E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Preeclampsia |
Pre-eclampsie |
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E.1.1.1 | Medical condition in easily understood language |
Preeclampsia |
Zwangerschapsvergiftiging |
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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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary:
To evaluate the tolerability and safety of the treatment with rhC1INH on top of Standard Care, for patients with preeclampsia.
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primair:
Het evalueren van de tolerantie en veiligheid van de behandeling met rhC1INH samen met standaard behandeling voor patienten met pre-eclampsie |
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E.2.2 | Secondary objectives of the trial |
Secondary:
To evaluate the efficacy of treatment with rhC1INH on top of Standard Care, for patients with preeclampsia. |
Secundair:
Het evalueren van de effectiviteit van de behandeling met rhC1INH samen met standaard behandeling voor patienten met pre-eclampsie |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Pregnant females, aged ≥ 18 years
2. Singleton pregnancy
3. Between 25 and 35 weeks of gestation
4. Diagnosis of pre-eclampsia defined as hypertension developing after 20 weeks gestation and the coexistence of one or more of the following new onset conditions:
a. Proteinuria (spot urine protein/creatinine ≥30 mg/mmol [0.3 mg/mg] or ≥300 mg/day or at least 1 g/l [‘2+’] on dipstick testing)
b. Other maternal organ dysfunction:
- renal insufficiency (creatinine ≥90 Umol/l)
- liver involvement (elevated transaminases – at least twice upper limit of normal ± right upper quadrant or epigastric abdominal pain)
- neurological complications (examples include eclampsia, altered mental status, blindness, stroke, or more commonly hyperreflexia when accompanied by clonus, severe headaches when accompanied by hyperreflexia, persistent visual scotomata)
- hematological complications (thrombocytopenia – platelet count below 150,000/dL, DIC, hemolysis))
c. Uteroplacental dysfunction
- fetal growth restriction
5. Provided written informed consent.
6. Willingness and ability to comply with all protocol procedures.
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1. Zwangere vrouwen, leeftijd ≥ 18 jaar
2. Eenling zwangerschap
3. Tussen 25 en 35 weken zwangerschap
4. Diagnose van pre-eclampsie gedefinieerd als hypertensie die zich na 20 weken zwangerschap ontwikkelt met daarnaast de presentative van een van de volgende nieuwe aandoeningen die nog niet eerder aanwezig waren:
een. Proteïnurie (urineproteïne / creatinine ≥30 mg / mmol [0,3 mg / mg] of ≥300 mg / dag of minstens 1 g / l ['2+'] bij het testen van de urine)
b. Andere maternale orgaanstoornissen:
- nierinsufficiëntie (creatinine ≥90 Umol / l)
- gerelateerd aan de lever (verhoogde transaminasen - minstens tweemaal bovengrens van normaal ± rechtsbovenkwadrant of epigastrische buikpijn)
- neurologische complicaties (voorbeelden zijn eclampsie, veranderde mentale toestand, blindheid, beroerte, of vaker hyperreflexie wanneer dit gepaard gaat met clonus, ernstige hoofdpijn wanneer dit gepaard gaat met hyperreflexie, aanhoudende visuele scotomata)
- hematologische complicaties (trombocytopenie - aantal bloedplaatjes onder 150.000 / dL, DIC, hemolyse))
c. Uteroplacentale disfunctie
- foetale groeivermindering
5. Mits schriftelijke geïnformeerde toestemming.
6. Bereidheid en het vermogen om te voldoen aan alle protocolprocedures. |
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E.4 | Principal exclusion criteria |
1. Impending Fetal death compromise – absent end-diastolic umbilical artery flow, pathological CTG
2. Any known fetal abnormality
3. Patients diagnosed with hereditary angioedema (HAE)
4. Medical history of allergy to rabbits or rabbit-derived products (including rhC1INH)
5. Treatment with any investigational drug during the current pregnancy
6. Patient with known chronic hypertension requiring antihypertensive treatment
7. Patient with abnormalities in their clotting system.
8. Patient with known renal and/or hepatic abnormality
9. Patient with a history of malignancy (except if determined cured or on remission for at least 5 years)
10. Medical history of any organ transplants
11. Uncontrolled diabetes, defined as HbA1C > 7%
12. Currently treated with statins
13. Any other condition or treatment that, in the opinion of the Investigator, might interfere with the evaluation of study objectives
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1. Dreigend Foetale sterfte-compromis - afwezigheid van end-diastolische arteriële stroom, pathologisch CTG
2. Een bekende foetale afwijking
3. Patiënten met de diagnose erfelijk angio-oedeem (HAE)
4. Medische voorgeschiedenis van allergie voor konijnen of van konijnen afgeleide producten (inclusief rhC1INH)
5. Behandeling met een onderzoeksmedicijn tijdens de huidige zwangerschap
6. Patiënt bekend met chronische hypertensie waarvoor behandeling met bloedrukverlagers nodig is.
7. Patiënt met afwijkingen in hun stollingssysteem.
8. Patiënt met bekende nier- en / of leverafwijking
9. Patiënt met een historie van kwaadaardige tumoren(behalve indien genezen verklaard of in remissie gedurende ten minste 5 jaar)
10. Medische geschiedenis van transplantaties van organen
11. Ongecontroleerde diabetes, gedefinieerd als HbA1C> 7%
12. Momenteel behandeld met statines
13. Elke andere voorwaarde of behandeling die, naar de mening van de Onderzoeker, de evaluatie van de studiedoelstellingen zou kunnen verstoren |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Incidence and severity of adverse events
- Number and percentage of patients who discontinue study drug or withdraw from the study
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- Incidentie en ernst van bijwerkingen
- Aantal en percentage patiënten die de studiemedicatie staken of zich uit de studie terugtrekken |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Throughout the study |
Gedurende de studie |
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E.5.2 | Secondary end point(s) |
- Time from start of rhC1INH to day of delivery
- Proportion of patients reaching gestation week 37
|
- Tijd vanaf het begin van behandeling met rhC1INH tot de dag van geboorte
- Percentage patiënten dat de zwangerschaps week 37 bereikt |
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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 | No |
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) | 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.8.3 |
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 | No |
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 |
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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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Last subject last visit |
Laatste patient, laatste bezoek voor de studie |
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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 | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |