Atypical haemolytic uraemic syndrome (aHUS) MedDRA version: 20.0 Level: PT Classification code 10018932 Term: Haemolytic uraemic syndrome System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Sponsors
Akari Therapeutics Plc,
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.18 years and older at the time of consent. 2.LDH at screening or at the onset of the current aHUS episode was = 1.5 ULN. 3.Platelet count at screening or at the onset of the current aHUS episode =65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: 1.Thrombotic Thrombocytopenic Purpura (TTP), defined as ADAMTS13 activity <10% from an historical observation (prior to initiation of Plasma Therapy) or as tested at the screening visit. 2.STEC HUS (known Shiga toxin positive or EHEC (En-terohaemorrhagic Escherichia coli)) positive cultures. 3.HUS related to known HIV infection. 4.Identified drug exposure-related HUS. 5.HUS related to bone marrow transplant (BMT). 6.HUS related to Cobalamin (vitamin B12) deficiency. 7.Patients with a confirmed diagnosis of sepsis defined as positive blood cultures within 7 days of the screening visit and not treated with antibiotics to which the organism is sensitive. 8.Presence or suspicion of active and untreated systemic bacterial infection that, in the opinion of the Investigator confounds an accurate diagnosis of aHUS or impedes the ability to manage the aHUS disease. 9.Unresolved meningococcal disease. 10.Known Systemic Lupus Erythematosus (SLE) or antiphospholipid antibody positivity or syndrome. 11.Prior use of eculizumab (Soliris®) within 2 months of screening is prohibited. 12.Exposure to any other investigational drug acting directly on the complement system within 5 half-lives of screening is prohibited. 13.Chemotherapeutic agents within 3 months of enrolment in the study are prohibited. 14.History of malignancy within 5 years of screening. 15.Known sensitivity to the excipients of meningococcal vaccines, ciprofloxacin or any other antibiotic being administered for purposes of meningitis prophylaxis. 16.Participation in other clinical trials within 4 weeks of signing the ICF. 17.Known allergy to ticks or severe reaction to arthropod venom (e.g. bee or wasp venom). 18.History of active systemic autoimmune diseases other than the target condition. Dermatologic diseases such as psoriasis will not be a reason for exclusion unless there are associated systemic symptoms such as arthritis. 19.Any severe systemic disorder that could interfere with the evaluation of the study treatment (e.g. hepatic disease) that in the opinion of the Investigator would affect the outcome of the study or interfere with interpretation of results. 20.Failure to satisfy the Investigator of fitness to participate for any other reason or any condition (e.g. severe depression or psychiatric disorder) which, in the opinion of the investigator, could increase the subject's risk by participating in the study or confound the outcome of the study. 21.If female, the subject is pregnant or lactating or intending to become pregnant before, during, or within 18 weeks after last dose; or intending to donate ova during such period. 22.If male, the subject intends to donate sperm during this study or for 90 days after last dose. 23.The subject is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (e.g. spouse, parent, child, sibling) or may consent under duress. 24. The subject has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year prior to screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy and safety of Coversin in adult subjects with aHUS.; Secondary Objective: 1.Evaluate efficacy based on complete Thrombotic Micro An-giopathy (TMA) response, haematological response and TMA event rate. 2.Evaluate additional efficacy end points, such as the effect of Coversin on haematological and renal function over study period. 3.Describe the pharmacokinetics (PK) and pharmacodynamics (PD) of Coversin in subjects with aHUS. 4.Determine the effective dose (ED) and frequency of dosing for the treatment of aHUS. 5.Evaluate safety of Coversin in aHUS. ; Primary end point(s): Proportion of subjects with Normal Platelets count at day 180 [ defined as Platelet count = 150x10*9/L. Safety endpoints Safety analysis will be performed using the safety analysis set. ;Timepoint(s) of evaluation of this end point: Day 180 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.Complete TMA response with preserved renal function: Proportion of patients who achieve complete TMA response with preserved renal function, defined as hematologic normalization (platelet count =150 X 109/L and LDH = ULN) and preservation of kidney function (<25% increase in SCr from baseline), confirmed by two or more consecutive measurements obtained four or more weeks apart. 2.Complete TMA response with improved renal function: Proportion of Patients with Complete TMA response with improved renal function defined as normalization of haematological parameters (normalisation of platelet count and LDH=ULN) and = 25% improvement in SCr from baseline which was sustained for at least two consecutive measurements obtained at least four weeks apart from each other. 3.Proportion of subjects with TMA event free status. 4.(Dialysis events occurring within the 14 days after the first dose of IMP will not be considered as a new Treatment Period dialysis event. In addition, dialysis events that commence within the 14 days before the first dose of IMP and continue up to 14 days after the first dose of IMP will not be considered a new Treatment Period dialysis event). 5.Time to complete TMA response with improved renal function. 6.Platelet count change from baseline to the end of Day 180. 7.Proportion of subjects with Hematologic Normalization defined as normalization of both platelet count and LDH sustained for at least two consecutive measurements obtained at least four weeks apart from each other. 8.Proportion of subjects with normalisation of platelet count at Day 30, Day 90 and Day 180 defined as a platelet count =150 x 109/L. 9.Improvement in renal function defined as a decrease in SCr over three consecutive measurements without the need for dialysis even if not within the normal range. 10. | — |
Countries
United Kingdom
Contacts
Public Contact24 Hour Medical Contact
Akari Therapeutics, Plc
Outcome results
None listed