Clinical trial NCT02264639: A Phase I Study to Assess the Safety of Pegcetacoplan (APL-2) as an Add-On to Standard of Care in Subjects With PNH
Official title: An Open Label, Single and Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of APL-2 as an Add-On to Standard of Care in Subjects With Paroxysmal Nocturnal Hemoglobinuria (PNH).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH)
Keywords: PNH
Paroxysmal Nocturnal Hemoglobinuria
Complement inhibitor
Anemia
Hemoglobinuria
hematologic diseases
extravascular hemolysis (EVH)
intravascular hemolysis (IVH)
C3 inhibitor
Lead sponsor: Apellis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2014-10-15
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will be the initial exploration of pegcetacoplan in patients with PNH. The assessments of the safety, tolerability, PK, and PD following administration of single and multiples doses of pegcetacoplan will guide decisions to further develop the drug.


Eligibility criteria: Inclusion Criteria:

* Male or Female
* At least 18 years of age
* Weigh \>55 kg
* Diagnosed with PNH
* On treatment with eculizumab (Soliris®) for at least 3 months
* Hb \< 10 g/dL at screening OR have received at least one transfusion within 12 months prior to screening
* Platelet count of \>30,000/mm3
* Absolute neutrophil count \> 500/mm3
* 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 (see below)
* Males with female partners of child bearing potential must agree to use protocol defined methods of contraception (see below) and agree to refrain from donating sperm for the duration of the study
* Willing and able to give informed consent

Exclusion Criteria:

* Active bacterial infection
* Known infection with hepatitis B, C or HIV
* Hereditary complement deficiency
* History of bone marrow transplantation
* Participation in any other investigational drug trial or exposure to other 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
* No vaccination against N. meningitidis types A, C, W, Y and B (administered as two separate vaccinations), Pneumococcal conjugate vaccine or Pneumococcal polysaccharide vaccine 23 (PCV13 or PPSV23, respectively) and Haemophilus influenzae Type B (Hib) vaccination within 2 years prior to Day 1 (Visit 2) dosing.

Primary outcomes:
measure: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Including by Severity, During Single-dose Phase
timeFrame: From single dose of study drug (Day 1) up to 30 days
measure: Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase
timeFrame: From first dose of study drug up to 30 days after last dose of study drug (Cohorts 1-3: up to 58 days; Cohort 4: up to 759 days).
measure: Area Under the Curve (AUC) From Time 0 to the Last Measurable Concentration (AUC0-t) Over the Multiple Dosing Phase for Cohort 4
timeFrame: Blood samples for PK assessment were collected pre-dose and 4 hours post dose on Day 1 and pre-dose (trough) on Day 2 and up to Day 785.
measure: Maximum Pre-dose Serum Concentration (Ctrough,Max) Over the Multiple Dosing Phase for Cohort 4
timeFrame: Blood samples for PK assessment were collected pre-dose and 4 hours post dose on Day 1 and pre-dose (trough) on Day 2 and up to Day 785.
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California Norris Comprehensive Cancer Center
state: California
city: Miami Lakes
country: United States
facility: Lakes Research
state: Florida
city: Louisville
country: United States
facility: University of Lousiville
state: Kentucky
city: Baltimore
country: United States
facility: John Hopkins Hospital
state: Maryland
city: Las Vegas
country: United States
facility: Cure 4 The Kids Foundation
state: Nevada
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
Study officials:
affiliation: Apellis Pharmaceuticals, Inc.
name: Federico Grossi, MD, PhD
role: STUDY_DIRECTOR
References: