E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pre-eclampsia |
Pre-eclampsia |
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E.1.1.1 | Medical condition in easily understood language |
Pre-eclampsia (Pre-eclampsia is a combination of proteinuria and hypertension during pregnancy) |
Pre-eclampsia (la pre-eclampsia e' una combinazione di proteinuria e ipertensione durante la gravidanza) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036485 |
E.1.2 | Term | Pre-eclampsia |
E.1.2 | System Organ Class | 10036585 - Pregnancy, puerperium and perinatal conditions |
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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 |
Part 1: To assess the maternal, fetal, and neonatal safety and tolerability of RLX030 at three doses and placebo when administered intravenously as infusion for 72 hours to women with pre-eclampsia. To investigate the Pharmacokinetics (PK) and development of anti-drug antibodies (ADAs) (maternal/neonatal) after RLX030 and placebo when administered intravenously as infusion for 72 hours to women with preeclampsia. Part 2: To assess the efficacy of RLX030 at the selected dose from Part 1 vs. placebo when administered intravenously as infusion for 72 hours on prolonging pregnancy in days (24 hours) in women with pre-eclampsia. |
Parte 1:Valutare la sicurezza e la tollerabilita' materna, fetale e neonatale di RLX030 a tre dosi (15, 40 e 75 μg/kg/giorno) e di placebo somministrati per via endovenosa (e.v.) tramite infusione per 72 ore a donne con pre-eclampsia, valutando gli effetti: sull’emodinamica materna e fetale, compresa sulla pressione sistolica e diastolica, sulla pressione arteriosa media (materna), sul flusso sanguigno utero-placentare e sulla frequenza cardiaca fetale (fetal heart rate – FHR) sulla proteinuria e sulla funzionalita' renale materne sul tasso di parto spontaneo e/o sulle modalita' del parto sugli esiti avversi materni sulla cardiotocografia fetale e sul profilo biofisico sul peso alla nascita, sull’eta' gestazionale, sul punteggio APGAR, sui gas del cordone ombelicale e sui giorni di permanenza nell’Unita' di Terapia Intensiva Neonatale ..(PER FAVORE VED. SINOSSI IN ITALIANO) |
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E.2.2 | Secondary objectives of the trial |
Part 1: To assess the effects of RLX030 at three doses and placebo when administered intravenously as infusion for 72 hours on prolonging of pregnancy in days (24 hours) in women with pre-eclampsia. Part 2: To assess the effects of RLX030 versus placebo when administered intravenously as infusion for 72 hours in women with pre-eclampsia. To investigate the Pharmacokinetics (PK) ,and development of anti-drug antibodies (ADAs) (maternal/neonatal) after RLX030 and placebo when administered intravenously as infusion for 72 hours to women with pre eclampsia. |
Parte 1 : Valutare gli effetti di RLX030 a tre dosi (15,40 e 75 μg/kg/giorno) e di placebo somministrati per via endovenosa tramite infusione per 72 ore nel prolungare la gravidanza in giorni (24 ore) in donne con pre-eclampsia.Parte 2 Valutare gli effetti di RLX030 rispetto a placebo somministrati per via endovenosa tramite infusione per 72 ore in donne con pre-eclampsia: sull’emodinamica materna e fetale,compresa sulla pressione sistolica e diastolica,sulla pressione arteriosa media (materna),sul flusso sanguigno utero-placentare e sull’FHR sulla proteinuria e sulla funzionalita' renale materne sul tasso di parto spontaneo e/o sulle modalita' del parto sugli esiti avversi materni sulla cardiotocografia fetale e sul profilo biofisico sul peso alla nascita,sull’eta' gestazionale,sul punteggio APGAR..(PER FAVORE VEDERE SINOSSI IN ITALIANO) |
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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 |
PHARMACOGENETIC:
Vers:V01
Date:2011/12/01
Title:The study includes an optional pharmacogenetic component which requires a separate signature if the patient agrees to participate. It is required as part of this protocol that the Investigator presents these options to the patient.
Objectives:Exploratory pharmacogenetics research studies are planned as a part of this study with the objectives of identifying inherited genetic factors which may (1) be related to pre-eclampsia, (2) predict response to treatment with RLX030, (3) predict relative susceptibility to drug-drug interactions, or (4) predict genetic predisposition to side effects. We hope to develop a better understanding of pre-eclampsia and how subjects respond to RLX030.
PHARMACOGENOMIC:
Vers:V01
Date:2011/12/01
Title:Pharmacogenomics RNA expression profiling will be carried-out in enrolled patients who are willing to participate in this exploratory biomarker evaluation and give consent. It is required as part of this protocol that the Investigator presents these options to the subject.
Objectives:Exploratory pharmacogenomic assessments in this study will assess circulating plasma miRNA levels in an attempt to: i) increasing our understanding of the molecular heterogeneity of pre-eclampsia, ii) identifying circulating miRNAs modulated by RLX030, and iii) identifying miRNAs associated with response to treatment with RLX030. In brief, miRNA-based molecular patterns will be derived from plasma.
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FARMACOGENETICA:
Vers:V01
Data:2011/12/01
Titolo:Vi informiamo che, anche se il protocollo non prevede uno sottostudio formalmente definito (ovvero strutturato con un protocollo specifico) ma una indagine complementare opzionale, la stessa viene classificata come sottostudio e quindi formalizzata nell’apposita sezione del CTA Form.
Obiettivi:Indagine esplorativa sugli indicatori biologici (farmacogenetica e farmacogenomica)
FARMACOGENOMICA:
Vers:V01
Data:2011/12/01
Titolo:Vi informiamo che, anche se il protocollo non prevede uno sottostudio formalmente definito (ovvero strutturato con un protocollo specifico) ma una indagine complementare opzionale, la stessa viene classificata come sottostudio e quindi formalizzata nell’apposita sezione del CTA Form.
Obiettivi:Indagine esplorativa sugli indicatori biologici (farmacogenetica e farmacogenomica)
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E.3 | Principal inclusion criteria |
- Women that are 28- 33 weeks (+4 days) pregnant with a diagnosis of pre- eclampsia or superimposed pre-eclampsia requiring hospitalization - Fetus deemed in reasonably good health Other protocol-defined inclusion criteria may apply |
Donne di eta' compresa tra i 18 e i 40 anni e con una gravidanza ≥ 28 settimane (0 giorni) e ≤ 33 settimane (+4 giorni) di gestazione (l’eta' gestazionale si basa sulle ultime mestruazioni della madre) e diagnosi di pre-eclampsia o pre-eclampsia sovrapposta che necessita di ricovero ospedaliero. La pre-eclampsia e' definita come insorgenza di ipertensione (≥140/90 mmHg) o ipertensione gestazionale accompagnata da proteinuria (≥ 0.3 g/24h) dopo 20 settimane di gestazione. La pre-eclampsia sovrapposta e' definita come ipertensione cronica con nuova insorgenza di proteinuria dopo 20 settimane di gestazione. Esami fetali rassicuranti. |
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E.4 | Principal exclusion criteria |
- Severe hypertension and /or those receiving anti-hypertensive treatment at time of enrollment - Severe headaches, visual changes, or altered mentation - Upper abdominal pain, nausea, or vomiting - Low blood platelet count - Diagnosis of a seizure disorder that requires chronic medication - Those receiving active anti-coagulation therapy - Pre-gestational diabetes (Type 1 or Type 2) - Allergy to magnesium sulfate or steroids - Known major fetal anomaly - Multifetal gestation Other protocol-defined exclusion criteria may apply |
Ipertensione severa (SBP ≥160 mmHg, DBP ≥ 110 mmHg) e/o soggetti che ricevono un trattamento anti-ipertensivo al momento dell’arruolamento. Sintomi indicativi di pre-eclampsia severa o sindrome HELLP (anemia emolitica, aumento degli enzimi epatici e bassa conta piastrinica) per cui potrebbe essere indicato il parto immediato. I sintomi comprendono: sintomi persistenti a carico del SNC (cefalee severe, variazioni nella vista, alterazioni dell’attivita' mentale), dolore persistente al quadrante superiore destro o dolore epigastrico, nausea o vomito, trombocitopenia severa (<100,000/mm3) ed enzimi epatici (ALT o AST) anormali (>2x limite superiore di normalita' – ULN). Eclampsia durante l’attuale gravidanza. Diagnosi corrente di disordini convulsivi che richiedono trattamento cronico. Donne in trattamento con terapia anti-coagulante. Diabete pre-gestazionale (di Tipo 1 o di Tipo 2) e retinopatia diabetica. La diagnosi (pregressa o attuale) di diabete gestazionale, indipendentemente dal trattamento, non costituisce criterio di esclusione. Allergia nota al magnesio solfato o agli steroidi. Anomalia fetale maggiore nota. Restrizione della crescita intrauterina (< 5° percentile, fare riferimento all’Appendice 4 del protocollo). Per maggiori dettagli consultare i paragrafi 4.1 e 4.2 del protocollo originale. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Part 1: Safety and tolerability Part 2: Days to delivery Safety and tolerability will be assessed by adverse events, blood pressure and renal function of the mother, blood flow, heart rate, gestational age and health outcome of the fetus. Days of pregnancy will be calculated as the time between start of dosing and time of decision for delivery of birth in hours divided by 24. |
Parte 1: Sicurezza e tollerabilita' Parte 2: prolungamento della gravidanza (giorni al parto) Sicurezza e tollerabilita' saranno valutati dagli eventi avversi, dalla pressione sanguigna e dalla funzione renale della madre, del flusso sanguigno, della frequenza cardiaca, dell'eta' gestazionale e del risultato di salute del feto. I giorni della gravidanza saranno calcolati come il tempo fra l'inizio di dosaggio e periodo della decisione per la nascita in ore divise per 24. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Prior to delivery until 4-6 weeks post partum |
Prima del parto fino a 4-6 settimane post partum |
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E.5.2 | Secondary end point(s) |
1. Part 1: Days to delivery Part 2: Safety and tolerability Measure as for the primary end point above 2. Blood concentrations of RLX030 3. Blood samples for measurement of antibodies to RLX030 |
1. Parte 1: Giorni al parto Parte 2 : Sicurezza e tollerabilita' misurate come nell'end point primario 2. Concentrazione di RLX030 nel sangue 3. Campioni di sangue per la misura degli anticorpi a RLX030 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Prior to delivery until 4-6 weeks post partum 2. Baseline, 2, 6, 24, 48, 72, 76, 80 and 90 hours after initiation of infusion 3. Baseline and 7 days post-partum in both mother and infant |
1-Prima del parto fino a 4-6 settimane post partum 2. Baseline 2, 6, 24, 48, 72, 76, 80 e 90 ore dopo l'inizio dell'infusione 3. Baseline e 7 giorni post-partum in entrambi madre e neonato |
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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 | 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 | 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) | 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 | 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 | 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.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
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 |
South Africa |
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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End of trial is the last visit of the last subject in the trial planned 27/MAY/2014. |
La conclusione della sperimentazione e' l'ultima visita dell'ultimo soggetto (LVLS) prevista 27/05/2014 |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 24 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 24 |
E.8.9.2 | In all countries concerned by the trial days | 0 |