E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10019860 |
E.1.2 | Term | Hereditary angioedema |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic 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 monitor the long-term safety of berotralstat |
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E.2.2 | Secondary objectives of the trial |
To provide continued access to berotralstat to subjects who have participated in Studies BCX7353-302 (Study 302) and BCX7353-204 (Study 204), are expected to continue benefiting from treatment with berotralstat, and do not have other means of access to berotralstat |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Males and non-pregnant, non-lactating females who are currently enrolled as a subject or were previously enrolled and did not discontinue due to an adverse event or due to noncompliance in BioCryst-sponsored Study 302 or 204 2. Able to provide written informed consent. Subjects who are aged 12 to 17 years of age must be able to read, understand, and be willing to sign an assent form in addition to an applicable representative providing informed consent. 3. Would benefit from continued berotralstat treatment in the opinion of the investigator 4. Female subjects must meet at least 1 of the following requirements: a. Be a WOCBP (defined as a female following menarche and prior to becoming post-menopausal who has not had a hysterectomy or bilateral salpingectomy and bilateral oophorectomy) who agrees to use at least an acceptable effective contraceptive method during the study. b. Be a woman of nonchildbearing potential (defined as postmenopausal [no menses for at least 12 months without an alternative medical cause] or has had a hysterectomy or a bilateral salpingectomy and bilateral oophorectomy). 5. In the opinion of the investigator, the subject is expected to adequately comply with all required study procedures. |
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E.4 | Principal exclusion criteria |
1. Any condition or situation, including medical history or changes in medical history, which, in the opinion of the investigator or sponsor, would interfere with the subject’s safety or ability to participate in the study 2. Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent. 3. Hypersensitivity to the active substance or to any of the excipients in the IMP. 4. Use of other medications for long-term prophylaxis of HAE attacks at the Baseline visit or any time during the study. These include: C1-INH, tranexamic acid, androgens, or lanadelumab. 5. Use of any other investigational medicinal product at the Baseline visit or any time during the study. 6. Pregnancy or breastfeeding. 7. Subjects with an immediate family relationship to either sponsor employees, the investigator, or employees of the study site who are named on the delegation log. 8. Subjects who are held in an institution by a governmental or judicial order. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Number and proportion of subjects with a treatment-related TEAE Number and proportion of subjects who experience a serious adverse event (SAE) Number and proportion of subjects who experience a treatment-related Grade 3 or 4 TEAE Number and proportion of subjects who experience a treatment-related Grade 3 or 4 treatment-emergent chemistry abnormality Number and proportion of subjects who discontinue due to a TEAE |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Week 240 or until another mechanism is available to provide berotralstat (eg, market access). |
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E.5.2 | Secondary end point(s) |
Another mechanism is available to provide drug to the subject(eg, market access), or until the sponsor discontinues all global commercialization and development of berotralstat for the prevention of angioedema attacks, whichever comes first |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 240 or until another mechanism is available to provide berotralstat (eg, market access). |
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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 | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
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) | 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 | 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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
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 |
North Macedonia |
Korea, Republic of |
South Africa |
European Union |
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E.8.7 | Trial has a data monitoring committee | No |
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 | 5 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |