A Phase IIa Study to Assess the Safety, Efficacy, and Pharmacokinetics of Subcutaneously Administered Pegcetacoplan (APL-2) in Subjects With PNH

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).

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.

Study Overview

• Status: Completed
• Conditions: PNH
• Intervention / Treatment: Drug: Pegcetacoplan

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria
    • Acibadem City Clinic MHAT Tokuda EAD Sofia
  • Sofia, Bulgaria
    • Specialized Hospital for Active Treatment of Hematologic Diseases EAD, Sofia
• Serbia
  • Belgrade, Serbia
    • Klinicki Centar Srbije

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: Cohort 1; 270 mg/day (up to 360 mg/day from Day 29) from Day 1 to Day 364*	Drug: Pegcetacoplan; Complement (C3) Inhibitor; Other Names: APL-2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity	TEAEs were defined as adverse events (AE) that occurred after dosing on Day 1 and up to 30 days after the last dose of study drug. A treatment-related TEAE was defined as a TEAE with a relationship to study drug of possible, probable, or definite. TEAEs were graded according to the Common Terminology Criteria for Adverse Events (v4.03) based on: Grade 1: Mild, Grade 2: Moderate, Grade 3: Severe, Grade 4: Life-threatening, Grade 5: Death related to AE.	From Day 1 to 30 days after the last dose (approximately 56 weeks)
Mean Change From Baseline in Lactate Dehydrogenase (LDH) Level	Serum chemistry assessments of LDH were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the treatment period.	Baseline and Day 365
Mean Change From Baseline in Haptoglobin Level	Serum chemistry assessments of haptoglobin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the treatment period.	Baseline and Day 365
Mean Change From Baseline in Hemoglobin (Hb) Level	Hematology assessments of Hb were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the treatment period.	Baseline and Day 365

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score	The FACIT-Fatigue scale is a 13 item Likert scaled instrument where the subject was presented with 13 statements and asked to indicate their response as it applied to the past 7 days. The 5 possible responses were 'Not at all' (0), 'A little bit (1), 'Somewhat' (2), 'Quite a bit' (3) and 'Very much' (4). With 13 statements the total score had a range of 0 to 52. Higher score corresponds to a higher quality of life (QoL).	Baseline and Day 365
Mean Change From Baseline in Absolute Reticulocyte Count (ARC) Level	Hematology assessments of ARC were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the treatment period.	Baseline and Day 365
Mean Change From Baseline in Total Bilirubin Level	Serum chemistry assessments of total bilirubin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the treatment period.	Baseline and Day 365
Mean Number of Red Blood Cell (RBC) Transfusions Per Month	The number of on-study RBC transfusions was monitored throughout the treatment period.	From Day 1 to Day 364
Mean Change From Baseline in Linear Analog Scale Assessment (LASA) Score for QoL	The LASA consists of 3 items, where the respondents were asked to rate their perceived level of functioning. Specific domains included activity level, ability to carry out daily activities, and an item for overall QoL. Their level of functioning was reported on a 0 to 100 scale with 0 indicates "As low as could be" and 100 indicates "As high as could be". The combined score ranged from 0 to 300, with higher scores corresponding to a higher QoL.	Baseline and Day 365
Mean Serum Concentrations of Pegcetacoplan	Serum concentrations of pegcetacoplan at Day 365 are presented.	Day 365
Mean Area Under the Serum Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration at the End of the Study (AUCtotal)	The AUCtotal of pegcetacoplan was estimated using a non-compartmental approach.	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.
Mean Maximum Observed Predose Serum Concentration During the Study (Ctrough,Max,Total)	The Ctrough,max,total of pegcetacoplan was estimated using a non-compartmental approach.	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.

Collaborators and Investigators

• Sponsor: Apellis Pharmaceuticals, Inc.
• Investigators: Study Director: Federico Grossi, MD, PhD, Study Director

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2018
• Primary Completion (Actual): October 22, 2019
• Study Completion (Actual): October 22, 2019

Study Registration Dates

• First Submitted: June 28, 2018
• First Submitted That Met QC Criteria: July 10, 2018
• First Posted (Actual): July 20, 2018

Study Record Updates

• Last Update Posted (Actual): December 22, 2020
• Last Update Submitted That Met QC Criteria: December 21, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Anemia; PNH; Paroxysmal Nocturnal Hemoglobinuria; Complement inhibitor; Hemoglobinuria; C3 inhibitor; Hemolysis; Hematologic diseases; Extravascular hemolysis (EVH); Intravascular hemolysis (IVH)
• Additional Relevant MeSH Terms: Urologic Diseases; Urological Manifestations; Bone Marrow Diseases; Hematologic Diseases; Urination Disorders; Anemia; Proteinuria; Anemia, Hemolytic; Myelodysplastic Syndromes; Hemoglobinuria; Hemoglobinuria, Paroxysmal
• Other Study ID Numbers: APL2-202

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No