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

Phase 1

Completed

• Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH)
• Interventions: Drug: Pegcetacoplan

• Registration Number: NCT02264639
• Lead Sponsor: Apellis Pharmaceuticals, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-10-08
• Study First Submitted QC: 2014-10-10
• Study First Posted: 2014-10-15
• Study Start: 2015-02-23
• Primary Completion: 2018-10-22
• Study Completion: 2018-10-22
• Results First Submitted: 2020-07-31
• Status Verified: 2020-12
• Results First Submitted QC: 2020-12-14
• Last Update Submitted: 2020-12-14
• Results First Posted: 2021-01-08
• Last Update Posted: 2021-01-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 9

Inclusion Criteria

• 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

Exclusion Criteria

• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 4	Pegcetacoplan	Repeated Dose 270 mg/day
Cohort 1	Pegcetacoplan	First Dose 25mg, Repeated Dose 5 mg/day
Cohort 2	Pegcetacoplan	First Dose 50 mg, Repeated Dose 30 mg/day
Cohort 3	Pegcetacoplan	Repeated Dose 180 mg/day

Primary Outcome Measures

Name	Time	Method
Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Including by Severity, During Single-dose Phase	From single dose of study drug (Day 1) up to 30 days	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.
Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase	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).	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.
Area Under the Curve (AUC) From Time 0 to the Last Measurable Concentration (AUC0-t) Over the Multiple Dosing Phase for Cohort 4	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.	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.
Maximum Pre-dose Serum Concentration (Ctrough,Max) Over the Multiple Dosing Phase for Cohort 4	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.	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.

Trial Locations

Locations (7)

University of Southern California Norris Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States

Lakes Research; 🇺🇸 Miami Lakes, Florida, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

John Hopkins Hospital; 🇺🇸 Baltimore, Maryland, United States

University of Lousiville; 🇺🇸 Louisville, Kentucky, United States

Cure 4 The Kids Foundation; 🇺🇸 Las Vegas, Nevada, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States