E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
Genetic disease characterized by the occurrence of transitory and recurrent subcutaneous and/or submucosal edemas resulting in swelling and/or abdominal pain |
|
E.1.1.2 | Therapeutic area | Body processes [G] - Genetic Phenomena [G05] |
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 |
|
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 safety of extended dosing (52 weeks), and alternative dosing and/or dose frequency with ISIS 721744 in patients with HAE |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of extended dosing (52 weeks), and alternative dosing and/or dose frequency with ISIS 721744 in patients with HAE |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Satisfactory completion of ISIS 721744-CS2 (index study) through
Week 17 with an acceptable safety and tolerability profile, per Sponsor and Investigator judgement
2. Able and willing to participate in a 64-week study
3. Females must be non-pregnant, non-lactating and either surgically sterile or post-menopausal
4. Males must be surgically sterile or abstinent* or if engaged in sexual relations with a female of child-bearing potential, participant is utilizing an acceptable contraceptive method Participants must have access to, and the ability to use, ≥ 1 acute medication(s) (e.g., plasma-derived or recombinant C1- inhibitor (C1-INH) concentrate or a bradykinin-2 [BK-2] antagonist) to treat angioedema attacks |
|
E.4 | Principal exclusion criteria |
1. Have any new condition or worsening of an existing condition or change or anticipated change in medication or other reason, which in the opinion
of the Investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating in or completing the study |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of Participants with at Least One Treatment-emergent Adverse Event (TEAE), Graded by Severity |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
adverse events will be collected at each visit |
|
E.5.2 | Secondary end point(s) |
-The time-normalized HAE attacks (monthly) by treatment
-Plasma PKK levels, plasma proenzyme activation and cHK levels
-Consumption of on-demand medications
-AE-QoL questionnaire score |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
-During the study patients will be instructed to report details of any HAE attack to the study site within 72 hours of the onset of the attack
-Plasma PKK levels, plasma proenzyme activation and cHK levels will be measured at Weeks 1, 5, 9, 13, 21, 29, 37, 45, 53, 65.
For patients switching to option 2 or 3, there will be additional timepoints
-During the study patients will be instructed to report details of any on-demand treatment to the study site within 72 hours of the onset of the attack
-AE-QOL questionnaire will be completed at Weeks 1, 13, 25, 37, 53 and 65 |
|
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 | Yes |
E.6.13.1 | Other scope of the trial description |
|
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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 |
Netherlands |
United Kingdom |
United States |
|
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
|
The End-of-Study is defined as the date of the last visit of the last patient in the study |
|
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 | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |