Health Condition 1: D593- Hemolytic-uremic syndrome
Conditions
Interventions
Intervention1: NM8074: IV administration Cohort 2: 10 mg/kg weekly for 4 doses and 20 mg/kg biweekly for 5 doses. Follow up for 105 Days.
Control Intervention1: NM8074: IV administration Cohort 1: 20
Sponsors
NovelMed Therapeutics
Ablenio Sciences Private Limited
Eligibility
Inclusion criteria
Inclusion criteria: 1. Patients, 14 Years and older, with evidence of complement-mediated aHUS with symptoms of thrombocytopenia, hemolysis, reduced eGFR, elevated serum creatinine, and kidney injury 2. Male or female = 14 years of age and weighing = 45 kg at the time of consent 3. Platelets less than 150,000 per microliter (thrombocytopenia) and Microangiopathic hemolysis leading to thrombocytopenia, hemolysis, and decreased kidney function 4. Prescence of Schistocytes 5. Decreased level of haptoglobin and hemoglobin (Hemoglobin =10 g/dL) 6. Lactate dehydrogenase (LDH) level = 1.5 times the upper limit of normal (xULN) during Screening. 7. Negative for Shiga toxin induced HUS (STEC-HUS) 8. ADAMTS13 activity greater than 10% 9. Negative (-) direct Coombs test 10. Detectable complement gene mutation (eg. Complement Factor H or Complement Factor I) 11. All patients must be vaccinated prior to dosing with MenACWY Menactra® polysaccharide diphtheria toxoid conjugate vaccination against Neisseria meningitidis serogroups A, C, Y, and W-135 and MenB meningococcal serogroup B vaccine (Bexsero®). If the window of vaccination is short, then patients will be prophylactically treated with appropriate antibiotics. 12. Willing and able to understand and complete informed consent procedures, including signing and dating the informed consent form (ICF), and complying with the study visit schedule. 13. Female partners of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, must have a negative pregnancy test at screening and must agree to use highly effective methods of contraception during dosing and for 1 month after stopping the investigational drug. 14. Male patients and partners of child-bearing potential must agree to use contraceptives and male patients must agree to refrain from donating sperm for the duration of the study.
Exclusion criteria
Exclusion criteria: 1. History of bone marrow, hematopoietic stem cell, or solid organ transplantation 2. History or current treatment with complement blockers 3. Patients with infections 4. HUS due to 13 (ADAMTS-13) deficiency ( 5. Kidney disease other than aHUS 6. Chronic dialysis (hemo or peritoneal) 7. Liver disease or other major autoimmune diseases 8. Positive direct Coombs test 9. Shiga toxin related hemolytic uremic syndrome 10. Known Systemic Lupus Erythematosus (SLE), Systemic Sclerosis, or antiphospholipid antibody positivity or syndrome 11. History of currently active primary or secondary immunodeficiency 12. Identified drug exposure-related HUS or HUS related to known genetic defects of cobalamin C metabolism or known diacylglycerol kinase e (DGKE) mediated aHUS 13. Currently active systemic infection or suspicion of active bacterial, viral, or fungal infection within 2 weeks prior to first dose, or history of unexplained, recurrent bacterial infections 14. Has a currently active or known history of meningococcal disease or N. meningitidis infection 15. Severe concurrent co-morbidities not amenable to active treatment, e.g., patients with severe kidney disease (CKD stage 4, chronic dialysis) 16. Pregnant, planning to become pregnant, or nursing female subjects. 17. Females who have a positive pregnancy test result at Screening or on Day 1.
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Area Under the Drug Concentration-Time Curves (AUC0-t)Timepoint: Baseline, Week 16;Change from Baseline or Percent Change from Baseline in blood clotsTimepoint: Baseline, Week 16;Change from Baseline or Percent Change from Baseline in dialysis requirementTimepoint: Baseline, Week 16;Change from Baseline or Percent Change from Baseline in eGFRTimepoint: Baseline, Week 16;Change from Baseline or Percent Change from Baseline in the total number of plasma infusions or exchangesTimepoint: Baseline, Week 16;Change from Baseline or Percent Change from Baseline in Complement Component Factor B LevelsTimepoint: Baseline, Week 16;Change from Baseline or Percent Change from Baseline in HaptoglobinTimepoint: Baseline, Week 16;Change from Baseline or Percent Change from Baseline in Lactate Dehydrogenase (LDH) LevelsTimepoint: Baseline, Week 16;Change from Baseline or Percent Change from Baseline in Platelet CountTimepoint: Baseline, Week 16;Change from Baseline or Percent Change from Baseline in Quality of Life (QoL) Survey Assessed via the European Organization for Research & Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 Scale (QLQ- C30), Version 3.0.Timepoint: Baseline, Week 16;Change from Baseline or Percent Change from Baseline in Quality of Life (QoL) Survey Assessed via the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale, Version 4.Timepoint: Baseline, Week 16;Change from Baseline or Percent Change from Baseline in SchistocytesTimepoint: Baseline, Week 16;Change from Baseline or Percent Change from Baseline in Serum CreatinineTimepoint: Baseline, Week 16;Changes in plasma concentration of NM8074Timepoint: Baseline, Week 16;Maximum plasma concentration (Cmax)Timepoint: Baseline, Week 16;Monitoring of Adverse Events (AEs) & Serious Adverse Events (SAEs)Timepoint: Baseline, Week 16;Number of Participants with Antidrug Antibodies (ADAs) to NM8074Timepoint: Baseline, Week 16;Percent Change from Baseline in Levels of | — |
Primary
| Measure | Time frame |
|---|---|
| Change from Baseline or Percent Change from Baseline in Hemoglobin (Hgb) LevelsTimepoint: Baseline, Week 16 | — |
Countries
India
Contacts
Public ContactPawan Kumar
Ablenio Sciences Private Limited
Outcome results
None listed