Clinical trial NCT04901936: A Study of Pegcetacoplan in Pediatric Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH)
Paroxysmal Hemoglobinuria
Keywords: Paroxysmal Nocturnal Hemoglobinuria
PNH
Pediatric
Adolescent
Apellis
Anemia, Hemolytic
Pegcetacoplan
APL-2
Lead sponsor: Apellis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2021-05-26
Enrollment: 12
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety, effectiveness, and biological activity (how the investigational medication is processed by the body) of pegcetacoplan in 12-17 year-olds (adolescents) who have paroxysmal nocturnal hemoglobinuria (PNH).

Detailed description: This is an open-label study to evaluate pegcetacoplan in people with PNH who are 12-17 years old. The study will consist of a 4-week screening period followed by a 16-week treatment period. Participants switching from a C5 inhibitor will have an additional 4 week run-in period between the screening and treatment periods. At the completion of the study treatment period, participants will either enter a long-term extension period or a 2-month follow-up period.

All eligible study participants will receive pegcetacoplan, administered via subcutaneous infusion twice a week at home. The subcutaneous infusion requires two small needles to be inserted into the fatty layer of tissue under the skin and the investigational medication will flow into the body. Study participants and/or caregivers will be trained on home administration of pegcetacoplan.

Eligibility criteria: Inclusion Criteria:

* Are 12-17 years old at the time of screening
* Weigh at least 20 kg (approx. 44 lbs)
* Have the diagnosis of PNH, confirmed by high-sensitivity flow cytometry (granulocyte or monocyte clone \>10%)
* EITHER:

  * Not being treated with an approved complement inhibitor (eculizumab or ravulizumab) prior to start of pegcetacoplan dosing, AND have hemolytic anemia. Hemolytic anemia is defined as hemoglobin (Hb) less than the lower limit of normal (Hb \< LLN) and LDH \>1.5 times the upper limit of normal (ULN); OR
  * Currently receiving treatment with an approved complement inhibitor (eculizumab or ravulizumab) AND have evidence of ongoing anemia. Ongoing anemia is defined as Hb \< LLN and ARC \> ULN
* Have a platelet count \>75,000/mm3 and an absolute neutrophil count \>1000/mm3

Exclusion Criteria:

* Are an adult, 18 years of age or older, with PNH
* Known or suspected hereditary fructose intolerance (HFI)
* History of hereditary complement deficiency, bone marrow transplant, or meningococcal disease (meningitis, bacteremia or septicemia)
* Females who are pregnant or breastfeeding

Primary outcomes:
measure: Pegcetacoplan serum concentrations over the course of the 16-week treatment period
timeFrame: 16 weeks
measure: Change from baseline to Wk 16 in hemoglobin (Hb)
timeFrame: 16 weeks
measure: Incidence and severity of treatment-emergent adverse events (TEAEs) over the course of the 16-week treatment period, including monitoring bacterial infections
timeFrame: 16 weeks
measure: Change from baseline to wk 16 lactate dehydrogenase (LDH)
timeFrame: 16 weeks
measure: Change from baseline to wk 16 absolute reticulocyte count (ARC)
timeFrame: 16 weeks
Secondary outcomes:
measure: Change from baseline from week 16 to week 52 of C3 deposition on RBC cells
timeFrame: Week 16-52
measure: Incidence of thromboembolic events (major adverse vascular events [MAVE]) over the course of the 16-week treatment period and over 52 weeks of treatment with pegcetacoplan
timeFrame: 52 weeks
measure: Occurrence of breakthrough hemolysis over 16 and 52 weeks of treatment with pegcetacoplan
timeFrame: Week 16-52
measure: Change from baseline to Week 52, and from Week 16 to Week 52 , in Hb
timeFrame: Week 16-52
measure: Change from baseline to Week 16 and to Week 52 in Health-Related Quality of Life (HRQOL) assessments
timeFrame: Week 16-52
measure: Number of packed red blood cell (PRBC) units
timeFrame: Week 16-52
measure: Total units (mL/kg) transfused over 16 and 52 weeks of treatment with pegcetacoplan
timeFrame: Week 16-52
measure: Change from baseline to Week 52, and from Week 16 to Week 52, in LDH
timeFrame: Week 16-52
measure: Change from baseline to Week 52, and from Week 16 to Week 52 ARC
timeFrame: Week 16-52
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Children's Hospital of Atlanta
state: Georgia
city: Prague
country: Czechia
facility: Motol University Hospital
city: Paris
country: France
facility: Robert-Debré Hospital Paris
city: Ampang
country: Malaysia
facility: Hospital Ampang
city: Nijmegen
country: Netherlands
facility: Radboud University Hospital Nijmegen
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Belgrade
country: Serbia
facility: University Children's Hospital
city: Barcelona
country: Spain
facility: University Hospital Vall d'Hebron
city: Madrid
country: Spain
facility: University Hospital 12 de Octubre
city: Bangkok
country: Thailand
facility: Phramongkutklao Hospital and College of Medicine
city: Chiang Mai
country: Thailand
facility: Maharaj Nakorn Chiang Mai hospital
city: London
country: United Kingdom
facility: St. Mary's Hospital
Study officials:
References: