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

• ClinicalTrials.gov Identifier: NCT03593200
• Recruitment Status: Completed
• First Posted: July 20, 2018
• Results First Posted: December 22, 2020
• Last Update Posted: December 22, 2020
• Sponsor: Apellis Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Apellis Pharmaceuticals, Inc.

Tracking Information

• First Submitted Date: June 28, 2018
• First Posted Date: July 20, 2018
• Results First Submitted Date: August 4, 2020
• Results First Posted Date: December 22, 2020
• Last Update Posted Date: December 22, 2020
• Actual Study Start Date: August 16, 2018
• Actual Primary Completion Date: October 22, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 4, 2020)

• Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity [ Time Frame: From Day 1 to 30 days after the last dose (approximately 56 weeks) ]
  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.
• Mean Change From Baseline in Lactate Dehydrogenase (LDH) Level [ Time Frame: Baseline and 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 treatment period.
• Mean Change From Baseline in Haptoglobin Level [ Time Frame: Baseline and 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 treatment period.
• Mean Change From Baseline in Hemoglobin (Hb) Level [ Time Frame: Baseline and Day 365 ]
  Hematology assessments of Hb were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the treatment period.

Original Primary Outcome Measures (submitted: July 10, 2018)

• 1.Number of treatment emergent adverse events (TEAEs) following administration of multiple doses of SC APL-2. Severity of treatment emergent adverse events (TEAEs) following administration of multiple doses of SC APL-2. [ Time Frame: Change from baseline up to week 36 ]
• 2. LDH (U/L) [ Time Frame: Change from baseline up to week 32 ]
• 3. Haptoglobin (mg/dL) & Hemoglobin (g/dl) [ Time Frame: Change from baseline up to week 32 ]

Current Secondary Outcome Measures (submitted: September 30, 2020)

• Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score [ Time Frame: Baseline and Day 365 ]
  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).
• Mean Change From Baseline in Absolute Reticulocyte Count (ARC) Level [ Time Frame: Baseline and Day 365 ]
  Hematology assessments of ARC were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the treatment period.
• Mean Change From Baseline in Total Bilirubin Level [ Time Frame: Baseline and Day 365 ]
  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.
• Mean Number of Red Blood Cell (RBC) Transfusions Per Month [ Time Frame: From Day 1 to Day 364 ]
  The number of on-study RBC transfusions was monitored throughout the treatment period.
• Mean Change From Baseline in Linear Analog Scale Assessment (LASA) Score for QoL [ Time Frame: Baseline and Day 365 ]
  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.
• Mean Serum Concentrations of Pegcetacoplan [ Time Frame: Day 365 ]
  Serum concentrations of pegcetacoplan at Day 365 are presented.
• Mean Area Under the Serum Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration at the End of the Study (AUCtotal) [ Time Frame: 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. ]
  The AUCtotal of pegcetacoplan was estimated using a non-compartmental approach.
• Mean Maximum Observed Predose Serum Concentration During the Study (Ctrough,Max,Total) [ Time Frame: 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. ]
  The Ctrough,max,total of pegcetacoplan was estimated using a non-compartmental approach.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase IIa Study to Assess the Safety, Efficacy, and Pharmacokinetics of Subcutaneously Administered Pegcetacoplan (APL-2) in Subjects With PNH
• Official Title: 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).
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: PNH

Intervention

Drug: Pegcetacoplan

Complement (C3) Inhibitor

Other Name: APL-2

Study Arms

Experimental: Experimental: Cohort 1

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

Intervention: Drug: Pegcetacoplan

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 18, 2019): 4
• Original Estimated Enrollment (submitted: July 10, 2018): 20
• Actual Study Completion Date: October 22, 2019
• Actual Primary Completion Date: October 22, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Bulgaria, Serbia
• Removed Location Countries: Greece, Poland, Romania

Administrative Information

• NCT Number: NCT03593200
• Other Study ID Numbers: APL2-202
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Apellis Pharmaceuticals, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Apellis Pharmaceuticals, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Federico Grossi, MD, PhD; Study Director

• PRS Account: Apellis Pharmaceuticals, Inc.
• Verification Date: December 2020