Clinical Trials Register

Summary
EudraCT Number:	2020-001350-21
Sponsor's Protocol Code Number:	APL2-PNH-209
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-07-11
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Netherlands - Competent Authority

A.2

EudraCT number

2020-001350-21

A.3

Full title of the trial

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

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

A.4.1

Sponsor's protocol code number

APL2-PNH-209

A.5.4

Other Identifiers

Name:

IND

Number:

123,087

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/210/2021

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Apellis Pharmaceuticals, Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Apellis Pharmaceuticals, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Precision for Medicine (HU) Kft.
B.5.2	Functional name of contact point	Clinical Trials Information
B.5.3	Address:
B.5.3.1	Street Address	Alkotás u. 53. E. épület 2. em
B.5.3.2	Town/ city	Budapest
B.5.3.3	Post code	1123
B.5.3.4	Country	Hungary
B.5.6	E-mail	clinicaltrials@precisionformedicine.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Aspaveli
D.2.1.1.2	Name of the Marketing Authorisation holder	Swedish Orphan Biovitrum AB (publ)
D.2.1.2	Country which granted the Marketing Authorisation	Sweden
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/17/1873
D.3 Description of the IMP
D.3.1	Product name	pegcetacoplan
D.3.2	Product code	pegcetacoplan
D.3.4	Pharmaceutical form	Solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Pegcetacoplan
D.3.9.1	CAS number	2019171-69-6
D.3.9.2	Current sponsor code	pegcetacoplan
D.3.9.3	Other descriptive name	pegcetacoplan
D.3.9.4	EV Substance Code	SUB195466
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	54
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Paroxysmal Nocturnal Hemoglobinuria

E.1.1.1

Medical condition in easily understood language

PNH is a rare disorder causing red blood cells to break down too early

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10055629
E.1.2	Term	Paroxysmal nocturnal hemoglobinuria
E.1.2	System Organ Class	100000004857

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

• 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

E.2.2

Secondary objectives of the trial

• 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
• To evaluate the efficacy of pegcetacoplan as assessed by effects on transfusion requirements and episodes of breakthrough hemolysis
• To assess the effect of pegcetacoplan on health-related quality of life (HRQOL) as measured by FACIT-Fatigue and PedsQL General Well-Being Scale
• To assess the long-term safety and efficacy of pegcetacoplan
• To assess the safety of pegcetacoplan as measured by the occurrence of thromboembolic events

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

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.

E.4

Principal exclusion criteria

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.

E.5 End points

E.5.1

Primary end point(s)

Pharmacokinetics
• Pegcetacoplan concentrations and PK parameters over the course of the 16-week treatment period
• Change from baseline to Week 16 in Hb level
• Change from baseline to Week 16 in LDH level
• Change from baseline to Week 16 in ARC
Safety
• Incidence and severity of TEAEs over the course of the 16-week treatment period, including bacterial infections

E.5.1.1

Timepoint(s) of evaluation of this end point

Provided in E.5.1

E.5.2

Secondary end point(s)

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
• Number of transfusions, number of packed RBC units, and total units (mL/kg) transfused over 16 and 52 weeks of treatment with pegcetacoplan
• Occurrence of breakthrough hemolysis over 16 and 52 weeks of treatment with pegcetacoplan
• Change from baseline to Week 52, and from Week 16 to Week 52, in hemoglobin, LDH, and ARC
• 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)
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

E.5.2.1

Timepoint(s) of evaluation of this end point

Provided in E.5.2

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Malaysia

Thailand

United States

Serbia

Czechia

France

Germany

Hungary

Ireland

Italy

Netherlands

Poland

Romania

Spain

United Kingdom

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2022-07-11.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None. Expected normal treatment of the condition.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2022-07-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-10-26

P. End of Trial
P.	End of Trial Status	Ongoing

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