Clinical trial NCT03593200: A Phase IIa Study to Assess the Safety, Efficacy, and Pharmacokinetics of Subcutaneously Administered Pegcetacoplan (APL-2) in Subjects With PNH
Official title: Phase IIa, Open Label, Multiple Dose Study to Assess the Safety, Efficacy and Pharmacokinetics of Subcutaneously Administered APL-2 in Subjects With Paroxysmal Nocturnal Hemoglobinuria (PNH).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: PNH
Keywords: PNH
Paroxysmal Nocturnal Hemoglobinuria
Complement inhibitor
Anemia
Hemoglobinuria
Hemolysis
Hematologic diseases
Extravascular hemolysis (EVH)
Intravascular hemolysis (IVH)
C3 inhibitor
Lead sponsor: Apellis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2018-07-20
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a Phase IIa, open-label, multiple dose, study in patients with PNH who have not received eculizumab (Soliris ®) in the past. A single cohort of subjects is planned for evaluation.


Eligibility criteria: Inclusion Criteria:

* At least 18 years old (inclusive)
* Diagnosed with PNH (white blood cell (WBC) clone \>10%)
* Lactose dehydrogenase (LD) ≥2 times the upper limit of normal
* Screening Ferritin ≥ normal and Total Iron Binding Capacity (TIBC) \< LLN based on central lab reference ranges. If a subject is receiving iron supplements at screening, the investigator must ensure that his/her dose has been stable for 8 weeks prior to enrolment and must be maintained throughout the study
* Last transfusion within 12 months prior to screening
* Platelet count of \>30,000/mm3 at the screening visit
* Absolute neutrophil count \>500/ mm3 at the screening visit
* 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
* Vaccination against Neisseria meningitides types A, C, W, Y and B, Streptococcus pneumoniae and Haemophilus influenzae Type B (Hib) either within 2 years prior to Day 1 dosing, or within 14 days after starting treatment with pegcetacoplan. Unless documented evidence exists that subjects are non-responders to vaccination as evidenced by titers or display titer levels within acceptable local limits
* Willing and able to give informed consent

Exclusion Criteria:

* Prior eculizumab (Soliris®) treatment
* Active bacterial infection
* 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
* Breast-feeding women
* History of meningococcal disease

Primary outcomes:
measure: Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity
timeFrame: From Day 1 to 30 days after the last dose (approximately 56 weeks)
measure: Mean Change From Baseline in Lactate Dehydrogenase (LDH) Level
timeFrame: Baseline and Day 365
measure: Mean Change From Baseline in Haptoglobin Level
timeFrame: Baseline and Day 365
measure: Mean Change From Baseline in Hemoglobin (Hb) Level
timeFrame: Baseline and Day 365
Secondary outcomes:
measure: Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score
timeFrame: Baseline and Day 365
measure: Mean Change From Baseline in Absolute Reticulocyte Count (ARC) Level
timeFrame: Baseline and Day 365
measure: Mean Change From Baseline in Total Bilirubin Level
timeFrame: Baseline and Day 365
measure: Mean Number of Red Blood Cell (RBC) Transfusions Per Month
timeFrame: From Day 1 to Day 364
measure: Mean Change From Baseline in Linear Analog Scale Assessment (LASA) Score for QoL
timeFrame: Baseline and Day 365
measure: Mean Serum Concentrations of Pegcetacoplan
timeFrame: Day 365
measure: Mean Area Under the Serum Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration at the End of the Study (AUCtotal)
timeFrame: Blood samples were collected predose and at least 2.5 hours post dose on Day 1 and predose on Days 2 up to Day 365.
measure: Mean Maximum Observed Predose Serum Concentration During the Study (Ctrough,Max,Total)
timeFrame: Blood samples were collected predose and at least 2.5 hours post dose on Day 1 and predose on Days 2 up to Day 365.
Other outcomes:
Locations:
city: Sofia
country: Bulgaria
facility: Acibadem City Clinic MHAT Tokuda EAD Sofia
city: Sofia
country: Bulgaria
facility: Specialized Hospital for Active Treatment of Hematologic Diseases EAD, Sofia
city: Belgrade
country: Serbia
facility: Klinički centar Srbije
Study officials:
affiliation: Study Director
name: Federico Grossi, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Wong RSM, Pullon HWH, Amine I, Bogdanovic A, Deschatelets P, Francois CG, Ignatova K, Issaragrisil S, Niparuck P, Numbenjapon T, Roman E, Sathar J, Xu R, Al-Adhami M, Tan L, Tse E, Grossi FV. Inhibition of C3 with pegcetacoplan results in normalization of hemolysis markers in paroxysmal nocturnal hemoglobinuria. Ann Hematol. 2022 Sep;101(9):1971-1986. doi: 10.1007/s00277-022-04903-x. Epub 2022 Jul 22.