E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with Paroxysmal Nocturnal Hemoglobinuria Who Have Clinically Evident Extravascular Hemolysis (EVH) |
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E.1.1.1 | Medical condition in easily understood language |
Patients with Paroxysmal Nocturnal Hemoglobinuria Who Have Clinically Evident Extravascular Hemolysis (EVH) |
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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 | 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 | 10038359 - Renal and urinary disorders |
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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 of danicopan as compared to placebo as add-on therapy to a C5 inhibitor at 12 weeks |
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E.2.2 | Secondary objectives of the trial |
• Percentage Of Participants with Hgb increase of ≥2 g/dL in the absence of transfusion •Percentage Of Participants With Transfusion Avoidance • Change From Baseline In Functional Assessment Of Chronic Illness Therapy (FACIT) Fatigue Scores • Change From Baseline In Absolute Reticulocyte Count |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Diagnosis of PNH • Clinically evident extravascular hemolysis (EVH) defined by: - Anemia (Hgb ≤9.5 gram/deciliter) with absolute reticulocyte count ≥ 120 x 10^9/liter. • Receiving a C5 inhibitor for at least 6 months prior to Day. • Platelet count ≥30,000/microliters (μL) • Absolute neutrophil counts ≥500/μL. • Documentation of/or willingness to receive vaccinations and prophylactic antibiotics as required. |
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E.4 | Principal exclusion criteria |
• History of a major organ transplant or hematopoietic stem cell transplantation (HSCT). • Participants with known aplastic anemia or other bone marrow failure that requires HSCT or other therapies including anti-thymocyte globulin and/or immunosuppressants, unless the dosage regimen of immunosuppressant has been stable for at least 12 weeks before Day 1 and patient is expected to remain on stable doses through Week 24. • Known or suspected complement deficiency. • Laboratory abnormalities at screening, including: - Alanine aminotransferase >2 x ULN (> 3 x ULN in the case of patients with documented liver iron overload defined by serum ferritin values ≥ 500 ng/mL). The inclusion of patients with documented iron overload and ALT>2 X ULN will be done in a case by case basis, with prior discussion with the Medical Monitor. - Direct bilirubin >2 x ULN - patients who, in the opinion of investigator, have direct bilirubin > 2 x ULN due to EVH and/or patients with documented Gilbert's Syndrome. If Gilbert's syndrome is suspected, the patient will be tested for this condition at screening. • Current evidence of biliary cholestasis • Estimated glomerular filtration rate <30 milliliters/minute/1.73 meter squared and/or are on dialysis. • Evidence of human immunodeficiency virus, hepatitis B, or active hepatitis C infection at screening |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Change From Baseline In Hemoglobin (Hgb) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Percentage of patients with Hgb increase of ≥ 2 g/dL in the absence of transfusion • Percentage Of Participants With Transfusion Avoidance • Change From Baseline In Functional Assessment Of Chronic Illness Therapy (FACIT) Fatigue Scores; Scoring 0-52 • Change From Baseline In Absolute Reticulocyte Count |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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 | No |
E.6.10 | Pharmacogenetic | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 29 |
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 |
Argentina |
Malaysia |
Taiwan |
Brazil |
Canada |
Israel |
Japan |
Korea, Republic of |
Thailand |
United Kingdom |
United States |
Czechia |
France |
Germany |
Greece |
Italy |
Netherlands |
Poland |
Spain |
Türkiye |
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |