Study to Evaluate the Dose, Safety and Effectiveness of Modified-Release Recombinant Human Thyroid Stimulating Hormone (MRrhTSH) When Used in Conjunction With Radioiodine for the Treatment of Multinodular Goiter.

Genzyme, a Sanofi Company0 sites96 target enrollmentJuly 2007

ConditionsMultinodular Goiter

InterventionsPlacebo MRrhTSH

DrugsMRrhTSH

Overview

Phase: Phase 2
Intervention: Placebo
Conditions: Multinodular Goiter
Sponsor: Genzyme, a Sanofi Company
Enrollment: 96
Primary Endpoint: Change from baseline to 6 months in goiter size by computer tomography (CT) scan.
Status: Completed
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief Summary

The purpose of this study is to determine the safety and effectiveness of 2 different doses of modified-release recombinant human thyroid stimulating hormone (MRrhTSH) when administered with radioiodine in patients with multinodular goiter, a condition that involves the enlargement of the thyroid gland. We will also evaluate the safety and effectiveness of radioiodine therapy alone in these patients. The goal of the treatment is to determine if there was a reduction in the size of the goiter and to study if goiter symptoms have improved after 6 months and after 36 months.

Registry

clinicaltrials.gov

Start Date

July 2007

End Date

July 2011

Last Updated

3 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Genzyme, a Sanofi Company

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Clinical diagnosis of multinodular goiter, judged clinically and by ultrasound at Screening to be at least 40 mL, but less than or equal to 140 mL in size.
•Clinically free of thyroid cancer as determined by Fine Needle Aspiration (FNA) of all dominant and/or highly suspicious cold nodules in the goiter and cytology reports as negative for thyroid cancer. (Note: Results of FNA and cytology reports that were performed within 18 months prior to commencing Screening procedures and meet these criteria are acceptable for inclusion).
•Principal Investigator must believe that there is a minimal risk of coexistent thyroid cancer.
•Principal Investigator feels that the patient's iodine intake and/or levels will not significantly impact the results of the study (urinary iodine assay at Screening and low-iodine diet are optional and associated data will not be collected for study purposes).
•Baseline serum level of free thyroxine index (FTI) within the normal range, as determined by central lab.
•Baseline serum level of thyroid stimulating hormone (TSH) ranges from undetectable to the upper limit of the normal range, as determined by central lab.
•Females of child-bearing potential must be on a stable hormonal contraceptive regimen (i.e., \> 6 months continuous use) and/or use a double barrier method (i.e., condom and foam) through Visit 8 (i.e. the end of the Core Study).
•Through Visit 8 (6 months) of a male patient's participation in the study, it is recommended that his sexual partner(s), who are females of child-bearing potential, use the above described methods of contraception.
•Negative pregnancy tests for all women of child-bearing potential prior to participating in the study. Women aged 50 years and above and considered postmenopausal (defined as \> 2 years since last menstrual period) will not need to have a pregnancy test.
•Routine blood laboratory values within normal range at Screening, as determined by central lab. Abnormal values considered to be not clinically significant by the Principal Investigator are acceptable for inclusion.

Exclusion Criteria

•History of thyroid cancer.
•Previous partial or near total thyroidectomy.
•Clinical history, signs or symptoms that make thyroid cancer a higher than usual probability, such as positive immediate family history of thyroid cancer, history of head or neck irradiation, a stone-hard nodule or suspicious growth of a nodule in recent months, palpable cervical lymph nodes or nodes that on ultrasound have features suspicious for metastases (unless ruled out by biopsy or FNA).
•During the 45 days before administration of MRrhTSH or placebo (i.e., Screening Periods 1 and 2), use of propylthiouracil, methimazole or thyroxine, vitamins or supplements containing kelp or iodine (taking a multivitamin that does not contain iodine or kelp is acceptable), medications that significantly affect iodine handling such as high dose corticosteroids, high dose diuretics, or lithium (low or moderate dose diuretic use is acceptable).
•Patient has currently or within the past 60 days used retinoic acid.
•Serum calcitonin above the upper limit of normal at Screening, as determined by central lab.
•Use of amiodarone within the prior 2 years.
•Received iodine-containing contrast agent within the past 3 months.
•Inability to complete all required visits.
•Patients with conditions in which use of beta-blockers are medically contraindicated, such as recently active asthma or clinically significant chronic obstructive pulmonary disease.

Arms & Interventions

Placebo

Intervention: Placebo

0.01 mg MRrhTSH + 131-I arm

Intervention: MRrhTSH

0.03 mg MRrhTSH + 131-I arm

Intervention: MRrhTSH

Outcomes

Primary Outcomes

Change from baseline to 6 months in goiter size by computer tomography (CT) scan.

Time Frame: Duration of core study

Extension Phase: Change in goiter size by CT scan at 36 months versus baseline, Months 6, 12 and 24

Time Frame: Duration of extension phase

Secondary Outcomes

Extension Phase: Change in goiter size from baseline to 6, 12, 24 and 36 months by SCAT and neck ultrasound.(Duration of extension phase)
Thyroid Stimulating Hormone (TSH), free thyroxine (FT4), total thyroxine (TT4), FT1, free triiodothyronine (FT3), total T3 (TT3).(Core Study and Extension Phase)
Physical Exams, Vitals, Adverse Events, Respiratory symptoms(Core Study and Extension Phase)
Routine labs, serial thyroid function tests, antibodies to MRrhTSH, antibodies against the thyroid stimulating hormone receptor, and physical exam.(Core study and extension phase)
Treatment-emergent hyperthyroidism (Hyperthyroid Symptom Scale (HSS) score ≥ 20).(Core study)
Change in goiter size from baseline to 6 months in smallest cross sectional area of the trachea (SCAT).(Duration of core study)
Thyroid Quality of Life Questionnaire(Core Study and Extension Phase)
The percentage of patients in each group who attained a goiter volume shrinkage at 6 months of 28% or greater.(Core Study)
Tracheal diameter measurements determined by ultrasound at Visit 3 compared to baseline measurement.(core study - Visit 3)
Electrocardiogram (ECG)(Duration of core study)