E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Paroxysmal Nocturnal Hemoglobinuria (PNH) |
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E.1.1.1 | Medical condition in easily understood language |
Paroxysmal Nocturnal Hemoglobinuria (PNH) |
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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 | 18.0 |
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 |
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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 evaluate the efficacy, safety, and tolerability of multiple doses of ALXN1210 administered intravenously (IV) to complement inhibitor treatment-naïve patients with PNH |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the trial are:
- To characterize the pharmacokinetic (PK) and pharmacodynamic (PD) effects of multiple doses of ALXN1210 administered IV to complement inhibitor treatment-naïve patients with PNH
- To investigate the immunogenicity of ALXN1210 administered IV to complement inhibitor treatment-naïve patients with PNH |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female patients ≥ 18 years of age
2. PNH diagnosis confirmed by documented high-sensitivity flow cytometry (red blood cells [RBCs] and/or granulocytes)
3. Mean lactate dehydrogenase (LDH) ≥3 × upper limit of normal, based on 2 measurements from separate blood samples collected at least 1 day apart during screening
4. Willing and able to give written informed consent and comply with the study visit schedule
5. Documented meningococcal vaccination not more than 3 years prior to dosing
6. Female patients who consider themselves postmenopausal must provide evidence at screening of menopause status, based on a combination of amenorrhea for at least 1 year and increased serum follicle-stimulating hormone level (> 30 IU/L) on at least 2 occasions (eg, in the absence of hormone replacement therapy, dietary phytoestrogens) or estradiol concentration < 10 pg/mL.
7. Female patients of childbearing potential must use highly effective contraception as defined below, starting at screening and continuing until at least 6 months after the last dose of ALXN1210.
8. Male patients with a female spouse/partner of childbearing potential or a pregnant or breastfeeding spouse or partner must agree to use barrier contraception (male condom) during the Treatment Period and for at least 6 months after the last dose of ALXN1210. Barrier contraception is required even with documented medical assessment of surgical success of a vasectomy. Female spouses/partners of male patients who are of childbearing potential must use highly effective contraception or acceptable contraception, as defined below, starting at screening and continuing until at least 6 months after the last dose of ALXN1210. Male patients must not donate sperm during the
Screening and Treatment Periods and for at least 6 months after the last dose of ALXN1210.
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E.4 | Principal exclusion criteria |
1. Treatment with a complement inhibitor at any time
2. Platelet count < 30,000/mm3 (30 × 109 /L) at screening
3. Absolute neutrophil count < 500/μL (0.5 × 109 /L) at screening
4. History of bone marrow transplantation
5. History of Neisseria meningitidis infection; history of unexplained, recurrent infection; or infection requiring treatment with systemic antibiotics within the last 90 days prior to dosing on Day 1
6. Female patients who are planning to become pregnant, or are pregnant or breastfeeding |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in LDH levels from baseline to Day 253 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Day 1, 7, 15, 22, 29, 43, 57, 85, 113, 127, 141, 169, 197, 211, 225, 253
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E.5.2 | Secondary end point(s) |
Efficacy endpoints:
- Changes in hemolysis-related hematologic parameters
- Changes in clinical manifestations
Safety endpoints:
- Change from baseline in the need for blood transfusions
- Change from baseline in disease-associated biomarkers
- Change from baseline in quality of life
- Change from baseline in major adverse vascular events (MAVEs)
Immunogenicity: Measurement of antidrug antibodies (ADA)
Pharmacokinetic/Pharmacodynamic
Safety |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Day 1, 7, 15, 22, 29, 43, 57, 85, 113, 127, 141, 169, 197, 211, 225, 253
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
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 | No |
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 |
Canada |
Finland |
France |
Germany |
Russian Federation |
Spain |
Sweden |
Taiwan |
United Kingdom |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |