Safety and Efficacy of Coversin in adult aHUS subjects

Phase 2

Conditions: Hemolytic-uremic syndrome,

Registration Number: CTRI/2018/12/016521

Lead Sponsor: Akari Therapeutics Plc

Brief Summary: Atypical Haemolytic Uraemic Syndrome (aHUS) is a rare, genetic, progressive and life threatening disease which results from uncontrolled activation of the complement system leading to thrombotic microangiopathy (TMA) and subsequently severe renal damage, loss of kidney function and sometimes death. The current standard of care in India is plasma exchange or plasma infusion, dialysis, and kidney transplantation. A humanized monoclonal antibody which inhibits the complement system by binding on C5 molecule has shown to be effective in the treatment of aHUS and has been approved for the treatment of aHUS in many countries globally since 2011 but is not available to patients in India currently. Eculizumab has been shown to improve the morbidity and mortality in aHUS patients significantly.

rVA576 is a naturally derived compound (from tick saliva) that also acts as a complement inhibitor but binds to different site domain on C5 molecule. It is designed to be self-administered via a daily subcutaneous injection.

The current standard of care in India for aHUS treatment is plasma exchange and dialysis. These treatment options are associated with significant morbidity and mortality and a complement inhibitor therapy has potential to change the treatment pathway for aHUS patients in India. Compared to standard of care of plasma exchange and dialysis, the rVA576 as a terminal complement inhibitor is hoped to improve morbidity and mortality in aHUS patients

Detailed Description: Not available

Recruitment & Eligibility

Status: Other

Sex: All

Target Recruitment: 10

Inclusion Criteria

18 years and older at the time of consent 2.
LDH at screening or at the onset of the current aHUS episode was â‰¥ 1.5 ULN 3.
Platelet count at screening <150 X 109/ L 4.
Evidence of AKI as per KDIGO guidelines.
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.
Women of child-bearing potential are considered to remain so following menarche until becoming post-menopausal unless permanently sterilised.
Permanent sterile methods include hysterectomy, bilateral salpingectomy, bilateral oophorectomy.
Postmenopausal state is defined as no menses for 12 months without an alternative cause.
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 8.
The patient is willing to comply with the process of preparation and self-administration of the study drug.

Exclusion Criteria

Thrombotic Thrombocytopenic Purpura (TTP), defined as ADAMTS13 activity <10% from a historical observation (prior to initiation of PT) or as tested at the screening visit.
Typical HUS (known Shiga toxin + or positive EHEC culture) 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 (SolirisÂ®) 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).

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Proportion of subjects with Normal Platelet count at Day 180	Day 180

Secondary Outcome Measures

Name	Time	Method
Complete TMA response with preserved renal function and improved renal function. Proportion of subjects with TMA event free status. Time to complete TMA response with improved renal function. Platelet mean count change.Proportion of subjects with Hematologic Normalization.Proportion of subjects with normalisation of platelet count.Proportion of subjects with improvement in renal function.Reduction in requirement for Dialysis. Major Adverse Vascular Events (MAVE) rate.Safety for Coversin.	Day 30, Day 60, Day 90, Day120, Day 150, Day 180.

Trial Locations

Locations (3): All India Institutes of Medical Sciences (AIIMS)
🇮🇳
Delhi, DELHI, India
KEM Hospital
🇮🇳
Pune, MAHARASHTRA, India
Seth G.S.M.C and KEM hospital
🇮🇳
Mumbai, MAHARASHTRA, India
All India Institutes of Medical Sciences (AIIMS)
🇮🇳Delhi, DELHI, India
Dr Sanjay K Agarwal
Principal investigator
11-26593292
skagarwalnephro@gmail.com