Study of NM8074 in Adult PNH Patients With Inadequate Response to Soliris

Browse trials for

• Hemoglobinuria, Paroxysmal 188

Study arms

• Experimental
  Cohort 1

  6 Soliris-treated patients will receive an intravenous (IV) dose of NM8074 at 10 mg/kg weekly for 4 weeks. Patients will then discontinue Soliris treatment and be administered NM8074 at 20 mg/kg IV every 2 weeks for the remainder of the treatment period (8 weeks). At the end of the treatment period, patients will resume Soliris monotherapy as prescribed.

  Drug: NM8074 · Drug: Soliris

• Experimental
  Cohort 2

  6 Soliris-treated patients will receive an intravenous (IV) dose of NM8074 at 10 mg/kg for 4 weeks. Patients will then continue receiving Soliris while being administered NM8074 as a combination therapy at 20 mg/kg IV every 2 weeks for the remainder of the treatment period (8 weeks). At the end of the treatment period, patients will resume Soliris monotherapy as prescribed.

  Drug: NM8074 · Drug: Soliris

Interventions

• DrugNM8074

  NM8074 is an anti-Factor Bb humanized monoclonal antibody that will be administered as an intravenous infusion. Doses will be administered over a treatment period of 13 weeks.

• DrugSoliris

  Complement C5 blocker administered intravenously

  Also known as: Eculizumab

Primary outcomes

1. 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

2. Number of Participants with Antidrug Antibodies (ADAs) to NM8074

   Time frame: Up to Study Day 105

3. Change from Baseline or Percent Change from Baseline in Hemoglobin (Hgb) Levels

   Time frame: Up to Study Day 105

4. Change from Baseline or Percent Change from Baseline in Lactate Dehydrogenase (LDH) Levels

   Time frame: Up to Study Day 105

5. Change from Baseline or Percent Change from Baseline in Number of Packed Red Blood Cell (pRBC) Transfusions

   Time frame: Up to Study Day 105

6. 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

7. 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

Secondary outcomes

1. Change from Baseline or Percent Change from Baseline in Reticulocyte Count

   Time frame: Up to Study Day 105

2. Change from Baseline or Percent Change from Baseline in Bilirubin Levels

   Time frame: Up to Study Day 105

3. 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

4. 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

5. Changes in plasma concentration of NM8074

   Time frame: Up to Study Day 105

6. Maximum plasma concentration (Cmax)

   Time frame: Up to Study Day 105

7. Time corresponding to Cmax (tmax)

   Time frame: Up to Study Day 105

8. Area Under the Drug Concentration-Time Curves (AUC0-t)

   Time frame: Up to Study Day 105

Other outcomes

1. Change from Baseline or Percent Change from Baseline in Complement Component Factor B Levels

   Time frame: Up to Study Day 105

2. Change from Baseline or Percent Change from Baseline in Haptoglobin Levels

   Time frame: Up to Study Day 105

3. Change from Baseline or Percent Change from Baseline in Platelet Count

   Time frame: Up to Study Day 105

4. Change from Baseline or Percent Change from Baseline in PNH Cell Clone Size

   Clone size will be measured via fluorescein-labeled proaerolysin (FLAER) staining of WBCs (granulocytes and monocytes)

   Time frame: Up to Study Day 105

5. Change from Baseline or Percent Change from Baseline in C3b Deposition on PNH Cells

   Loading of C3b on erythrocytes will be evaluated using flow cytometry

   Time frame: Up to Study Day 105

6. Change from Baseline or Percent Change from Baseline in Levels of Membrane Attack Complex (MAC) via Classical Pathway (CP) of Complement Activity

   Time frame: Up to Study Day 105

7. Change from Baseline or Percent Change from Baseline in Levels of Complement Component C3b via Classical Pathway (CP) of Complement Activity

   Time frame: Up to Study Day 105

Individual participant data

Plan to share: No