Evaluation of Safety, Pharmacokinetics, and Biologic Activity of Pegcetacoplan in Adolescents with Paroxysmal Nocturnal Hemoglobinuria: A Phase 2, Open-Label, Single-Arm Study
- Trial ID
- 2024-516350-22-00
- Protocol
- APL2-PNH-209
- Sponsor
- Apellis Pharmaceuticals Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to define the **pharmacokinetics** of pegcetacoplan in adolescents with Paroxysmal Nocturnal Hemoglobinuria (PNH). Additionally, the study aims to evaluate the efficacy of pegcetacoplan based on hemoglobin (Hb) level, lactate dehydrogenase (LDH) level, and absolute reticulocyte count (ARC). The safety of pegcetacoplan will also be assessed by measuring the incidence and severity of treatment-emergent adverse events (TEAEs), including bacterial infections. Understanding the pharmacokinetics and safety profile of pegcetacoplan in this population is crucial for optimizing treatment regimens and improving clinical outcomes in pediatric patients with PNH.
Secondary objectives include: - Assessing the pharmacodynamics and biological activity of pegcetacoplan by examining effects on complement levels, C3 deposition on red blood cells (RBCs), and clonal distribution of PNH RBCs. - Evaluating the efficacy of pegcetacoplan by analyzing its impact on transfusion requirements and episodes of breakthrough hemolysis. - Assessing the effect of pegcetacoplan on health-related quality of life (HRQOL) using the FACIT-Fatigue and PedsQL General Well-Being Scale. - Evaluating the long-term safety and efficacy of pegcetacoplan. - Assessing the safety of pegcetacoplan by monitoring the occurrence of thromboembolic events.
Participants
The clinical trial involves a total of **8 participants** diagnosed with **Paroxysmal Nocturnal Hemoglobinuria** (PNH). The study population comprises adolescents aged between 12 and 17 years, inclusive, at the time of study entry. Both male and female subjects are included, with specific considerations for females of childbearing potential, who must have a negative pregnancy test and agree to use contraception. Participants are required to have a confirmed diagnosis of PNH through high-sensitivity flow cytometry. The trial includes both naïve patients, who are not currently receiving complement inhibitors, and switch patients, who are on a stable dose of such inhibitors. Key health criteria include a platelet count greater than 75,000/mm³, an absolute neutrophil count over 1000/mm³, and a body mass index below the 95th percentile for their age. Participants must weigh at least 20 kg and have received specific vaccinations or agree to receive them shortly after starting treatment. The trial population was selected based on these criteria to ensure the safety and efficacy of pegcetacoplan in this vulnerable group.
Plans and Procedures
The clinical trial is designed as an open-label, single-arm, Phase 2 study to evaluate the safety, pharmacokinetics, and biologic activity of **pegcetacoplan** in pediatric patients with **Paroxysmal Nocturnal Hemoglobinuria** (PNH). The trial will involve a 16-week treatment period, during which participants will receive **pegcetacoplan** via subcutaneous use. The primary objectives include defining the pharmacokinetics of **pegcetacoplan** in adolescents, evaluating its efficacy based on hemoglobin (Hb) level, lactate dehydrogenase (LDH) level, and absolute reticulocyte count (ARC), and assessing safety through the incidence and severity of treatment-emergent adverse events (TEAEs), including bacterial infections.
Participants will be involved in the study for a total duration of 16 weeks, with the possibility of extending to 52 weeks for secondary endpoints. The study will commence with a screening visit to confirm eligibility, which includes criteria such as age between 12 and 17 years, a confirmed diagnosis of PNH, and specific laboratory parameters. Following the screening, eligible participants will begin treatment on Day 1, with subsequent follow-up visits scheduled to monitor safety, efficacy, and pharmacokinetics. The end-of-study visit will occur at the conclusion of the 16-week treatment period, with additional assessments for those continuing to 52 weeks.
Participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with study procedures, or if the investigator deems it necessary for their safety. The study aims to provide comprehensive data on the pharmacokinetics and safety profile of **pegcetacoplan** in the pediatric population, contributing to the understanding of its therapeutic potential in managing PNH. The trial is expected to conclude by August 2025, with recruitment having started in October 2020.
Treatment
The clinical trial involves the administration of **ASPAVELI**, a solution for infusion containing the active substance **pegcetacoplan**. Pegcetacoplan is a protein-based therapeutic agent, specifically classified under the ATC code L04AJ03. The pharmaceutical form of ASPAVELI is a solution for infusion, and it is administered via **subcutaneous use**. The maximum daily dose of ASPAVELI is 1080 mg, with a total maximum dose of 43200 mg over a treatment period of 16 weeks. The product is specifically packaged and labeled for use in this study, ensuring compliance with trial protocols. The administration schedule is designed to maintain consistent therapeutic levels, and participant compliance is monitored throughout the trial duration.
In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on evaluating the safety, pharmacokinetics, and biological activity of pegcetacoplan in pediatric patients diagnosed with **paroxysmal nocturnal hemoglobinuria**. The trial is open-label and single-arm, allowing for direct observation of the effects of the experimental medication without the influence of additional treatments. Compliance with dosing schedules is critical, and adherence is monitored to ensure the integrity of the trial data.
Efficacy
The efficacy of **pegcetacoplan** in the clinical trial will be assessed through several primary and secondary endpoints. The primary efficacy endpoints include the change from baseline to Week 16 in hemoglobin (Hb) level, lactate dehydrogenase (LDH) level, and absolute reticulocyte count (ARC). These parameters will be measured to evaluate the pharmacodynamics and efficacy of the treatment over the 16-week period. The safety of pegcetacoplan will also be monitored by assessing the incidence and severity of treatment-emergent adverse events (TEAEs), including bacterial infections, throughout the treatment duration.
Secondary efficacy endpoints will further explore the pharmacodynamics by measuring changes from baseline to Week 16 and Week 52 in complement levels, such as total complement hemolytic activity (CH50), alternative complement pathway hemolytic activity (AH50), and C3 level. Additionally, the study will assess C3 deposition on red blood cells (RBCs) and the clonal distribution of paroxysmal nocturnal hemoglobinuria (PNH) RBCs. The number of transfusions, number of packed RBC units, and total units transfused over 16 and 52 weeks will also be recorded. The occurrence of breakthrough hemolysis and changes in health-related quality of life assessments, including FACIT-Fatigue and PedsQL General Well-Being Scale, will be evaluated from baseline to Week 16 and Week 52.
Data collection will occur at specified timepoints, with primary endpoints assessed at Week 16 and secondary endpoints extending to Week 52. The analysis will involve comparing baseline values to those obtained at these timepoints to determine the efficacy of pegcetacoplan in treating pediatric patients with paroxysmal nocturnal hemoglobinuria.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Between the ages of 12 and 17, inclusive, at time of study entry
- A diagnosis of PNH, confirmed by high-sensitivity flow cytometry (granulocyte or monocyte clone >10%)
- Be either a naïve patient or a switch patient, as defined below. a. A naïve patient must: i. Not be currently receiving an approved complement inhibitor, and must not have received a complement inhibitor within at least 5 half-lives of that drug prior to starting pegcetacoplan ii. Have evidence of a hemolytic anemia based on a hemoglobin less than the lower limit of the normal range (LLN), and LDH >1.5 × ULN. b. A switch patient must: i. Be currently receiving treatment with an approved complement inhibitor, and the dose of that inhibitor must have been stable for at least 5 half-lives of that drug ii. Have evidence of anemia based on a hemoglobin less than the LLN. iii. Have ARC > ULN
- Platelet count >75,000/mm3
- Absolute neutrophil count >1000/mm3
- Weigh at least 20 kg
- Have a body mass index (BMI) that is less than the 95th percentile for their age
- Either not receiving the following medications, or on a stable regimen for at least the minimum time period indicated below, prior to the first screening visit, with no anticipated changes to the regimen over the course of the study: a. Erythropoietin: 8 weeks b. Systemic corticosteroids: 4 weeks c. Immunosuppressants (other than steroids): 8 weeks d. Vitamin K antagonists (eg, warfarin): 4 weeks, with a stable international normalized ratio (INR) over that period e. Iron supplements, vitamin B12, or folic acid: 4 weeks f. Low-molecular weight heparin or direct oral anticoagulants (DOACs): 4 weeks
- Have received vaccinations against Neisseria meningitidis (types A, C, W, Y, and B), Streptococcus pneumoniae, and Haemophilus influenzae (type B) prior to dosing on Day 1, or agree to receive vaccinations within 14 days after starting treatment with pegcetacoplan. Vaccination is mandatory, unless there is documented evidence of titers within acceptable local limits, or documented evidence of nonresponse to vaccination based on titers. Subjects receiving vaccinations after starting pegcetacoplan must be willing to take prophylactic antibiotics from the first day of treatment with pegcetacoplan until at least 2 weeks after vaccination as described in Section 8.2.1
- Female subjects of childbearing potential must have a negative blood pregnancy test at screening (and negative urine pregnancy test on Day 1) and must agree to practice abstinence or to use another protocol-defined method of contraception, as described in Section 10.3.5.1, from screening through at least 90 days after receiving the last dose of pegcetacoplan
- Male subjects who have reached sexual maturity must agree to practice abstinence or to use another protocol-defined method of contraception, as described in Section 10.3.5.1, and agree to refrain from donating semen from screening through at least 90 days after receiving the last dose of pegcetacoplan
- Willing and able to self-administer pegcetacoplan or has a caregiver who is willing and able to do so
- The subject or their legally authorized representative must be willing and able to provide written informed consent as described in Section 12.1.2, including compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Where appropriate, the subject must also give their assent to participation in the study
Exclusion Criteria
- Known or suspected hereditary fructose intolerance (HFI)
- Active bacterial infection that has not resolved within at least 1 week before the first dose of pegcetacoplan
- Hereditary complement deficiency
- History of bone marrow transplantation
- History or presence of hypersensitivity or idiosyncratic reaction to compounds related to the formulation or SC administration of pegcetacoplan
- Participation in another investigational drug trial or exposure to another investigational agent, device, or procedure within 30 days or 5 half-lives (whichever is longer) from the last dose of investigational agent prior to screening period
- Planning to become pregnant during study participation, or currently breastfeeding
- History of meningococcal disease
- Inability to cooperate, or any condition that, in the opinion of the investigator makes the subject inappropriate for the study or could confound the outcome of the study
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 The Netherlands | Recruiting | 31 Jan 2028 | — |
 Spain | Recruiting | 31 Jan 2028 | 2 |
| Netherlands | — | — | 2 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
ASPAVELI 1 080 mg solution for infusion | Test | SOLUTION FOR INFUSION | SUBCUTANEOUS USE | 1080 | 16 | PRD9373394 |
ASPAVELI 1 080 mg solution for infusion | Test | SOLUTION FOR INFUSION | SUBCUTANEOUS USE | 1080 | 16 | PRD9373392 |
ASPAVELI 1 080 mg solution for infusion | Test | SOLUTION FOR INFUSION | SUBCUTANEOUS USE | 1080 | 16 | PRD9373388 |
ASPAVELI 1 080 mg solution for infusion | Test | SOLUTION FOR INFUSION | SUBCUTANEOUS USE | 1080 | 16 | PRD9373393 |