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

NCT03593200 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: APL2-202
• Study Type: interventional
• Target: 4
• Locations: 2 countries
• Sites: 3

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.

Conditions

PNH

Keywords

PNH; Paroxysmal Nocturnal Hemoglobinuria; Complement inhibitor; Anemia; Hemoglobinuria; Hemolysis; Hematologic diseases; Extravascular hemolysis (EVH); Intravascular hemolysis (IVH); C3 inhibitor

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (8)

• Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score

  Baseline and Day 365

• Mean Change From Baseline in Absolute Reticulocyte Count (ARC) Level

  Baseline and Day 365

• Mean Change From Baseline in Total Bilirubin Level

  Baseline and Day 365

• Mean Number of Red Blood Cell (RBC) Transfusions Per Month

  From Day 1 to Day 364

• Mean Change From Baseline in Linear Analog Scale Assessment (LASA) Score for QoL

  Baseline and Day 365

Study Arms (1)

Experimental: Cohort 1

EXPERIMENTAL

270 mg/day (up to 360 mg/day from Day 29) from Day 1 to Day 364\*

Drug: Pegcetacoplan

Interventions

Pegcetacoplan DRUG

Complement (C3) Inhibitor

Also known as: APL-2

Experimental: Cohort 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Apellis Pharmaceuticals, Inc.: lead

Study Sites (3)

Acibadem City Clinic MHAT Tokuda EAD Sofia

Sofia, Bulgaria

Location

Specialized Hospital for Active Treatment of Hematologic Diseases EAD, Sofia

Sofia, Bulgaria

Location

Klinički centar Srbije

Belgrade, Serbia

Location

Related Publications (1)

• 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.

  PMID: 35869170 DERIVED

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal; Anemia; Hemoglobinuria; Hemolysis; Hematologic Diseases

Interventions

pegcetacoplan

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases; Proteinuria; Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pathologic Processes

Limitations and Caveats

Given the small sample size, no conclusions should be drawn from the results summarized and reported as descriptive statistics in Outcome Measures 9-12.

Results Point of Contact

• Title: Apellis Clinical Trial Information Line
• Organization: Apellis Pharmaceuticals, Inc

clinicaltrials@apellis.com

1-833-284-6361

Study Officials

• Federico Grossi, MD, PhD

  Study Director

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2018
• First Posted: July 20, 2018
• Study Start: August 16, 2018
• Primary Completion: October 22, 2019
• Study Completion: October 22, 2019
• Last Updated: December 22, 2020
• Results First Posted: December 22, 2020

Record last verified: 2020-12

Locations

SE (1); BU (2)