A single arm study to evaluate the safety and biological activity of pegcetacoplan in patients 12- 17 years old with paroxysmal nocturnal hemoglobinuria

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Apellis Pharmaceuticals Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

22 Oct 2021 → ongoing

Decision date (initial)

2024-09-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Apellis Pharmaceuticals, Inc.

External identifiers

EU CT number

2024-516350-22-00

EudraCT number

2020-001350-21

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Pharmacokinetic, Efficacy, Safety

• To define the pharmacokinetics of pegcetacoplan in adolescents with PNH
• To evaluate the efficacy of pegcetacoplan based on Hb level, LDH level, and ARC
• To assess the safety of pegcetacoplan as measured by the incidence and severity of treatment-emergent adverse events (TEAEs), including bacterial infections

Secondary objectives 5

1. To assess the pharmacodynamics and biological activity of pegcetacoplan as measured by effects on complement levels, C3 deposition on RBCs, and clonal distribution of PNH RBCs
2. To evaluate the efficacy of pegcetacoplan as assessed by effects on transfusion requirements and episodes of breakthrough hemolysis
3. To assess the effect of pegcetacoplan on health-related quality of life (HRQOL) as measured by FACIT-Fatigue and PedsQL General Well-Being Scale
4. To assess the long-term safety and efficacy of pegcetacoplan
5. To assess the safety of pegcetacoplan as measured by the occurrence of thromboembolic events

Conditions and MedDRA coding

Paroxysmal Nocturnal Hemoglobinuria

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002600-PIP01-19

Plan to share IPD

Yes

IPD plan description

Requests for access to the deidentified data will be reviewed by Apellis External Research Committee.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

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 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
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 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 9

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. Pharmacokinetics: Pegcetacoplan concentrations and PK parameters over the course of the 16-week treatment period
2. Efficacy and Pharmacodynamics: Change from baseline to Week 16 in Hb level
3. Efficacy and Pharmacodynamics: Change from baseline to Week 16 in LDH level
4. Efficacy and Pharmacodynamics: Change from baseline to Week 16 in ARC
5. Safety: Incidence and severity of TEAEs over the course of the 16-week treatment period, including bacterial infections

Secondary endpoints 6

1. 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
2. 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
3. Efficacy and Pharmacodynamics: Occurrence of breakthrough hemolysis over 16 and 52 weeks of treatment with pegcetacoplan
4. Efficacy and Pharmacodynamics: Change from baseline to Week 52, and from Week 16 to Week 52, in hemoglobin, LDH, and ARC
5. 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)
6. 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Apellis Pharmaceuticals Inc.

Sponsor organisation

Apellis Pharmaceuticals Inc.

Address

100 5th Avenue

City

Waltham

Postcode

02451-8703

Country

United States

Scientific contact point

Organisation

Apellis Pharmaceuticals Inc.

Contact name

Clinical Trial

Public contact point

Organisation

Apellis Pharmaceuticals Inc.

Contact name

Clinical Trial

Third parties 14

Locations

2 EU/EEA countries · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications