Pilot Study to Assess Safety, Preliminary Efficacy and Pharmacokinetics of S.C. Pegcetacoplan (APL-2) in PNH Subjects.

NCT02588833 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: APL2-CP-PNH-204
• Study Type: interventional
• Target: 23
• Locations: 4 countries
• Sites: 7

Brief Summary

The objectives of the study are to assess the safety, tolerability, preliminary efficacy and PK of multiple subcutaneous (SC) doses of pegcetacoplan 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 pegcetacoplan when administered to PNH patients.

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Keywords

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

Outcome Measures

Primary Outcomes (7)

• Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity

  TEAEs were defined as adverse events (AEs) that occurred after dosing on Day 1 and up to 30 days after the last dose of study drug. A treatment-related TEAE is defined as a TEAE with a relationship to study drug of probably, possibly, unlikely, or unrelated. A serious adverse event (SAE) is defined as any AE that resulted in death; was life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant incapacity or substantial disruption of ability to conduct normal life functions; was a congenital anomaly or birth defect. TEAEs were graded according to 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 first dose of study drug (Day 1) up to 30 days after the last dose of study drug, up to approximately 563 days.

• Mean Change From Baseline in Lactate Dehydrogenase (LDH) at Day 365

  Serum chemistry assessments of LDH were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. LDH results were summarized for Cohort 2 only.

  Baseline (Day 1) and Day 365.

• Mean Percentage Change From Baseline in LDH at Day 365

  Serum chemistry assessments of LDH were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. LDH results were summarized for Cohort 2 only.

  Baseline (Day 1) and Day 365.

• Mean Change From Baseline in Haptoglobin at Day 365

  Serum chemistry assessments of haptoglobin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. Haptoglobin results were summarized for Cohort 2 only.

  Baseline (Day 1) and Day 365.

• Mean Percentage Change From Baseline in Haptoglobin at Day 365

  Serum chemistry assessments of haptoglobin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. Haptoglobin results were summarized for Cohort 2 only.

  Baseline (Day 1) and Day 365.

• Mean Change From Baseline in Hemoglobin at Day 365

  Hematology assessments of hemoglobin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. Hemoglobin results were summarized for Cohort 2 only.

  Baseline (Day 1) and Day 365.

• Mean Percentage Change From Baseline in Hemoglobin at Day 365

  Hematology assessments of hemoglobin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. Hemoglobin results were summarized for Cohort 2 only.

  Baseline (Day 1) and Day 365.

Secondary Outcomes (6)

• Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Day 365

  Baseline (Day 1) and Day 365.

• Mean Change From Baseline in Absolute Reticulocyte Count (ARC) at Day 365

  Baseline (Day 1) and Day 365.

• Mean Percentage Change From Baseline in ARC at Day 365

  Baseline (Day 1) and Day 365.

• Mean Change From Baseline in Total Bilirubin at Day 365

  Baseline (Day 1) and Day 365.

• Mean Percentage Change From Baseline in Total Bilirubin at Day 365

  Baseline (Day 1) and Day 365.

Study Arms (2)

Cohort 1

EXPERIMENTAL

180 mg pegcetacoplan/day

Drug: Pegcetacoplan

Cohort 2

EXPERIMENTAL

270 mg pegcetacoplan/day

Drug: Pegcetacoplan

Interventions

Pegcetacoplan DRUG

Complement (C3) Inhibitor

Also known as: APL-2

Cohort 1; Cohort 2

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Apellis Pharmaceuticals, Inc.: lead

Study Sites (7)

Prince of Wales Hospital

Hong Kong, Hong Kong

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Hospital Ampang

Ampang, Selangor, 68000, Malaysia

Location

Waikato Hospital

Hamilton, Waikato Region, 3240, New Zealand

Location

Ramathibodi Hospital

Bangkok, 10400, Thailand

Location

Siriraj hospital

Bangkok, 10700, Thailand

Location

Phramongkutklao Hospital

Bangkok, Thailand

Location

Related Publications (2)

• Panse J, Daguindau N, Okuyama S, Peffault de Latour R, Schafhausen P, Straetmans N, Al-Adhami M, Persson E, Wong RSM. Improvements in hematologic markers and decreases in fatigue with pegcetacoplan for patients with paroxysmal nocturnal hemoglobinuria and mild or moderate anemia (hemoglobin >/=10 g/dL) who had received eculizumab or were naive to complement inhibitors. PLoS One. 2024 Jul 29;19(7):e0306407. doi: 10.1371/journal.pone.0306407. eCollection 2024.

  PMID: 39079163 DERIVED

• 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

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

  Apellis Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2015
• First Posted: October 28, 2015
• Study Start: December 1, 2015
• Primary Completion: August 26, 2019
• Study Completion: August 26, 2019
• Last Updated: January 11, 2021
• Results First Posted: January 11, 2021

Record last verified: 2020-12

Locations

MY (1); NZ (1); TH (3); HK (2)