E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
non-histaminergic angioedema with normal C1-INH |
nem-hisztaminerg angioödéma normál C1-INH-val |
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E.1.1.1 | Medical condition in easily understood language |
Angioedema is a long-term and life-threatening disease. It manifests clinically as unpredictable, intermittent attacks of edema of the face, larynx, gastrointestinal tract, limbs and/or genitalia. |
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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 | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10002425 |
E.1.2 | Term | Angioedemas |
E.1.2 | System Organ Class | 100000004858 |
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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 |
Primary: To evaluate the long-term safety of repeated subcutaneous (SC) administrations of lanadelumab in adolescents and adults with non-histaminergic angioedema with normal C1-INH
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E.2.2 | Secondary objectives of the trial |
Secondary:
- To evaluate the long-term efficacy of lanadelumab in preventing angioedema attacks
- To characterize pharmacokinetics (PK) and pharmacodynamics (PD) following long-term SC administration of lanadelumab
- To assess the immunogenicity of chronically administered lanadelumab
- To evaluate the effect of lanadelumab on health-related quality of life (HR-QoL)
- To evaluate subject experience of injection
- To evaluate the safety and efficacy of lanadelumab in subjects switched to the dosing regimen of 300 mg every 4 weeks (q4wks) lanadelumab |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Males and females, 12 years of age and older diagnosed with non-histaminergic normal C1-INH angioedema at the time of enrollment into the antecedent Study SHP643-303.
2. Subjects must have completed the treatment period (through Day 182) of Study SHP643-303 without reporting a clinically significant treatment-emergent adverse event (TEAE) that would preclude subsequent exposure to lanadelumab.
3. Agree to adhere to the protocol-defined schedule of treatments, assessments, and procedures.
4. Males, or non-pregnant, non-lactating females who are of child-bearing potential and who agree to be abstinent or agree to comply with the applicable contraceptive requirements of this protocol for the duration of the study;
or females of non-childbearing potential, defined as surgically sterile (status post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or post-menopausal for at least 12 months.
5. The subject (or the subject’s parent/legal guardian, if applicable) has provided written informed consent approved by the institutional review board/research ethics board/ethics committee (IRB/REB/EC) at any time prior to study start. If the subject is a minor (ie, <18 years of age), have a parent/legal guardian who is informed of the nature of the study provide written informed consent (ie, permission) for the minor to participate in the study before any study-specific procedures are performed. Assent will be obtained from minor subjects. |
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E.4 | Principal exclusion criteria |
1. Discontinued from Study SHP643-303 after enrollment but before Visit 26 for any reason.
2. Presence of important safety concerns identified in Study SHP643-303 that would preclude participation in this study.
3. Dosing with an investigational product (IP, not including IP defined in antecedent Study SHP643-303) or exposure to an investigational device within 4 weeks prior to Day 0.
4. Subject has a known hypersensitivity to the investigational product or its components.
5. Have any condition (surgical or medical) that, in the opinion of the investigator or sponsor, may compromise their safety or compliance, preclude the successful conduct of the study, or interfere with interpretation of the results (eg, significant pre-existing illness or other major comorbidities that the investigator considers may confound the interpretation of study results). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety measures, including:
- Adverse events (AEs), including serious adverse events (SAEs) and adverse events of special interest (AESI)
- Clinical laboratory testing (hematology, clinical chemistry, coagulation, and urinalysis)
- Vitals signs including blood pressure, heart rate (HR), body temperature
- Weight and height (height for subjects <18 years old)
- 12-lead ECGs |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
multiple timepoints as per Protocol's Schedule of Activities |
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E.5.2 | Secondary end point(s) |
- Number of investigator-confirmed angioedema attacks during the treatment period
- Number of moderate or severe angioedema attacks during the treatment period
- Number of high-morbidity angioedema attacks during the treatment period; a high-morbidity angioedema attack is defined as any attack that has at least one of the following characteristics: severe, results in hospitalization (except hospitalization for observation <24 hours), hemodynamically significant (systolic blood pressure <90 mmHg, requires intravenous (IV) hydration, or associated with syncope or near-syncope) or laryngeal.
- Analysis of pharmacokinetics (PK) effects through measurement of plasma concentrations of lanadelumab.
- Evaluation of the pharmacodynamic (PD) effects of lanadelumab through cHMWK and fluorogenic plasma kallikrein (pKal) assay with FXIIa activation.
- Presence of anti-drug antibodies (ADAs), including evaluation of neutralizing antibodies (if any confirmed positive anti-drug antibodies are detected)
- Health-related quality of life assessments will be assessed using the AE-QoL questionnaire.
- Lanadelumab Injection Report
Safety measures, including:
- AEs, including SAEs and AESIs
- Clinical laboratory testing (hematology, clinical chemistry, coagulation, and urinalysis)
- Vitals signs including blood pressure (BP), HR, body temperature
- Weight and height (height for subjects <18 years old)
- 12-lead ECGs
Efficacy measures, including:
- Number of investigator-confirmed angioedema attacks during the treatment period
- Number of moderate or severe angioedema attacks during the treatment period
- Number of high-morbidity angioedema attacks during the treatment period; a high-morbidity angioedema attack is defined as any attack that has at least one of the following characteristics: severe, results in hospitalization (except hospitalization for observation <24 hours), hemodynamically significant (systolic blood pressure <90 mmHg, requires IV hydration, or associated with syncope or near-syncope) or laryngeal. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
multiple timepoints as per Protocol's Schedule of Activities |
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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 | No |
E.6.11 | Pharmacogenomic | Yes |
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.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
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 |
Japan |
United States |
France |
Germany |
Hungary |
Italy |
Netherlands |
Poland |
Spain |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |