment

Description

Normalization of TSH is defined as TSH level greater than 0.35 mU/L after 12 week treatment (Day 85)

Time Frame

12 week (DAY 85)

Title

Percentage of Participants Whose Total Triiodothyronine (Total T3) Levels Decrease After 12 Week Treatment

Description

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

Time Frame

12 week (DAY 85)

Title

Percentage of Participants Whose Free Thyroxine (Free T4) Levels Decrease After 12 Week Treatment

Description

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)

Time Frame

12 week (DAY 85)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Novartis Investigative Site

City

Honolulu

State/Province

Hawaii

ZIP/Postal Code

96814

Country

United States

Facility Name

Novartis Investigative Site

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

Facility Name

Novartis Investigative Site

City

Mainz

ZIP/Postal Code

55131

Country

Germany

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Citations:

PubMed Identifier

34149627

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.

Results Reference

derived

PubMed Identifier

31512728

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.

Results Reference

derived

Links:

URL

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=228

Description

A Plain Language Trial Summary is available on novartisclinicaltrials.com

Learn more about this trial

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

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