E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Thyroid Eye Disease (TED) |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Eye Diseases [C11] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10057889 |
E.1.2 | Term | Graves' ophthalmopathy |
E.1.2 | System Organ Class | 100000004853 |
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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 primary objective is to evaluate the effect of teprotumumab on the roptosis responder rate (i.e., the percentage of subjects with a ≥ 2 mm reduction from Baseline in the study eye without deterioration [≥ 2 mm increase] of proptosis in the fellow eye) at Week 24. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives will evaluate the effect of teprotumumab on the
following:
1. Percentage of subjects with a Clinical Activity Score (CAS) value of 0 or 1 at Week 24 in the study eye.
2. Mean change from Baseline to Week 24 in proptosis measurement in the study eye.
3. Diplopia responder rate (i.e., the percentage of subjects with baseline diplopia > 0 in study eye who have a reduction of ≥ 1 grade with no corresponding deterioration [≥ 1 grade worsening] in the fellow eye) at Week 24.
4. Mean change from Baseline to Week 24 in the Graves'Ophthalmopathy Quality of Life (GO-QoL) questionnaire overall score. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent.
2. Completed the 24-week double-maskedTreatment Period in Study HZNP-TEP-301.
3. Proptosis non-responder (< 2 mm reduction in proptosis in the study eye) at Week 24 ofStudy HZNP-TEP-301 OR proptosis responder at Week 24 who relapses (see Section 9.3.4)during the Follow-Up Period of Study HZNP-TEP-301.
4. Subject must be euthyroid with the baseline disease under control, or have mild hypo- or hyperthyroidism (defined as free thyroxine [FT4] and free triiodothyronine [FT3] levels < 50% above or below the normal limits) at the most recent clinic visit.Every effort should be made to correct the mild hypo-or hyperthyroidism promptly and to maintain the euthyroid state for the full duration of the clinical trial.
5. Alanine aminotransferase (ALT) or aspartate aminotransferase(AST) ≤3 times the upper limit of normal (ULN) or serum creatinine <1.5 times the ULN (according to age) at the most recent clinic visit.
6. Diabetic subjects must have well-controlled disease (defined as HgbA1c < 9.0%at most recent clinic visit).
7. Does not require immediate surgical ophthalmological interventionand is not planning corrective surgery/irradiation during the course of the study.
8. Women of childbearing potentialmust have a negative urine pregnancy test at Baseline/Day 1. Subjects who are sexually active with a non-vasectomized male partner must agree to use 2 reliable forms of contraception during the trialand continue for 180 days after the last dose of study drug. One of the 2 forms of contraceptionis recommended to be hormonal, such as an oral contraceptive.Hormonal contraception must be in use for at least one full cycle prior to Baseline. Highly effective contraceptive methods (with a failure rate less than 1% per year), when used consistently and correctly, includes implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomized partner.
9. Male subjects must be surgically sterile or, if sexually active with a female partner of childbearing potential, must agree to use a barrier contraceptive method
from Baseline through 180 days after the last dose of study drug.
10. Subject is willing and able to comply with the prescribed treatment
protocol and evaluations for the duration of the study.
11. Has not received any treatment for TED since Week 24 of the HZNPTEP-
301 study. |
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E.4 | Principal exclusion criteria |
Subjects will be ineligible if, in the opinion of the Investigator, they are unlikely to comply with the study protocol or have a concomitant disease or condition that could interfere with the conduct of the study or potentially put the subject at unacceptable risk.
The exclusion criteria (except those related to screening) of protocol HZNP-TEP-301 also apply to this open-label extension study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure is the proptosis responder rate (percentage of subjects with a ≥ 2 mm reduction from Baseline in proptosis in the study eye, without deterioration [≥ 2 mm increase] of proptosis in the fellow eye) at Week 24. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Percentage of subjects with a CAS value of 0 or 1 in the study eye at Week 24.
2. Mean change from Baseline to Week 24 in proptosis measurement in the study eye.
3. Diplopia responder rate at Week 24
4. Mean change from Baseline to Week 24 in the GO-QoL questionnaire overall score. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
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 | No |
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 |
Germany |
Italy |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 8 |