E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Nodular goiter are clinically recognizable enlargements of the thyroid gland characterized by excessive growth and structural and or functional transformation of one or several areas within the normal thyroid tissue. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10043808 |
E.1.2 | Term | Thyrotropin |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The objective of this study is to determine the dose-response and safety of 2 doses of MRrhTSH with radioiodine (131I) therapy to achieve goiter shrinkage and improve goiter symptoms compared with 131I therapy alone in an adult population with small to moderate-sized multinodular goiter.
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E.2.2 | Secondary objectives of the trial |
Reduction of goiter by 28% volume shrinkage. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Adults aged 40 – 80 years old, inclusive. 2.Clinical diagnosis of multinodular goiter, judged clinically and by ultrasound at Screening to be at least 40 mL, but less than or equal to 110 mL in size. 3.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 signing informed consent and meet these criteria are acceptable for inclusion).
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E.4 | Principal exclusion criteria |
1.History of thyroid cancer. 2.Previous partial or near total thyroidectomy. 3.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).
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint: •Change from baseline to 6 months in goiter size by recent-generation CT scan.
Secondary endpoints: •Change from baseline to 6 months in smallest cross-sectional area of the trachea (SCAT). •Change in 24 hour (h) and either 72 or 96 h radioiodine uptake from baseline to post-treatment. •Thyroid Quality of Life Questionnaire (ThyQoL). •TSH, free thyroxine (FT4), total thyroxine (T4), FTI, free T3, total T3. •The percentage of patients in each group that attained a goiter volume shrinkage at 6 months of 28% or greater.
Safety Endpoints: •Routine labs, serial thyroid function tests, EKG, medical history, and physical exam. •Thyroid ultrasound and tracheal diameter measurements after treatment compared to initial measurement. •EKG findings (12 lead, 2 minute rhythm strip) in all patients. •Tachyarrhythmia Assessment (Directed Questions). •Respiratory Symptoms (Directed Questions). •AEs / Serious adverse events (SAEs). •Vital signs. •Treatment-emergent hyperthyroidism (HSS score ≥ 20).
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 12 |