Health Condition 1: D595- Paroxysmal nocturnal hemoglobinuria [Marchiafava-Micheli]
Conditions
Interventions
Intervention1: NM8074
: IV administration
Cohort 1: 20 mg/kg biweekly for 7 doses
Cohort 2: 10 mg/kg weekly for 4 doses and 20 mg/kg biweekly for 5 doses
Follow up for 133 Days.
the Drug blocks the al
Sponsors
NovelMed Therapeutics
JSS Medical Research
Eligibility
Inclusion criteria
Inclusion criteria: 1. Patients = 18 years (males and females), weight = 45 kg at the time of consent. 2. Confirmation of PNH diagnosis by flow cytometry evaluation white blood cells (WBCs), with neutrophil, granulocyte and/or monocyte clone size of =10%. 3. Evidence of ongoing hemolysis. 4. =1 pRBC transfusion within 12 months prior to screening. 5. Anemia (Hemoglobin =10.5 g/dL). 6. Lactate dehydrogenase (LDH) level = 1.5 times the upper limit of normal (xULN) during Screening. 7. 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. 8. Willing and able to understand and complete informed consent procedures, including signing and dating the informed consent form (ICF), and comply with the study visit schedule.
Exclusion criteria
Exclusion criteria: 1. History of bone marrow, hematopoietic stem cell, or solid organ transplantation 2. History of splenectomy 3. Participation in any other investigational drug trial within 5 elimination half-lives of enrollment, or within 30 days, whichever is longer 4. Subjects currently or previously under other complement inhibitor treatments less than 3 months prior to study Day 1 5. Participants with known or suspected hereditary or acquired complement deficiency 6. History of currently active primary or secondary immunodeficiency 7. 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 8. Has a known history of meningococcal disease or N. meningitidis infection 9. Patients on immunosuppressive agents or systemic corticosteroids less than 8 weeks prior to dosing 10. Known medical or psychological condition(s) or risk factor that, in the opinion of the Investigator, might interfere with the patient’s full participation in the study, pose any additional risk for the patient, or confound the assessment of the patient or outcome of the study. 11. Severe concurrent co-morbidities not amenable to active treatment, e.g., patients with severe kidney disease (CKD stage 4, dialysis) 12. Subjects currently or previously under other complement inhibitor treatments less than 3 months prior to study Day 1. 13. Pregnant, planning to become pregnant, or nursing female subjects. 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 week after stopping the investigational drug. 14. Females who have a positive pregnancy test result at Screening or on Day 1. 15. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from Baseline or Percent Change from Baseline in Hemoglobin (Hgb) LevelsTimepoint: Baseline, Week 20 | — |
Secondary
| Measure | Time frame |
|---|---|
| Area Under the Drug Concentration-Time Curves (AUC0-t)Timepoint: Baseline, Week 20;Change from Baseline or Percent Change from Baseline in Bilirubin Levels Timepoint: Baseline, Week 20;Change from Baseline or Percent Change from Baseline in C3b Deposition on PNH CellsTimepoint: Baseline, Week 20;Change from Baseline or Percent Change from Baseline in Complement Component Factor B LevelsTimepoint: Baseline, Week 20;Change from Baseline or Percent Change from Baseline in Haptoglobin LevelsTimepoint: Baseline, Week 20;Change from Baseline or Percent Change from Baseline in Lactate Dehydrogenase (LDH) LevelsTimepoint: Baseline, Week 20;Change from Baseline or Percent Change from Baseline in Levels of Complement Component C3b via Classical Pathway (CP) of Complement ActivityTimepoint: Baseline, Week 20;Change from Baseline or Percent Change from Baseline in Levels of Membrane Attack Complex (MAC) via Classical Pathway (CP) of Complement Activity Timepoint: Baseline, Week 20;Change from Baseline or Percent Change from Baseline in Number of Packed Red Blood Cell (pRBC) Transfusions Timepoint: Baseline, Week 20;Change from Baseline or Percent Change from Baseline in Platelet CountTimepoint: Baseline, Week 20;Change from Baseline or Percent Change from Baseline in PNH Cell Clone Size Timepoint: Baseline, Week 20;Change from Baseline or Percent Change from Baseline in Quality of Life (QoL) Survey Assessed via the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 Scale (QLQ- C30), Version 3.0.Timepoint: Baseline, Week 20;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 20;Change from Baseline or Percent Change from Baseline in Reticulocyte Count Timepoint: Baseline, Week 20;Changes in plasma concentration of NM8074Timepoint: Baselin | — |
Countries
India
Contacts
Public ContactDr Neeraj Prasad
JSS Medical Research
Outcome results
None listed