A study of Safety and Efficacy of Coversin in adult aHUS subjects

• Register: EUCTR
• Last refreshed on: 16 December 2019
• Main ID: EUCTR2017-000064-15-GB
• Date of registration: 28/06/2017
• Prospective Registration: Yes
• Primary sponsor: Akari Therapeutics Plc,
• Public title: A study of Safety and Efficacy of Coversin in adult aHUS subjects
• Scientific title: A Phase 2, single arm study of Safety and Efficacy of Coversin in adult aHUS subjects
• Date of first enrolment: 14/09/2017
• Target sample size: 10
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-000064-15
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

United Kingdom

Contacts

• Name: 24 Hour Medical Contact
• Affiliation: Akari Therapeutics, Plc

• Name: 24 Hour Medical Contact
• Affiliation: Akari Therapeutics, Plc

Key inclusion & exclusion 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 < 150 X 10*9/L.
4.Evidence of AKI as per KDIGO guidelines [1]. (Increase in SCr by = 0.3 mg/dl (26.5 µmol/l) within 48 hours; or Increase in SCr to = 1.5 times baseline, which is known or presumed to have occurred within the prior 7 days, OR Urine volume 0.5 ml/kg/h for 6 hours.
5.Males and females of childbearing potential must agree to use an adequate method of contraception. Females will have a negative serum pregnancy test before entry to the study and throughout the study.
6.The patient has given voluntary written informed consent.
7. Willing to receive immunisation against Neisseria meningitidis and antibiotic prophylaxis in accordance with the KDIGO guidelines and local standard of care of the PI at each trial site.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 8
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

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.





Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

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

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: Coversin
Product Code: rVA576
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Coversin
Current Sponsor code: rVA576
Other descriptive name: COVERSIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 18-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Day 180

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.

Main Objective: To evaluate the efficacy and safety of Coversin in adult subjects with 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.

Secondary Outcome(s)

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.Reduction in requirement for dialysis defined as proportion of patients who discontinued dialysis for a period of 12 consecutive weeks from those who required dialysis at inclusion.
11.Major Adverse Vascular Events (MAVE) rate during the pre-treatment period versus rate after the first dose of Investigational Product.
12.Safety for Coversin therapy as assessed by AEs, adverse events of special interest (AESIs, including serious infections, including Neisseria infections, malignancies and injection site reactions and hypersensitivity), serious adverse events (SAEs), vital signs, results of standard laboratory tests (clinical
chemistry, haematology and urinalysis), and results of 12 lead electrocardiograms (ECGs).

Timepoint(s) of evaluation of this end point: -Two consecutive measurements obtained at least four weeks apart from each other (TMA response).
-Day 30, Day 90, Day 180 (platelet count).
-Three consecutive measurements (renal function).
-12 consecutive weeks (reduction of dialysis).
-After first dose of IMP (MAVE).

Secondary ID(s)

AK601

Source(s) of Monetary Support

Akari Therapeutics, Plc

Ethics review

Status: Approved
Approval date:
Contact: