An Open-label, Nonrandomized, Multicenter Extension Study to Evaluate the Long-term Safety and Efficacy of Pegcetacoplan in the Treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH)
- Conditions
- Paroxysmal Nocturnal HemoglobinuriaMedDRA version: 21.1Level: LLTClassification code 10055629Term: Paroxysmal nocturnal hemoglobinuriaSystem Organ Class: 100000004857Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2019-001106-23-BG
- Lead Sponsor
- Apellis Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 160
1. Subjects at least 18 years of age with PNH who have participated in an antecedent pegcetacoplan clinical trial. Subjects who received treatment with pegcetacoplan must have experienced clinical benefit and adequate tolerability in the opinion of the investigator.
Note: Subjects with PNH who completed an antecedent pegcetacoplan clinical trial without receiving pegcetacoplan (or without receiving pegcetacoplan for long enough to demonstrate clinical benefit) may be enrolled in this study if, in the opinion of the Investigator, the subject is expected to demonstrate clinical benefit upon the initiation or continuation of pegcetacoplan therapy.
2. Vaccination against Neisseria meningitidis types A, C, W, Y and B, Streptococcus pneumoniae and Haemophilus influenzae Type B (Hib) either within 2 years prior to Day 1 dosing of this study, or within 14 days after starting treatment with pegcetacoplan. Vaccination is mandatory unless documented evidence exists that subjects are nonresponders to vaccination as evidenced by titers or display titer levels within acceptable local limits. Immunization status checks will be performed to determine whether subjects require primary or booster vaccinations.
3. Willing and able to give written informed consent.
4. Willing and able to self-administer pegcetacoplan (administration by a caregiver will be allowed).
5. Women of childbearing potential, defined as any females who have experienced menarche and who are NOT permanently sterile or postmenopausal, must have a negative pregnancy test and must agree to continue to use an approved method of contraception for the duration of the study and 90 days after their last dose of study drug. Note: Postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause.
6. Males must agree to continue to use an approved method of contraception and must agree to refrain from donating sperm for the duration of the study and 90 days after their last dose of study drug.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 136
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 24
1. Subjects who have withdrawn from a pegcetacoplan clinical study and/or subjects who met study drug discontinuation criteria during a pegcetacoplan clinical study.
2. Any condition that could increase the subject’s risk by participating in the study.
3. Any comorbidity or condition (such as malignancy) that, in the opinion of the investigator, could put the subject at increased risk or potentially confound the study data.
4. History or presence of hypersensitivity or idiosyncratic reaction to compounds related to the investigational product or SC administration.
5. Acute or active hepatitis B, hepatitis C, or HIV infection.
6. Hereditary complement deficiency.
7. History of bone marrow transplant.
8. Concurrent severe aplastic anemia (defined by bone marrow cellularity <25% [or 25% to 50% if less than 30% of residual cells are hematopoietic] and at least 2 of the following values: peripheral blood absolute neutrophil count <500/µL [<0.5 × 109/L], peripheral blood platelet count <20,000/µL, peripheral blood reticulocyte count <20,000/µL).
9. History of meningococcal disease.
10. Concomitant treatment with any complement inhibitor (eg, eculizumab, ravulizumab).
11. Pregnancy, breastfeeding, or positive pregnancy test.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The objectives of this study are to:<br>1. Establish the long-term safety of pegcetacoplan in PNH subjects<br>2. Establish the long-term efficacy of pegcetacoplan in PNH subjects;Secondary Objective: Not applicable;Primary end point(s): Safety Endpoints<br>• Incidence and severity of treatment-emergent adverse events<br>• Incidence of thromboembolic events<br>• Laboratory parameters<br>• Electrocardiogram parameters<br><br>Efficacy Endpoints<br>Hemoglobin level<br>• Lactate dehydrogenase level<br>• Indirect bilirubin level<br>• Absolute reticulocyte count<br>• Red blood cell (RBC) transfusions<br>• Functional Assessment of Chronic Illness Therapy–Fatigue scale score;Timepoint(s) of evaluation of this end point: Beginning at Week 12, all subjects will begin to have study visits at 12-week intervals in order to continue the long-term assessment of the safety and efficacy of pegcetacoplan in subjects with PNH
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Pharmacokinetic Endpoint<br>• Pegcetacoplan pharmacokinetic concentrations<br><br>Pharmacodynamic Endpoints<br>• Complement (eg, classical pathway hemolytic activity [CH50], alternative pathway hemolytic activity [AH50], and C3) levels<br>• C3 deposition on RBC cells<br>• Clonal distribution of PNH RBCs<br>• Incidence of anti–pegcetacoplan peptide and anti-PEG antibodies;Timepoint(s) of evaluation of this end point: The PK concentrations will be evaluated using the PK population.<br>Concentrations will be summarized by visit.<br><br>The PD endpoints will be evaluated using the PD population.<br>Absolute values and percentage of baseline will be summarized by visit for AH50 and CH50. For<br>C3, absolute values will be summarized by visit.<br><br>