E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Atypical Hemolytic Uremic Syndrome |
Sindrome Emolitico Uremica atipica |
|
E.1.1.1 | Medical condition in easily understood language |
Atypical Hemolytic Uremic Syndrome |
Sindrome Emolitico Uremica atipica |
|
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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019515 |
E.1.2 | Term | Hemolytic uremic syndrome |
E.1.2 | System Organ Class | 100000004851 |
|
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 evaluate whether in vivo CCX168 treatment dampens the ex vivo prothrombogenic properties of serum from ten chronic dialysis patients with aHUS on cultured microvascular endothelial cells. |
Valutare, su cellule endoteliali del microcircolo in coltura, se il trattamento in vivo con CCX168 determina una diminuzione delle proprietà protrombogeniche del siero derivante da 10 pazienti affetti da SEU atipica in trattamento dialitico cronico. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the effects of in vivo CCX168 treatment on: i. Biomarkers of complement and disease activity ii. Clinical parameters including pre-dialysis and intradialytic blood pressure and heart rate iii. Safety and tolerability parameters iv. Patient health-related quality of life v. CCX168 pharmacokinetic (PK) profile. |
Valutare gli effetti in vivo del trattamento con CCX168 su: i. Biomarkers dell’attività del complemento e della malattia comprendenti: - Depositi ex vivo di C5b-9 sulle cellule endoteliali del microcircolo; - Livelli sierici di C3, C4 e C5; - Attività totale residua del complemento CH50; - CFH, SC5b-9, Bb, e C5a su plasma raccolto su EDTA; - Trombomodulina solubile, VCAM-1 sierico, TNF alfa, prodotti dello split della fibrina; - Livelli sierici di LDH, conta piastrinica, conta dei neutrofili, valori di emoglobina. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age >18 years; - Diagnosis of aHUS with or without identified genetic abnormalities in the complement system or thrombomodulin; - Stable chronic extracorporeal or peritoneal dialysis therapy since at least 6 months; - Written informed consent. |
- Età >18 anni; - Diagnosi di SEU atipica in presenza o in assenza di anomalie genetiche del sistema del complemento o della trombomodulina; - Trattamento dialitico extracorporeo o peritoneale cronico stabile da almeno 6 mesi; - Consenso informato scritto. |
|
E.4 | Principal exclusion criteria |
- Women of childbearing potential or women who are breastfeeding; - Shiga toxin-associated HUS or secondary forms of thrombotic microangiopathy; - ADAMTS13 activity <10 % or circulating anti ADAMTS13 autoantibodies consistent with the diagnosis of thrombotic thrombocytopenic purpura; - Need for specific intervention with plasma therapy and/or complement inhibitors as deemed clinically appropriate; - Plasma therapy or treatment with complement inhibitors or antiplatelet and antithrombotic agents over the last two weeks; - Liver function impairment (serum liver enzymes or bilirubin levels >3 x upper limit of normal); - Neutrophil count < 2000/μL or lymphocyte count < 1000/μL; - Infection requiring antibiotic treatment within the previous 4 weeks prior to screening; - Participated in any clinical study of an investigational product within 30 days prior to screening or within 5 half-lives after taking the last dose; - History or presence of any medical condition or disease which, in the opinion of the Investigator may place the subject at unacceptable risk for study participation; - Inability to understand the potential risks and benefits of the study; - Legal incapacity. |
- Donne potenzialmente fertili o in allattamento; - SEU Stx-associata o forme secondarie di microangiopatia trombotica; - Attività di ADAMTS13 <10 % o presenza di auto anticorpi circolanti anti ADAMTS13 consistente con la diagnosi di TTP; - Necessità di terapia plasmatica e/o terapia con inibitori del complemento; - Terapia plasmatica o trattamento con inibitori del complemento o agenti antipiastrinici e antitrombotici nelle due settimane precedenti; - Insufficienza epatica (enzimi epatici o livelli di bilirubina superiori di più di tre volte del valore di normalità superiore); - Numero di neutrofili < 2000/μL o numero di linfociti < 1000/μL; - Infezioni che abbiano richiesto il trattamento con antibiotici nelle 4 settimane precedenti lo screening; - Partecipazione ad uno studio clinico interventistico nei 30 giorni precedenti lo screening o nel periodo corrispondente a 5 emivite del farmaco a partire dall’ultima dose assunta; - Storia o presenza di qualsiasi condizione clinica o patologia che, a giudizio dello sperimentatore, esponga il paziente ad un rischio inaccettabile in caso di partecipazione allo studio; - Incapacità di comprendere i potenziali rischi e benefici dello studio; - Incapacità legale. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Ex vivo thrombogenesis. |
Trombogenesi ex vivo. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Day 0, 3, 14,16 and 21. |
Giorno 0, 3, 14,16 e 21. |
|
E.5.2 | Secondary end point(s) |
Patient health-related quality of life. |
Valutazione della qualità di vita del paziente. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Day 0, 14 and 21. |
Giorno 0, 14 e 21. |
|
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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
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
| Yes |
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 | No |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |