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Completed

NCT Number: NCT03593200

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

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.

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Acibadem City Clinic MHAT Tokuda EAD Sofia, Sofia, Bulgaria

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Pegcetacoplan

Drug

Complement (C3) Inhibitor

Other names: APL-2

Primary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

Secondary outcomes

  1. 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).

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Mean Serum Concentrations of Pegcetacoplan

    Time frame: Day 365

    Serum concentrations of pegcetacoplan at Day 365 are presented.

  7. 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.

  8. 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.

Sponsors and collaborators

Lead sponsor

Apellis Pharmaceuticals, Inc.

Industry

Registry information

Official study 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).

Important dates

Study start
2018
Primary completion
2019
Study completion
2019
First posted
Jul 20, 2018
Registry last updated
Dec 22, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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