A Phase III, Randomized, Multi-Center, Open-Label, Active-Comparator Controlled Study to to Evaluate the Efficacy and Safety of APL-2 in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH)

Phase 3

Withdrawn

Conditions: disease of the blood with a too quick destruction of red blood cells in the bloodstream
10038158

Registration Number: NL-OMON46308

Lead Sponsor: Apellis Pharmaceuticals, Inc

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Withdrawn

Sex: Not specified

Target Recruitment: 5

Inclusion Criteria

2. Primary diagnosis of PNH confirmed by high-sensitivity flow cytometry
3. On treatment with eculizumab. Dose of eculizumab must have been stable for at least 3 months prior to the Screening Visit
4. Hb <10.5 g/dL at the Screening Visit
5. Absolute reticulocyte count > 1.5x ULN at the Screening Visit
6. Platelet count of >50,000/mm3 at the Screening Visit
7. Absolute neutrophil count >500/mm3 at the Screening Visit

Exclusion Criteria

1. Active bacterial infection within 4 weeks prior to Day -28 (Run-in Period)
2. Receiving iron, folic acid, vitamin B12 and EPO, unless the dose is stable, in the 4 weeks prior to Screening
3. Hereditary complement deficiency
4. History of bone marrow transplantation
5. History or presence of hypersensitivity or idiosyncratic reaction to compounds related to the investigational product or SC administration
6. Participation in any other investigational drug trial or exposure to other investigational agent within 30 days or 5 half-lives (whichever is longer)
10. Myocardial infarction, CABG, coronary or cerebral artery stenting and /or angioplasty, stroke, cardiac surgery, or hospitalization for congestive heart failure within 3 months or greater than Class 2 Angina Pectoris or NYHA Heart Failure Class >2
11. QTcF > 470 ms, PR > 280 ms
12. Mobitz II 2nd degree AV Block, 2:1 AV Block, High Grade AV Block, or Complete Heart Block unless the patient has an implanted pacemaker or implantable cardiac defibrillator (ICD) with backup pacing capabilities
13. Receiving Class 1 or Class 3 antiarrhythmic agents, or arsenic, methadone, ondansetron or pentamidine at screening

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary objectives of this study are to establish the efficacy and safety<br /><br>of APL-2 compared to eculizumab in patients with PNH who continue to have Hb<br /><br>levels <10.5 g/dL despite treatment with eculizumab.<br /><br>Primary Efficacy Endpoint<br /><br>* Week 16 change from baseline in hemoglobin level</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary Efficacy Endpoints<br /><br>* Week 16 change from baseline in reticulocyte count<br /><br>* Week 16 change from baseline in lactate dehydrogenase (LDH) level<br /><br>* Week 16 change from baseline in FACIT-fatigue scale score<br /><br>* Number of PRBC units transfused from Week 4 to Week 16 (Day 28 to Day 112)<br /><br>* Hemoglobin response in the absence of transfusions (Yes/No). Hemoglobin<br /><br>response is defined as a 1g/dL increase in hemoglobin from Baseline at Week 16<br /><br>* Reticulocyte normalization in the absence of transfusions at Week 16<br /><br>(Yes/No). Reticulocyte normalization is defined as the reticulocyte count being<br /><br>below the upper limit of the normal range</p><br>