E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Paroxysmal nocturnal hemoglobinuria |
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E.1.1.1 | Medical condition in easily understood language |
Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by the destruction of red blood cells. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10055629 |
E.1.2 | Term | Paroxysmal nocturnal hemoglobinuria |
E.1.2 | System Organ Class | 100000004857 |
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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 |
The primary objective of the study is to demonstrate a reduction in intravascular hemolysis by REGN3918 over 26 weeks of treatment in patients with active PNH who are treatment naive to complement inhibitor therapy or have not recently received complement inhibitor therapy |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are: •To evaluate the safety and tolerability of REGN3918. •To evaluate the effect of REGN3918 on parameters of intravascular hemolysis •To assess the concentrations of total REGN3918 in serum. •To evaluate the incidence of treatment emergent anti drug antibodies to REGN3918. •To evaluate the effect of REGN3918 on patient reported outcomes (PROs) measuring fatigue and health related quality of life
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
There are optional future biomedical research and pharmacogenomic analysis sub-studies . Subjects will be required to sign separate sub-study ICFs before collection of samples. There is no separate protocol. The purpose of the genomic analyses is to identify genomic associations with clinical or biomarker response, other clinical outcome measures and possible AEs. In addition, associations between genomic variants and prognosis or progression of as well as other diseases may also be studied. In addition, PROs such as fatigue or quality of life in a subset of patients at participating sites will be assessed (ie, sub study). There will not be separate sub-study protocols. |
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E.3 | Principal inclusion criteria |
• Male or female ≥ 18 years of age or legal age of majority at screening, whichever is greater •Diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) confirmed by high sensitivity flow cytometry •Active disease, as defined by the presence of 1 or more PNH related signs or symptoms or history of red blood cell (RBC) transfusion due to PNH within 3 months of screening. •Lactate dehydrogenase (LDH) level ≥ 2 × upper limit of normal (ULN) at screening visit. • PNH granulocytes (denoted as polymorphonuclear [PMN]) >10% at screening visit.
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E.4 | Principal exclusion criteria |
•Prior treatment with a complement inhibitor either within 6 months prior to screening visit or at any time where the patient was refractory to complement inhibitor therapy, in the opinion of the investigator (with the exception of eculizumab refractory patients due to the C5 variant R885H/C) |
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E.5 End points |
E.5.1 | Primary end point(s) |
The co primary endpoints are: •The proportion of patients achieving adequate control of their intravascular hemolysis, defined as LDH ≤ 1.5 x ULN at every scheduled time point between week 4 and week 26, inclusive •The proportion of patients achieving transfusion avoidance defined as no post baseline transfusion of RBCs per protocol over 26 weeks |
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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) |
The secondary endpoints include: •The rate of breakthrough hemolysis over 26 weeks, defined as the measurement of LDH ≥ 2 x ULN concomitant with associated signs or symptoms at any time subsequent to an initial achievement of disease control (ie, LDH ≤ 1.5 x ULN) •The proportion of patients achieving normalization of their intravascular hemolysis, defined as LDH ≤ 1.0 x ULN at every scheduled time point between week 4 through week 26, inclusive •Time to first LDH ≤ 1.5 x ULN •Percentage of days with LDH ≤ 1.5 x ULN between week 4 and week 26, inclusive. •Change and percent change in LDH levels from baseline to week 26 |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
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 |
Canada |
Germany |
Hong Kong |
Hungary |
Italy |
Korea, Democratic People's Republic of |
Malaysia |
Netherlands |
Poland |
Romania |
Singapore |
South Africa |
Taiwan |
United Kingdom |
United States |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |