Paroxysmal Nocturnal Hemoglobinuria (PNH) MedDRA version: 20.1 Level: LLT Classification code 10055629 Term: Paroxysmal nocturnal hemoglobinuria System Organ Class: 100000004857
Conditions
Interventions
Product Name: APL-2
Product Code: APL-2
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: pegcetacoplan
CAS Number: 2019171-69-6
Current Sponsor code: APL-2
Other descriptive n
Sponsors
Apellis Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: At Visit 1 screening, subjects must fulfill all of the following inclusion criteria to be eligible for participation in the study: 1. Be at least 18 years old (inclusive). 2. Have LDH =1.5 x ULN at the screening visit. 3. Have PNH diagnosis, confirmed by high sensitivity flow cytometry (granulocyte or monocyte clone >10%). 4. Have Hb less than the lower limit of normal (LLN) at the screening visit. 5. Have ferritin greater than/equal to the LLN, or total iron binding capacity (TIBC) less than/equal to ULN at the screening visit, based on central laboratory reference ranges. If a subject is receiving iron supplements at screening, the Investigator must ensure that the subject’s dose has been stable for 4 weeks prior to screening, and it must be maintained throughout the study. Subjects not receiving iron at screening must not start iron supplementation during the course of the study. 6. Body mass index (BMI) = 35 kg/m2 at the screening visit. 7. Have a platelet count of >50,000/mm3 at the screening visit. 8. Have an absolute neutrophil count >500/mm3 at the screening visit. 9. Women of child-bearing potential (WOCBP) must have a negative pregnancy test at screening and must agree to use protocol-defined methods of contraception for the duration of the study and for 90 days after their last dose of study drug. 10. Males must agree to use protocol-defined methods of contraception and agree to refrain from donating sperm for the duration of the study and for 90 days after their last dose of study drug. 11. Have vaccination against Streptococcus pneumoniae, Neisseria meningitides (types A, C, W, Y, and B), and Haemophilus influenzae (type B) either within 2 years prior to Day 1 dosing, or agree to receive vaccination 14 days after starting treatment with APL-2 (along with prophylactic antibiotic therapy for at least the 14 days between APL-2 treatment initiation and vaccination and for 14 days post vaccination). Vaccination is mandatory, unless documented evidence exists that subjects are non-responders to vaccination (as evidenced by titers or display titer levels within acceptable local limits). 12. Be willing and able to give informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 27 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 27
Exclusion criteria
Exclusion criteria: Subjects will be excluded from the study if there is evidence of any of the following criteria at screening: 1. Treatment with any complement inhibitor (eg, eculizumab) within 3 months prior to screening. 2. Hereditary complement deficiency. 3. History of bone marrow transplantation. 4. Concomitant use of any of the following medications is prohibited if not on a stable regimen for the time period indicated below prior to screening: • Erythropoietin or immunosuppressants for at least 8 weeks • Systemic corticosteroids for at least 4 weeks • Vitamin K antagonists (eg, warfarin) with a stable international normalized ratio (INR) for at least 4 weeks • Iron supplements, vitamin B12, or folic acid for at least 4 weeks • Low-molecular-weight heparin for at least 4 weeks 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, device, or procedure within 30 days or 5 half-lives, whichever is longer. 7. Planning to become pregnant or currently a breast-feeding woman. 8. History of meningococcal disease. 9. Any comorbidity or condition (such as malignancy) that, in the opinion of the Investigator, could put the subject at increased risk or potentially confound study data.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate the efficacy of APL-2, compared to SOC (excluding complement inhibitors), in patients with PNH, as assessed by: • Hemoglobin stabilization defined as avoidance of a > 1 g/dl decrease in Hb levels from Baseline in the absence of transfusion through Week 26 (Yes/No) AND • Reduction in lactate dehydrogenase (LDH) level from Baseline to Week 26;Secondary Objective: • To evaluate the efficacy of APL-2, compared to SOC (excluding complement inhibitors), as assessed by: o Hemoglobin response in the absence of transfusions (Hb response defined as a =1g/dL increase in Hb from Baseline at Week 26) o Change from Baseline to Week 26 (W 26) in absolute reticulocyte count o Change from Baseline to W 26 in Hb level o Number of PRBC units transfused from Baseline to W 26 o Change from Baseline to W 26 in FACIT- Fatigue Scale score o Normalization of Hb levels (=1x ULN) from Baseline at W 26 in the absence of transfusions o Normalization of LDH levels of =1 x the upper limit of normal from Week 4 to W 26 in the absence of transfusions o Change from Baseline to W 26 in EORTC QLQ-C30 scores o Change from Baseline to W 26 in LASA scale scores o Change from Baseline to W 26 in LDH level o Absolute reticulocyte count normalization ( 1 g/dl decrease in Hb levels from Baseline in the absence of transfusion through Week 26 (Yes/No) AND Reduction in lactate dehydrogenase (LDH) level from Baseline to Week 26;Timepoint(s) of evaluation of this end point: from Baseline through Week 26 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy end points: o Hemoglobin response (Yes/No) in the absence of transfusions (Hb response is defined as a =1g/dL increase in Hb from Baseline at Week 26) o Change from Baseline to Week 26 in absolute reticulocyte count o Change from Baseline to Week 26 in Hb level o Number of packed red blood cell (PRBC) units transfused from Baseline to Week 26 o Change from Baseline to Week 26 in Functional Assessment of Chronic Illness Therapy- (FACIT-) Fatigue Scale score o Normalization of Hb levels (defined as =1x ULN) from Baseline at Week 26 in the absence of transfusions (Yes/No) o Normalization of LDH levels of =1 x the upper limit of normal (ULN) from Week 4 to Week 26 in the absence of transfusions (Yes/No) o Change from Baseline to Week 26 in European Organization for Research and Treatment of Cancer (EORTC) 30-item Core Quality of Life Questionnaire (QLQ C30) scores (Version 3) o Change from Baseline to Week 26 in Linear Analog Assessment (LASA) scale scores o Change from Baseline to Week 26 in LDH level o Absolute reticulocyte count normalization (<1 x ULN) at Week 26 (Yes/No) o Time of failure of Hb stabilization o Time to transfusion Safety end points: o Incidence and severity of treatment-emergent adverse events (TEAEs) o Incidence of thromboembolic events o Changes from Baseline in laboratory parameters o Changes from Baseline in ECG parameters o Incidence of anti-APL2 antibodies;Timepoint(s) of evaluation of this end point: from Baseline to Week 26 | — |
Countries
Argentina, Brazil, Colombia, Hong Kong, Hungary, Malaysia, Mexico, Peru, Philippines, Poland, Serbia, Thailand
Contacts
Public ContactClinical Trials Information
Argint International Clinical Research & Development Services Kft.
Outcome results
None listed