pegcetacoplan for Paroxysmal nocturnal hemoglobinuria

Inclusion criteria

• {"criterion_text":"- Between the ages of 12 and 17, inclusive, at time of study entry"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Willing and able to self-administer pegcetacoplan or has a caregiver who is willing and able to do so"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- A diagnosis of PNH, confirmed by high-sensitivity flow cytometry (granulocyte or monocyte clone >10%)"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Platelet count >75,000/mm3"}
• {"criterion_text":"- Absolute neutrophil count >1000/mm3"}
• {"criterion_text":"- Weigh at least 20 kg"}
• {"criterion_text":"- Have a body mass index (BMI) that is less than the 95th percentile for their age"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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"}

Exclusion criteria

• {"criterion_text":"- Known or suspected hereditary fructose intolerance (HFI)"}
• {"criterion_text":"- Active bacterial infection that has not resolved within at least 1 week before the first dose of pegcetacoplan"}
• {"criterion_text":"- Hereditary complement deficiency"}
• {"criterion_text":"- History of bone marrow transplantation"}
• {"criterion_text":"- History or presence of hypersensitivity or idiosyncratic reaction to compounds related to the formulation or SC administration of pegcetacoplan"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Planning to become pregnant during study participation, or currently breastfeeding"}
• {"criterion_text":"- History of meningococcal disease"}
• {"criterion_text":"- 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"}

Primary endpoints

• {"endpoint_text":"- Pharmacokinetics: Pegcetacoplan concentrations and PK parameters over the course of the 16-week treatment period","definition_or_measurement_approach":"Measurement of pegcetacoplan plasma concentrations and derived PK parameters collected over the 16-week treatment period"}
• {"endpoint_text":"- Efficacy and Pharmacodynamics: Change from baseline to Week 16 in Hb level","definition_or_measurement_approach":"Change in hemoglobin concentration from baseline to Week 16"}
• {"endpoint_text":"- Efficacy and Pharmacodynamics: Change from baseline to Week 16 in LDH level","definition_or_measurement_approach":"Change in lactate dehydrogenase (LDH) level from baseline to Week 16"}
• {"endpoint_text":"- Efficacy and Pharmacodynamics: Change from baseline to Week 16 in ARC","definition_or_measurement_approach":"Change in absolute reticulocyte count (ARC) from baseline to Week 16"}
• {"endpoint_text":"- Safety: Incidence and severity of TEAEs over the course of the 16-week treatment period, including bacterial infections","definition_or_measurement_approach":"Recording and classification of treatment-emergent adverse events (TEAEs) including incidence and severity during the 16-week treatment period; specific monitoring for bacterial infections"}

Secondary endpoints

• {"endpoint_text":"- Efficacy and Pharmacodynamics: Change from baseline to Week 16 and Week 52 in: − Complement levels (eg, total complement hemolytic activity [CH50], alternative complement pathway hemolytic activity [AH50], and C3 level) − C3 deposition on RBCs − Clonal distribution of PNH RBCs","definition_or_measurement_approach":"Measurement of complement assays (CH50, AH50, C3), assays for C3 deposition on red blood cells, and assessment of clonal distribution of PNH red blood cells at baseline, Week 16, and Week 52"}
• {"endpoint_text":"- Efficacy and Pharmacodynamics: Number of transfusions, number of packed RBC units, and total units (mL/kg) transfused over 16 and 52 weeks of treatment with pegcetacoplan","definition_or_measurement_approach":"Counting transfusion events, units transfused, and calculating total mL/kg transfused over 16- and 52-week periods"}
• {"endpoint_text":"- Efficacy and Pharmacodynamics: Occurrence of breakthrough hemolysis over 16 and 52 weeks of treatment with pegcetacoplan","definition_or_measurement_approach":"Recording episodes meeting protocol-defined criteria for breakthrough hemolysis during 16- and 52-week timeframes"}
• {"endpoint_text":"- Efficacy and Pharmacodynamics: Change from baseline to Week 52, and from Week 16 to Week 52, in hemoglobin, LDH, and ARC","definition_or_measurement_approach":"Change in hemoglobin, LDH, and ARC between baseline and Week 52 and between Week 16 and Week 52"}
• {"endpoint_text":"- Efficacy and Pharmacodynamics: Change from baseline to Week 16 and to Week 52 in Health-Related Quality of Life assessments (FACIT-Fatigue and PedsQL General Well-Being Scale)","definition_or_measurement_approach":"Assessment of HRQOL using FACIT-Fatigue and PedsQL General Well-Being Scale at baseline, Week 16 and Week 52 and calculation of change scores"}
• {"endpoint_text":"- Safety: 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","definition_or_measurement_approach":"Recording incidence of thromboembolic events/MAVE during 16-week treatment period and through 52 weeks"}

Netherlands

Earliest CTIS Part Ii Submission Date

02-09-2024

Latest Decision Or Authorization Date

02-03-2026

Processing Time Days

546

Number Of Sites

1

Number Of Participants

2

Spain

Earliest CTIS Part Ii Submission Date

02-09-2024

Latest Decision Or Authorization Date

05-03-2026

Processing Time Days

549

Number Of Sites

2

Number Of Participants

2

Primary sponsor

Full Name

Apellis Pharmaceuticals Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

4g Clinical LLC

Responsibilities

IVRS treatment randomization

Name

Worldwide Clinical Trials Holdings Inc.

Third parties

• {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"IVRS treatment randomization","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Worldwide Clinical Trials Holdings Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medpace Reference Laboratories LLC","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"World Courier (U.K.) Limited","duties_or_roles":"Direct shipments to patients","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Q Squared Solutions LLC","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Belgium","full_name":"MEDPACE LABORATORIES","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"Clinigen Clinical Supplies Management GmbH","duties_or_roles":"Non-IMP Depot for Concomitant Medications (vaccines, antibiotics)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Gray Consulting Inc.","duties_or_roles":"Patient travel services (coordinating site travel for cars, flights, hotels, reimbursement)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Q Squared Solutions LLC","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"National Jewish Health","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Hungary","full_name":"Precision for Medicine (HU) Kft.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioagilytix Labs LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Professional Case Management Clinical Trials LLC","duties_or_roles":"Home nursing","organisation_type":"Laboratory/Research/Testing facility"}