This is a Phase II, open-label study designed to evaluate the safety, efficacy, and immunogenicity of NM8074 in PNH patients undergoing complement-inhibitor therapy with Soliris.
The proposed study, NM8074-PNH-106, will enroll a planned number of 12 Soliris-treated PNH patients who have been diagnosed with hemolytic anemia and meet the defined inclusion criteria. This study will evaluate the safety, efficacy, and immunogenicity of NM8074 as both a mono- and combination therapy with complement component C5 blocker Soliris. Patients will be evenly divided into two cohorts.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Monitoring of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Adverse events will be graded according to the CTCAE v4.03. If the AE term is not described in the grading scales, the AE severity shall be reported according to the following: Grade I: Mild (awareness of sign or symptom, but easily tolerated) Grade II: Moderate (discomfort sufficient to cause interference with normal activities) Grade III: Severe (incapacitating, with inability to perform normal activities) Grade IV: Life threatening Grade V: Fatal
Time frame: Up to Study Day 105
Number of Participants with Antidrug Antibodies (ADAs) to NM8074
Time frame: Up to Study Day 105
Change from Baseline or Percent Change from Baseline in Hemoglobin (Hgb) Levels
Time frame: Up to Study Day 105
Change from Baseline or Percent Change from Baseline in Lactate Dehydrogenase (LDH) Levels
Time frame: Up to Study Day 105
Change from Baseline or Percent Change from Baseline in Number of Packed Red Blood Cell (pRBC) Transfusions
Time frame: Up to Study Day 105
Percent Change from Baseline in Levels of Membrane Attack Complex (MAC) via Alternative Pathway (AP) of Complement Activity as Compared to Percent Change from Baseline in Levels of MAC via Classical Pathway (CP) of Complement Activity
Time frame: Up to Study Day 105
Percent Change from Baseline in Levels of Complement Component C3b via Alternative Pathway (AP) of Complement Activity as Compared to Percent Change from Baseline in Levels of C3b via Classical Pathway (CP) of Complement Activity
Time frame: Up to Study Day 105
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Change from Baseline or Percent Change from Baseline in Reticulocyte Count
Time frame: Up to Study Day 105
Change from Baseline or Percent Change from Baseline in Bilirubin Levels
Time frame: Up to Study Day 105
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.
The FACIT-fatigue scale is a 13-item patient-reported measure of fatigue with a 7-day recall period. Items are scored on a 0 - 4 response scale ranging from "Not at all" to "Very much so". All items are summed to create a single fatigue score with a range from 0 to 52 with a better quality of life indicated by a higher score.
Time frame: Up to Study Day 105
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.
All EORTC QLQ-C30 scales and single-item measures range from 0 to 100. This includes 3 symptom scales (fatigue, pain, nausea and vomiting), 5 functional scales (physical, role, cognitive, emotional, and social), single-item questions addressing symptoms like insomnia, dyspnea, loss of appetite, and others that are commonly reported by cancer patients, and the perceived financial impact of the disease. A higher score is associated with a greater quality of life for global health status.
Time frame: Up to Study Day 105
Changes in plasma concentration of NM8074
Time frame: Up to Study Day 105
Maximum plasma concentration (Cmax)
Time frame: Up to Study Day 105
Time corresponding to Cmax (tmax)
Time frame: Up to Study Day 105
Area Under the Drug Concentration-Time Curves (AUC0-t)
Time frame: Up to Study Day 105