|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Paroxysmal Nocturnal Hemoglobinuria (PNH)
|Medical condition in easily understood language
|Paroxysmal Nocturnal Hemoglobinuria
|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
|To confirm the safety and tolerability of zilucoplan in subjects with PNH
To confirm the efficacy of zilucoplan in subjects with PNH
|Secondary objectives of the trial
|Trial contains a sub-study
|Principal inclusion criteria
|To be eligible for this study, subjects must meet ALL the following inclusion criteria:
1. Male or female ≥18 years and <85 years
2. Able to provide informed consent, including signing and dating the informed consent form (ICF).
3. Diagnosis of PNH by flow cytometry.
4. Subjects must not have received treatment with eculizumab or another complement inhibitor within 6 months prior to Screening.
5. Subjects must have a lactate dehydrogenase (LDH) level ≥2 times the upper limit of normal (xULN) during Screening.
6. Subjects must be transfusion-dependent, defined as receiving at least one qualifying transfusion (for Hb ≤9g/dL with symptoms of anemia; or for Hb ≤7g/dL irrespective of symptoms) in the 6 months prior to Screening.
7. Female subject of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test within 24 hours prior to the first dose of study drug.
8. Sexually active female subjects of childbearing potential (i.e., women who are not postmenopausal or who have not had a hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) and all male subjects (who have not been surgically sterilized by vasectomy) must agree to use effective contraception during the study.
|Principal exclusion criteria
|Subjects who meet ANY of the following exclusion criteria will be excluded from the study:
1. Platelet count <50,000/μL or absolute neutrophil count (ANC) <500 cells/μL at Screening.
2. Calculated glomerular filtration rate of <30 mL/min/1.73m2 based on the Modification of Diet in Renal Disease (MDRD) equation at Screening.
3. Elevation of liver function tests: alanine aminotransferase (ALT) >2xULN or Direct Bilirubin and Alkaline Phosphatase both >2xULN.
4. Elevation of amylase or lipase >2xULN.
5. History of meningococcal disease.
6. Current or recent systemic infection within 2 weeks prior to Screening or infection requiring intravenous (IV) antibiotics within 4 weeks prior to Screening.
7. Pregnant, planning to become pregnant, or nursing female subjects.
8. History of bone marrow transplantation, or expected to undergo bone marrow transplantation during the 6-month treatment period.
9. Recent surgery requiring general anesthesia within 2 weeks prior to Screening or expected to have surgery requiring general anesthesia during the 6-month Treatment Period.
10. Active malignancy (except curatively resected squamous or basal cell carcinoma of the skin) requiring surgery, chemotherapy, or radiation within the prior 12 months (subjects with a history of malignancy who have undergone curative resections or otherwise not requiring a treatment for at least 12 months prior to Screening with no detectable recurrence are allowed).
11. History of any significant medical or psychiatric disorder that in the opinion of the investigator would make the subject unsuitable for participation in the study.
12. Treatment with any investigational medicinal product or investigational device within 30 days prior to Screening.
13. Participation in another concurrent clinical trial involving an investigational, therapeutic intervention (participation in observational studies and or registry studies is permitted).
14. Unable or unwilling to comply with the requirements of the study.
|E.5 End points
|Primary end point(s)
|1.Hemoglobin stabilization defined as: maintenance of hemoglobin concentration greater than the individual set point for each subject (based on the qualifying transfusion) and avoidance of any RBC transfusion over 6 months.
2. Change in serum LDH from baseline to Week 24 (Day 168).
|Timepoint(s) of evaluation of this end point
|Secondary end point(s)
|1. Transfusion independence: defined as subject not receiving any RBC transfusions over the 6-month study period.
2. Changes from baseline in quality of life (QOL) questionnaires (e.g., FACIT-Fatigue, EQ-5D, and WPAI:SHP).
|Timepoint(s) of evaluation of this end point
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Other scope of the trial description
|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)
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the 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