Pilot Study to Assess Safety, Preliminary Efficacy and Pharmacokinetics of S.C. APL-2 in PNH Subjects
This trial is active, not recruiting.
|Condition||paroxysmal nocturnal hemoglobinuria|
|Sponsor||Apellis Pharmaceuticals, Inc.|
|Start date||November 2015|
|End date||December 2017|
|Trial size||6 participants|
|Trial identifier||NCT02588833, APL2-CP-PNH-204|
The objectives of the study are to assess the safety, tolerability, preliminary efficacy and PK of multiple subcutaneous (SC) doses of APL-2 in subjects with paroxysmal nocturnal hemoglobinuria (PNH) who have not received treatment with eculizumab in the past.
An exploratory objective of the study is to assess the pharmacodynamics (PD) of multiple SC doses of APL 2 when administered to PNH patients. See "Pharmacodynamic Assessment" below.
|Endpoint classification||safety/efficacy study|
|Intervention model||single group assignment|
180 mg APL-2/day
270 mg APL-2/day
Number of treatment emergent adverse events (TEAEs) following administration of multiple doses of SC APL-2.
time frame: 4 months from baseline
Severity of treatment emergent adverse events (TEAEs) following administration of multiple doses of SC APL-2.
time frame: 4 months from baseline
Male or female participants at least 18 years old.
Inclusion Criteria: - Male or female - At least 18 years old (inclusive) - Weigh >55 kg and have a body mass index (BMI) ≤38.0 kg/m2 - Diagnosed with PNH (white blood cell (WBC) clone >10%) - Lactose dehydrogenase (LD) ≥2 times the upper limit of normal - Last transfusion within 12 months prior to screening - Platelet count of >30,000/mm3 - Absolute neutrophil count >cells/500 µL - 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 - Males must agree to use protocol defined methods of contraception and agree to refrain from donating sperm for the duration of the study - Able to provide documentary evidence of Neisseria meningitidis, Pneumococcal conjugate vaccine (multivalent) or Pneumococcal polysaccharide vaccine 23 (PCV13 or PPSV23) and Haemophilus influenzae Type B (Hib) vaccination within 2 years prior to Day 1 dosing, OR willing to receive vaccinations against Neisseria meningitidis at least two weeks prior to dosing on Day 1 with a booster on Day 57, and PCV13 and Hib vaccines at least two weeks prior to dosing on Day 1. - Willing and able to give informed consent Exclusion Criteria: - Prior eculizumab (Soliris)® treatment - Active bacterial infection - Known infection with hepatitis B, hepatitis C or human immunodeficiency virus (HIV) - Hereditary complement deficiency - History of bone marrow transplantation - Concurrent severe aplastic anemia (SAA), defined as currently receiving immunosuppressive therapy for SAA including but not limited to cyclosporin A, tacrolimus, mycophenolate mofetil or anti-thymocyte globulin. - Participation in any other investigational drug trial or exposure to another investigational agent, device or procedure within 30 days - Evidence of QTcF prolongation defined as >450 ms for males and >470 ms for females at screening - Creatinine clearance (CrCl) <50 mL/min (Cockcroft-Gault formula) at screening - Breast-feeding women - History of meningococcal disease
|Official title||A Phase Ib, Open Label, Multiple Ascending Dose, Pilot Study to Assess the Safety, Preliminary Efficacy and Pharmacokinetics of Subcutaneously Administered APL-2 in Subjects With Paroxysmal Nocturnal Hemoglobinuria (PNH)|
|Description||This is a Phase Ib, open-label, multiple ascending dose, pilot study in patients with PNH who have not received eculizumab (Soliris)® in the past. Two cohorts of 3 subjects are planned for evaluation. Subjects will participate in only one cohort. Safety will be assessed throughout the study; serial blood and urine samples will be collected for these assessments. Blood samples will be collected for the assessment of APL 2 PK. Additional samples for assessment of PD will also be collected. The study will consist of three parts; - Part 1: subjects will receive APL-2 for 28 days. - Part 2: subjects will receive APL-2 for a further 56 days provided there is evidence of hemolytic activity (as defined by an observed decrease in LD to < x2 ULN) - Part 3: Safety follow up Screening will take place within 30 days prior to the start of dosing on Day 1. Neisseria meningitidis, Pneumococcal conjugate vaccine (multivalent) or Pneumococcal polysaccharide vaccine 23 (PCV13 or PPSV23), and Haemophilus influenzae Type B (Hib) vaccinations will be administered at least 14 days prior to dosing on Day 1. Subjects will be entered into Part 1 of the study on Day 1 at a time designated by the PI. During Part 1, the first 3 daily SC doses of APL-2 (day 1 to 3) as well as doses on Day 8, 15 and 22 will be administered at the clinical site. From Day 4 to Day 28 daily doses of APL-2 will be administered by a rained study nurse at the subject's home with the exception of those days where dosing is at the clinical site (see above). Progression to Part 2 of the study will be assessed on a per subject basis; if a reduction in hemolysis is demonstrated by Day 28, the subject will enter Part 2 of the study and continue to receive daily doses of APL 2 until Day 84. Doses will be administered by a study nurse at the subject's home with the exception of Days 29, 36, 43, 57 and 71 where dosing is at the clinical site. After the conclusion of the treatment period (Day 84), subjects will return to the clinical site for follow-up study procedures on Day 85, 99, and 113 and final study procedures at an Exit Visit on Day 134. If there is no reduction in hemolysis by Day 28, treatment for that subject will stop on Day 28. The subject will skip Part 2 and enter Part 3 for safety follow up visits on Days 29, 43, and 57 and final study procedures at an Exit Visit on Day 78. See Study Flow Chart in Section 2. Cohort 2 will not be initiated until all subjects in Cohort 1 have reached the Day 29 visit and the SMC has reviewed emerging safety and efficacy data and determined that, at the initial dose, APL-2 has an acceptable safety and tolerability profile. Interim PK and PD analyses may be performed to reconsider the sampling time points as the study progresses. The planned length of participation in the study for each subject is approximately 160 days (from Day -30 through completion of the Day 134 Exit visit procedures). The study is planned to take place over 6 to 8 months (from screening of Cohort 1 through completion of Cohort 2). This time period may change in the event that the study is terminated early, additional cohorts are enrolled, additional time is required to review safety between cohorts, or extended safety and PK sampling is added for a cohort (e.g., beyond Day 134).|
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