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
- Conditions
- PNH10018911
- Registration Number
- NL-OMON54475
- Lead Sponsor
- Apellis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 1
1. Between the ages of 12 and 17, inclusive, at time of study entry. 2. A
diagnosis of PNH, confirmed by high-sensitivity flow cytometry (granulocyte or
monocyte clone >10%). 3. Be either a nai*ve patient or a switch patient, as
defined below. a. A nai*ve 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. 4. Platelet count
>75,000/mm3. 5. Absolute neutrophil count >1000/mm3. 6. Weigh at least 20 kg.
7. Have a body mass index (BMI) that is less than the 95th percentile for their
age. 8. 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 9.
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. 10. 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. 11. 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. 12. Willing and able to
self-administer pegcetacoplan or has a caregiver who is willing and able to do
so. 13. 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 rest
1. Known or suspected hereditary fructose intolerance (HFI).
2. Active bacterial infection that has not resolved within at least 1 week
before the first dose of pegcetacoplan.
3. Hereditary complement deficiency.
4. History of bone marrow transplantation.
5. History or presence of hypersensitivity or idiosyncratic reaction to
compounds related to the formulation or SC administration of pegcetacoplan.
6. 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.
7. Planning to become pregnant during study participation, or currently
breastfeeding.
8. History of meningococcal disease.
9. 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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary objectives of this study are:<br /><br>• To define the pharmacokinetics of pegcetacoplan in adolescents with PNH<br /><br>• To evaluate the efficacy of pegcetacoplan based on Hb level, LDH level, and<br /><br>ARC<br /><br>• To assess the safety of pegcetacoplan as measured by the incidence and<br /><br>severity of treatment-emergent adverse events (TEAEs), including bacterial<br /><br>infections</p><br>
- Secondary Outcome Measures
Name Time Method <p>The secondary objectives of this study are:<br /><br>• To assess the pharmacodynamics and biological activity of pegcetacoplan as<br /><br>measured by effects on complement levels, C3 deposition on RBCs, and clonal<br /><br>distribution of PNH RBCs<br /><br>• To evaluate the efficacy of pegcetacoplan as assessed by effects on<br /><br>transfusion requirements and episodes of breakthrough hemolysis<br /><br>• To assess the effect of pegcetacoplan on health-related quality of life<br /><br>(HRQOL) as measured by FACIT-Fatigue and PedsQL General Well-Being Scale<br /><br>• To assess the long-term safety and efficacy of pegcetacoplan<br /><br>• To assess the safety of pegcetacoplan as measured by the occurrence of<br /><br>thromboembolic events</p><br>