E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Abdominal aortic aneurysm (AAA) is a dilatation of the aorta as it passes through the
abdomen, defined as a dilatation of the infra-renal aorta to a diameter of 30 mm. AAA is
generally asymptomatic and the greatest concern is the risk of rupture, which causes severe
pain, massive internal hemorrhage, and, without prompt treatment, death. |
|
E.1.1.1 | Medical condition in easily understood language |
Abdominal aortic aneurysm (AAA) is generally asymptomatic and the greatest concern is the risk of rupture, which causes severe pain, massive internal hemorrhage, and, without prompt treatment, death. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000054 |
E.1.2 | Term | Abdominal aortic aneurysm |
E.1.2 | System Organ Class | 10047065 - Vascular disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the optimal oral dose of CRD007 (10 mg, 25 mg and 40 mg tablets) in
comparison to matching placebo tablets with respect to efficacy in terms of change in
maximum aortic diameter after 12 months of treatment (b.i.d.) as assessed by
measurement method A. |
|
E.2.2 | Secondary objectives of the trial |
• To compare CRD007 (10 mg, 25 mg and 40 mg tablets) to matching placebo tablets with
respect to efficacy in terms of change in maximum aortic diameter after 12 months of
treatment (b.i.d.) as assessed by measurement method B
• To compare CRD007 (10 mg, 25 mg and 40 mg tablets) to matching placebo tablets with
respect to efficacy in terms of change in maximum aortic diameter after 6 months of
treatment (b.i.d.) as assessed by both measurement method A and B
• To compare CRD007 (10 mg, 25 mg and 40 mg tablets) to matching placebo tablets with
respect to efficacy in terms of incidence and time to maximum aortic diameter of 50 mm
as assessed by measurement method A and B3
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Infrarenal abdominal aortic aneurysm with a maximum diameter between ≥39 mm and
≤49 mm4
2. Age ≥50 years
3. Following receipt of verbal and written information about the trial, the subject has
provided signed informed consent before any trial related activity is carried out |
|
E.4 | Principal exclusion criteria |
1. Previous infra-renal aortic surgery
2. Planned major surgery
3. Known aortic dissection
4. Known diabetes
5. Treatment with systemic corticosteroids or any other systemic immunomodulatory therapy
6. Known or suspected inherited connective tissue disorders (i.e. Marfan or Vascular Ehlers
Danlos syndrome)
7. Calculated CLCR < 30 ml/min5
8. Known significant liver disease (e.g. acute clinical hepatitis, chronic active hepatitis or
ALT >3 x the ULN6)
9. Known HIV infection at the time of screening
10. Serious concomitant illness associated with a life expectancy less than 2 years
11. Active severe infection, any other concurrent disease or medical conditions that are
deemed to interfere with the conduct of the trial as judged by the investigator
12. Clinically significant cardiac disease including unstable angina, acute myocardial
infarction within six months from screening and congestive heart failure (NYHA III-IV
according to the New York Heart Association (NYHA) functional classification system)
13. Significant concurrent, uncontrolled medical condition including, but not limited to, renal,
hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or
psychiatric disease evaluated by the investigator to interfere with effect of the trial drug
14. Subjects known or suspected of not being able to comply with this trial protocol (e.g. due
to alcoholism, drug dependency or psychological disorder)
15. Receipt of prior experimental agents within 30 days prior to screening
16. Current participation in any other interventional clinical trial
17. Subjects with known uncontrolled allergic conditions or allergy/hypersensitivity to any
component of the trial drug or placebo excipients |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Absolute change in maximum aortic diameter from screening (Visit 1) to 12 months of
treatment (Visit 7) as assessed by measurement method A. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary endpoint is evaluated after 12 months of treatment |
|
E.5.2 | Secondary end point(s) |
• Absolute change in maximum aortic diameter from screening (Visit 1) to 12 months of
treatment (Visit 7) as assessed by measurement method B3
• Absolute change in maximum aortic diameter from screening (Visit 1) to 6 months of
treatment (Visit 5) as assessed by both measurement method A and B3
• Incidence and time to maximum aortic diameter of 50 mm as assessed by measurement
method A and B3
• Incidence and time to clinical events of special interest
- Acute or elective aneurysm repair
- Aneurysm rupture
- Major cardiovascular events
- Other clinical events of special interest
- Death (any cause)
• Biomarkers
• Adverse events
• ECG assessments
• Blood pressure and pulse
• Haematology, serum chemistry and liver function parameters |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
•The evaluation of change in maximum aortic diameter after 6 and 12 months of treatment
• Incidencee and time to clinical event: any time during the treatment
• Biomarkers: after 12 months treatment
• Adverse events: at each clinical visit (week 1, 13, 26, 39 and 52 of treatment)
• ECG assessment: after 12 months treatment
• Blood pressure and pulse: at each clinical visit (week 1, 13, 26, 39 and 52 of treatment)
• Haematology, serum chemistry and liver function parameters: after 13, 26, 39 and 52 weeks treatment |
|
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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 16 |
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 | No |
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
|
The end of the trial is defined as the date of last subject last visit. |
|
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 | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |