E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Paroxysmal Nocturnal Hemoglobinuria |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
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 |
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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 assess the safety and tolerability of long-term monotherapy with BCX9930 in subjects with paroxysmal nocturnal hemoglobinuria (PNH) who previously received BCX9930 in a BioCryst-sponsored study |
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E.2.2 | Secondary objectives of the trial |
• To assess the continued effectiveness of BCX9930 in treatment of PNH during long-term administration • To evaluate the effects of long-term monotherapy with BCX9930 on the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale and Quality of Life Questionnaire for Patients with Aplastic Anemia/PNH (QLQ-AA/PNH) • To characterize plasma concentrations of BCX9930 and its metabolite BCX13559 (M1a) throughout the treatment period • To characterize the effects of long-term BCX9930 monotherapy in subjects with PNH on pharmacodynamic (PD) and complement biomarkers
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Able to provide written informed consent. 2. Non-pregnant, non-lactating female subjects. 3. Subjects with PNH who have completed treatment in another BCX9930 clinical study and, in the opinion of the investigator, would benefit from continued treatment with BCX9930. 4. Female participants will continue to meet at least one of the following requirements per the prior study: a. Be a woman of nonchildbearing potential. b. Be a woman of childbearing potential who agrees to use a highly effective contraceptive method throughout the study and for a duration of 30 days after the last dose of BCX9930. c. Alternatively, true abstinence is acceptable for women of childbearing potential when it is in line with the subject’s preferred and usual lifestyle. 5. Male participants will continue to meet at least one of the following requirements per the prior study: a. Males with a female partner of childbearing potential (including a pregnant partner) must use condoms throughout the study and for a duration of 90 days after the dose of BCX9930 unless their partner is using a highly effective contraceptive method independent of the study. b. Alternatively, true abstinence is acceptable when it is in line with the subject’s preferred and usual lifestyle. 6. In the opinion of the investigator, the subject is expected to adequately comply with all required study procedures and restrictions for the study
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E.4 | Principal exclusion criteria |
1. Any clinically significant medical or psychiatric condition including alcohol or drug dependency that, in the opinion of the investigator or sponsor, would interfere with the subject’s ability to participate in the study or increase the risk of participation for that subject. 2. An ongoing adverse event (AE), including a laboratory abnormality, or other unacceptable toxicity that, in the judgment of the investigator, compromises the ability of the subject to continue study-specific procedures or it is considered not to be in the subject’s best interest to continue or benefit-risk assessment is no longer in favor of the subject’s continued treatment. 3. Daily use of medications listed in the currently applicable prohibited medications list. 4. Known or suspected hypersensitivity to BCX9930 or any of its formulation excipients (Note: prior drug rash is not exclusionary).
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E.5 End points |
E.5.1 | Primary end point(s) |
• Subject incidence of graded treatment-emergent adverse events (TEAEs), laboratory abnormalities, changes to vital signs, electrocardiogram (ECG) results, and physical examination findings |
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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) |
• Change from baseline (CFB) in hemoglobin (Hb) • Proportion of subjects with Hb ≥ 12 g/dL • Proportion of subjects with Hb stabilization, defined as avoidance of a > 2 g/dL decrease in the absence of transfusion • Percent CFB in lactate dehydrogenase (LDH) • Number of units of packed red blood cells (pRBCs) transfused • Proportion of subjects who are transfusion-free • CFB in FACIT-Fatigue scale score through 48 weeks of treatment in Study 205 • CFB in QLQ-AA/PNH scores through 48 weeks of treatment in Study 205 • Plasma concentrations of BCX9930 and BCX13559 at steady state in subjects with PNH
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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 | 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 | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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 | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
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 | 25 |
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 |
Brazil |
Canada |
China |
Colombia |
Hong Kong |
Japan |
Korea, Republic of |
Malaysia |
Philippines |
South Africa |
Taiwan |
United States |
Austria |
France |
Lithuania |
Netherlands |
Romania |
Spain |
Czechia |
Italy |
Azerbaijan |
Hungary |
Slovakia |
Turkey |
United Kingdom |
Serbia |
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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 |