A Phase I Study to Assess the Safety of Pegcetacoplan (APL-2) as an Add-On to Standard of Care in Subjects With PNH

NCT02264639 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: APL-CP0514
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 7

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.

Conditions

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Keywords

PNH; Paroxysmal Nocturnal Hemoglobinuria; Complement inhibitor; Anemia; Hemoglobinuria; 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, During Single-dose Phase

  TEAEs were defined as AEs that developed or worsened after first dose of study drug (Day 1), and up to 30 days after last dose of study drug. The Investigator assessed AEs for severity and relatedness to study drug. AEs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE, v4.03) based on: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death related to AE.

  From single dose of study drug (Day 1) up to 30 days

• Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase

  TEAEs were defined as AEs that developed or worsened after first dose of study drug (Day 1), and up to 30 days after last dose of study drug. The Investigator assessed AEs for severity and relatedness to study drug. AEs were graded according to CTCAE, 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 up to 30 days after last dose of study drug (Cohorts 1-3: up to 58 days; Cohort 4: up to 759 days).

• Area Under the Curve (AUC) From Time 0 to the Last Measurable Concentration (AUC0-t) Over the Multiple Dosing Phase for Cohort 4

  Assessment of AUC0-t of pegcetacoplan over the multiple dosing phase, estimated using a non-compartmental approach and calculated by the linear-log trapezoidal method. Pegcetacoplan pharmacokinetic (PK) parameters were summarized for Cohort 4 only.

  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.

• Maximum Pre-dose Serum Concentration (Ctrough,Max) Over the Multiple Dosing Phase for Cohort 4

  Assessment of Ctrough,max of pegcetacoplan over the multiple dosing phase, estimated using a non-compartmental approach. Pegcetacoplan PK parameters were summarized for Cohort 4 only. Ctrough,max was calculated for both 270 mg/day and 360 mg/day where subjects received both doses. Note: 1 subject in Cohort 4 who was receiving 360 mg/day was granted Sponsor and institutional review board approval to increase the dose further to the equivalent of 440 mg/day and Ctrough,max is also reported for this dose.

  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.

Study Arms (4)

Cohort 1

EXPERIMENTAL

First Dose 25mg, Repeated Dose 5 mg/day

Drug: Pegcetacoplan

Cohort 2

EXPERIMENTAL

First Dose 50 mg, Repeated Dose 30 mg/day

Drug: Pegcetacoplan

Cohort 3

EXPERIMENTAL

Repeated Dose 180 mg/day

Drug: Pegcetacoplan

Cohort 4

EXPERIMENTAL

Repeated Dose 270 mg/day

Drug: Pegcetacoplan

Interventions

Pegcetacoplan DRUG

Complement (C3) Inhibitor

Also known as: APL-2

Cohort 1; Cohort 2; Cohort 3; Cohort 4

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 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Apellis Pharmaceuticals, Inc.: lead

Study Sites (7)

University of Southern California Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Lakes Research

Miami Lakes, Florida, 33014, United States

Location

University of Lousiville

Louisville, Kentucky, 40202, United States

Location

John Hopkins Hospital

Baltimore, Maryland, 21231, United States

Location

Cure 4 The Kids Foundation

Las Vegas, Nevada, 89135, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

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

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: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2014
• First Posted: October 15, 2014
• Study Start: February 23, 2015
• Primary Completion: October 22, 2018
• Study Completion: October 22, 2018
• Last Updated: January 8, 2021
• Results First Posted: January 8, 2021

Record last verified: 2020-12

Locations

US (7)