Graves' Disease
Conditions
Keywords
Graves' disease, Hyperthyroidism, CFZ533, TSH
Brief summary
An open label study to evaluate the safety and efficacy of CFZ533 following 12 weeks treatment in patients with Graves' disease
Interventions
DRUGCFZ533
CFZ533 intravenously over approximately one hour
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Whose Thyroid Stimulating Hormone (TSH) Levels Normalize After 12 Week Treatment | 12 week (DAY 85) | 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 | 12 week (DAY 85) | 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 | 12 week (DAY 85) | 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) |
Countries
Germany, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CFZ533 10 mg/kg CFZ533 intravenously over approximately one hour | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | CFZ533 10 mg/kg |
|---|---|
| Age, Continuous | 44.3 years STANDARD_DEVIATION 12.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 15 |
| other Total, other adverse events | 12 / 15 |
| serious Total, serious adverse events | 1 / 15 |
Outcome results
Primary
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)
Time frame: 12 week (DAY 85)
Population: Pharmacodynamic (PD) Analysis Set- all patients in the study was included in this analysis set. Patients who discontinue before 4 weeks of treatment for any reason are not counted for the calculation of responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CFZ533 10 mg/kg | Percentage of Participants Whose Free Thyroxine (Free T4) Levels Decrease After 12 Week Treatment | 30.8 percentage of participants |
Primary
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)
Time frame: 12 week (DAY 85)
Population: Pharmacodynamic (PD) Analysis Set- all patients in the study was included in this analysis set. Patients who discontinue before 4 weeks of treatment for any reason are not counted for the calculation of responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CFZ533 10 mg/kg | Percentage of Participants Whose Thyroid Stimulating Hormone (TSH) Levels Normalize After 12 Week Treatment | 0 percentage of participants |
Primary
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
Time frame: 12 week (DAY 85)
Population: Pharmacodynamic (PD) Analysis Set- all patients in the study was included in this analysis set. Patients who discontinue before 4 weeks of treatment for any reason are not counted for the calculation of responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CFZ533 10 mg/kg | Percentage of Participants Whose Total Triiodothyronine (Total T3) Levels Decrease After 12 Week Treatment | 38.5 percentage of participants |