|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Paroxysmal Nocturnal Hemoglobinuria
|Medical condition in easily understood language
|PNH is a rare disorder causing red blood cells to break down too early
|Diseases [C] - Blood and lymphatic diseases [C15]
|E.1.2 Medical condition or disease under investigation
|Paroxysmal nocturnal hemoglobinuria
|System Organ Class
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|The objectives of this study are to:
1. Establish the long-term safety of Pegcetacoplan (APL-2) in PNH subjects
2. Establish the long-term efficacy of Pegcetacoplan (APL-2) in PNH subjects
|Secondary objectives of the trial
|Trial contains a sub-study
|Principal inclusion criteria
|1. Subjects at least 18 years of age with PNH who have participated in a Pegcetacoplan (APL-2) clinical trial.
Subjects who received treatment with Pegcetacoplan (APL-2) must have experienced
clinical benefit and adequate tolerability in the opinion of the Investigator.
Note: Subjects with PNH who completed an Pegcetacoplan (APL-2) clinical trial without
receiving Pegcetacoplan (APL-2) (or without receiving Pegcetacoplan (APL-2) 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 (APL-2) 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
5. Women of childbearing potential (WOCBP), 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.
|Principal exclusion criteria
|1. Subjects who withdrew from a Pegcetacoplan (APL-2) clinical study 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. Known infection with hepatitis B, C, or HIV.
6. Hereditary complement deficiency.
7. History of bone marrow transplant.
8. Concurrent severe aplastic anemia (SAA), defined as currently receiving
immunosuppressive therapy for SAA including but not limited to cyclosporin A,
tacrolimus, mycophenolate mofetil, or anti-thymocyte globulin.
9. History of meningococcal disease.
10. Concomitant treatment with any complement inhibitor (eg, eculizumab, ravulizumab).
11. Pregnancy, breastfeeding, or positive pregnancy test.
|E.5 End points
|Primary end point(s)
• Incidence and severity of Treatment-emergent Adverse Events (TEAE)
• Incidence of thromboembolic events
• Laboratory parameters
• ECG parameters
• Lactate dehydrogenase (LDH) level
• Absolute Reticulocyte count (ARC)
• Hemoglobin level
• Red blood cell (RBC) transfusions
• FACIT-fatigue scale score
|Timepoint(s) of evaluation of this end point
• Incidence and severity of Treatment-emergent Adverse Events (TEAE): after dosing begins, or worsen of severity, for up to 30 days after the last dose of Pegcetacoplan (APL-2)
• Incidence of thromboembolic events:
after dosing begins for up to 30 days after the last dose of Pegcetacoplan (APL-2)
• Laboratory parameters: Please refer to Schedule Events in Protocol
• ECG parameters: Please refer to Schedule Events in Protocol
Please Refer to Schedule Events in Protocol
|Secondary end point(s)
• Pegcetacoplan (APL-2) pharmacokinetic concentrations
• Complement (e.g., CH50, AH50, and C3) levels
• C3 deposition on RBC cells
• Clonal distribution of PNH RBCs
• Incidence of anti-APL-2 and anti-PEG antibodies
|Timepoint(s) of evaluation of this end point
Blood samples will be collected at the time points delineated in the Schedule of Events in Section 3 of Protocol
Pharmacodynamic Endpoints: Blood samples will be collected at the time points delineated in the Schedule of Events in Section 3 of Protocol
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
|Korea, Republic of
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months
|In all countries concerned by the trial days