E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with acute attacks of hereditary angioedema.
|
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019860 |
E.1.2 | Term | Hereditary angioedema |
|
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 demonstrate the efficacy of rhC1INH in the treatment of acute attacks in patients with HAE. |
|
E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability of rhC11NH in symptomatic patients with HAE. To assess the safety, tolerability, efficacy as well as PK and PD of rhC11NH in the open-label treatment of subsequent attacks of HAE.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Screening •Aged at least 16 years •Signed written informed consent •Clear clinical and laboratory diagnosis of HAE with baseline plasma level of functional C1INH of less than 50 % of normal. Open-label treatment •Above criteria •Evidence for exacerbation or development of an abdominal attack and/or of facial-oro-pharyngeal angioedema and/or laryngeal angioedema and/or of genito-urinary angioedema and/or peripheral angioedema. Patients must notify and discuss symptoms with the investigator prior to travelling to the study centre. •Onset of eligible symptoms not longer than 5 h ago. •Patient’s VAS score of overall severity of angioedema symptoms at least at one location at the time of evaluation ( t = - 1 h) of at least 50 mm, where 0 mm means ‘no symptoms at all’ and 100 mm means ‘extremely disabling’. This inclusion criterion is set to allow suffcient room for improvement in response to study medication. •No clear regression of angioedema signs by VAS at t = 0 h; just prior to the administration of study medication. Thus, no beginning of relief by VAS at t = 0 h (reduction of 20 mm or more) compared with VAS score at determination of eligibility, t = - 1 h. •Above screening and treatment criteria continue to be met for subsequent eligible attack • Day 22 post-randomized treatment follow-up visit has occurred. •Minimum interval of 22 Days between subsequent open-label treatments
|
|
E.4 | Principal exclusion criteria |
Screening •A history of administration of pharmaceuticals derived from rabbits (e g. antisera, rhC1INH) in conjunction with any evidence of a relation with allergic reactions. •A history of anaphylaxis, or severe allergies (i.e. requiring medication) to food, proteins and/or drugs. •A history of allergic reactions to C1INH concentrates or rabbit protein. •A diagnosis of acquired C1INH deficiency (exclude patients with AAE). •Pregnancy, breast-feeding or current intention to become pregnant. •Known or suspected addiction to narcotics. •Blood donation in the past 3 months. •Participation in another clinical study in the past 3 months or participation in two or more clinical studies prior to this study in the last 12 months. •Any clinically significant abnormality in the routine hematology, biochemistry and urinalysis. •Any condition or treatment that in the opinion of the investigator might interfere with the evaluation of the study objectives. Open-label treatment •Above criteria; no (expected) clinically significant abnormalities in routine laboratory analyses. •Patients presenting or developing a life-threatening attack (an attack requiring immediate emergency procedures to prevent death, hypoxemia related injuries or other unfavorable outcomes). • Any reported SAE related to (randomized or open-label) study drug administration. • Any changes since screening and/or the moment of diagnosis of the present eligible attack that would exclude subject based on above exclusion criteria. • Patients presenting or developing a life-threatening attack (an attack requiring immediate emergency procedures to prevent death, hypoxemia related injuries or other unfavorable outcomes).
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
•Time to the beginning of relief based on patient’s VAS scores. This variable will be based on the overall VAS for each eligible location (abdominal and/or facial-oro-pharyngeal-laryngeal and/or genito-urinary and/or peripheral). Time to the beginning of relief is defined as the first assessment time at which the overall VAS decreases by at least 20 mm with respect to baseline. For single attacks involving more than one (eligible) location, time to the beginning of relief is based on a decrease of at least 20 mm for any location. For single attacks involving more than one (eligible; at least 50 mm at baseline) location, the location with the earliest response will be used for statistical analysis.
|
|
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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
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 | No |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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
|
Thirty eligible patients will have been treated for 3 eligible attacks and followed up until 90 Days after treatment. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
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 | 0 |