E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Neuromyelitis Optica and Neuromyelitis Optica Spectrum Disorders (NMO/NMOSD) |
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E.1.1.1 | Medical condition in easily understood language |
Neuromyelitis optica (NMO) and NMO Spectrum Disorders, involve inflammation and damage of the optic nerve (optic neuritis), spinal cord (myelitis) and certain areas of the brain. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029322 |
E.1.2 | Term | Neuromyelitis optica |
E.1.2 | System Organ Class | 100000004852 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the efficacy of MEDI-551 versus placebo in reducing the risk of an NMO/NMOSD attack |
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E.2.2 | Secondary objectives of the trial |
1. To compare the efficacy of MEDI-551 versus placebo on the reduction of EDSS worsening
2. To compare the efficacy of MEDI-551 versus placebo on the change from baseline of low-contrast visual acuity score
3. To compare the efficacy of MEDI-551 versus placebo in reducing the cumulative active MRI lesion count
4. To compare the efficacy of MEDI-551 versus placebo in reducing NMO/NMOSD-related in-patient hospitalizations
5. To characterize the long-term efficacy of MEDI-551 by means of annualized attack rate.
6. To evaluate the safety and tolerability of a single course of MEDI-551 in randomised control phase and repeated doses of MEDI-551 in open label phase
7. To characterize the pharmacokinetic (PK) profile and immunogenicity of MEDI-551 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Men and women 18 years or older with diagnosis of NMO/NMOSD.
2) Confirmation of NMO/NMOSD status:
a.) AQP4-IgG sero-positive NMO/NMOSD with at least one attack requiring rescue
therapy in the last year or two attacks requiring rescue therapy in the last 2 years.
b.) AQP4-IgG sero-negative NMO with at least one attack requiring rescue therapy in the
last year or two attacks requiring rescue therapy in the last 2 years.
3) Able and willing to give written informed consent and comply with the requirements of the study protocol.
4) EDSS <= 7.5 (8 in special circumstances).
5) Men and women of reproductive potential must agree to use a highly effective method of birth control from screening to 6 months after final dose of the investigational product. |
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E.4 | Principal exclusion criteria |
1) Lactating and pregnant females.
2) Treatment with any investigational agent within 4 weeks of screening.
3) Known history of a severe allergy or reaction to any component of the investigational product formulation or history of anaphylaxis following any biologic therapy.
4) Known active severe bacterial, viral, or other infection or any major episode of infection requiring hospitalization.
5) History of of alcohol, drug, or chemical abuse, or a recent history of such abuse < 1 year prior to randomization.
6) Receipt of the following at any time prior to randomization:
a) Alemtuzumab
b) Total lymphoid irradiation
c) Bone marrow transplant
d) T-cell vaccination therapy
7) Receipt of rituximab or any experimental B-cell depleting agent within 6 months prior screening and B-cells below the lower limit of normal.
8) Receipt of IVIG within 1 month prior to randomization.
9) Receipt of any of the following within 3 months prior to randomization:
a) Natalizumab (Tysabri®)
b) Cyclosporin
c) Methotrexate
d) Mitoxantrone
e) Cyclophosphamide
f) Tocilizumab
g) Eculizumab
10) History of Hepatitis B and/or Hepatitis C (Hep B/C at screening).
11) Known history of a primary immunodeficiency (congenital or acquired) or an underlying condition such as human immunodeficiency virus (HIV) infection.
12) History of malignancies, apart from squamous cell or basal cell carcinoma of the skin treated with documented success of curative therapy > 3 months prior to randomization.
13) Any concomitant disease other than NMO/NMOSD that required treatment with oral or intravenous steroids at doses over 20 mg a day for over 21 days. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to an NMO/NMOSD attack determined by Adjudication Committee in randomized-control period |
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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. Worsening from baseline in EDSS at last visit during the RCP.
2. Change from baseline in low-contrast visual acuity binocular score measured by low-contrast Landolt C Broken Rings Chart, at last visit during RCP.
3. Cumulative total active MRI lesions (new Gd-enhancing or new/enlarging T2) during the RCP.
4. Number of NMO/NMOSD-related in-patient hospitalizations. In-patient hospitalization is defined as more than an overnight stay.
5. Annualized attack rate (total number of AC-determined NMO/NMOSD attacks normalized by person years) during any exposure to MEDI-551.
6. Treatment-emergent adverse events (TEAEs), including treatment-emergent serious adverse events (TESAEs). Laboratory measurements as well as their changes or shift from baseline over time.
7. Pharmacokinetic profile of MEDI-551.
8. Incidence of anti-drug antibodies (ADAs) directed against MEDI-551 for the duration of the study, both predose and postdose for each subject. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
End of Randomized-controlled Period and End of Study |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
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) | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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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.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Information not present in EudraCT |
E.8.5.1 | Number of sites anticipated in the EEA | 62 |
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 |
Australia |
Bulgaria |
Canada |
Colombia |
Czech Republic |
Estonia |
Germany |
Greece |
Hong Kong |
Hungary |
Israel |
Japan |
Korea, Republic of |
Mexico |
Moldova, Republic of |
New Zealand |
Peru |
Poland |
Portugal |
Russian Federation |
Serbia |
South Africa |
Spain |
Taiwan |
Thailand |
Turkey |
Ukraine |
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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The end of the study is defined as the date of the last protocol-specified visit/assessment (including telephone contact) for the last subject in the study. This will occur when the last subject completes the 52-week safety follow up. |
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |