E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Catheter Occlusion Thrombosis |
|
E.1.1.1 | Medical condition in easily understood language |
Restoration of function to central venous access devices (CVADs) |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
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 demonstrate the superiority of CUSA-081 compared to placebo in the rate of treatment success following a single administration with a dwell time up to 90 minutes. Treatment success is defined as restoration of CVAD functionality measured as the ability to withdraw 3 mL of blood and infuse 5 mL of saline. |
|
E.2.2 | Secondary objectives of the trial |
1. To demonstrate the non-inferiority of CUSA-081 compared to alteplase in the rate of treatment success following a single administration with a dwell time up to 90 minutes;
2. To demonstrate the superiority of CUSA-081 compared to placebo in the rate of treatment success following a single administration with a dwell time up to 60 minutes;
3. To demonstrate the superiority of CUSA-081 compared to placebo in the rate of treatment success following up to two administrations with a dwell time up to 180 minutes;
4. To demonstrate the superiority of CUSA-081 compared to alteplase in the rate of treatment success following a single administration with a dwell time up to 90 minutes;
5. To evaluate the safety and tolerability of CUSA-081;
6. To evaluate the rate of recurrent catheter dysfunction defined as first re-occlusion within 30 days following administration of CUSA-081. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Inability to have 3mL of blood withdrawn from the selected study
catheter;
2. A single or multi-lumen CVAD, implanted ports or peripherally inserted
central catheters (PICCs) in place for > 24 hours and documented as
previously being patent and functional;
3. Ability to designate one dysfunctional lumen of a multi-lumen catheter
to be used throughout the study for both study drug instillation and
assessment of CVAD function;
4. Male and non-pregnant female subjects 18 years or older;
5. Able to have fluids infused at the volume necessary to instill study
drug into the CVAD (i.e., up to 2 mL);
6. Informed consent form (ICF) signed and dated indicating that the
subject has been informed of and agreed with all pertinent aspects of
the study and is willing to comply with all study requirements and
procedures.
Note: TA urine pregnancy test is required for all females of childbearing
potential. Women in natural or surgical menopause do not need to be
tested for pregnancy. Natural menopause is defined as the permanent
cessation of menstrual periods, determined retrospectively after a
woman has experienced 12 consecutive months of lack of menstruation
(amenorrhea) without any other obvious pathological or physiological
cause. Surgical menopause is defined as the removal of both ovaries
(bilateral oophorectomy) before the natural menopause. |
|
E.4 | Principal exclusion criteria |
1. CVAD (any type) used for Hemodialysis;
2. CVAD known to be dysfunctional for more than 48 hours;
3. Reasonable evidence of mechanical or non-thrombotic occlusion in
the selected study catheter (e.g., catheter malposition or migration,
sutures, kinks, or precipitates causing obstruction), radiographic
assessment is not required;
4. Known or suspected catheter-related bloodstream infection (CRBSI);
5. Use of any intravenously administered fibrinolytic agent or
anticoagulant (For example, but not limited to, alteplase, tenecteplase,
reteplase, urokinase or heparin) within 24 hours prior to the treatment
period (first instillation of study drug). Use of subcutaneous LMWH, UFH
or heparinoids for prophylaxis of thromboembolic events is allowed.
Furthermore, the use of oral anticoagulants is allowed;
6. Known to be at high risk for bleeding events or embolic complications
in the opinion of the Investigator, or has a known condition for which
bleeding constitutes a significant hazard (e.g.
recent stroke, recent intracranial or intraspinal surgery or serious head
trauma, intracranial neoplasm, arteriovenous malformation or aneurysm,
known bleeding diathesis);
7. Uncontrolled hypertension (systolic BP ≥160 or diastolic BP ≥110
mmHg) at screening;
8. Clinically unstable in the opinion of the site investigator;
9. Known to be pregnant or breastfeeding at screening;
10. Previously treated in this study (READY 1) or in study READY 2;
11. History of allergic reaction to reteplase, alteplase or vial ingredients
(excipients or diluents);
12. Use of any investigational drug or experimental medical device
within 28 days prior to treatment; non interventional observational
studies participation is allowed;
13. Not mentally, socially or otherwise able to complete the trial
assessments or not likely to survive beyond 30 days. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of subjects who have treatment success following a single instillation of study drug (CUSA-081, placebo, or alteplase). Treatment success is defined as the restoration of CVAD functionality measured as the ability to withdraw 3 mL of blood and infuse 5 mL of saline. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1. Percentage of subjects who have treatment success following a single instillation of study drug .
2. Percentage of subjects who have treatment success after up to two instillations of study drug.
3. The rate of recurrent catheter dysfunction defined as first re-occlusion. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. 30 minutes, 60 minutes.
2. 120 minutes, 150 minutes, 180 minutes.
3. 30 days. |
|
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 | 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 | 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) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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 |
Brazil |
United States |
Belgium |
Poland |
Romania |
Spain |
Czechia |
Argentina |
|
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
|
Defined in the study protocol as the last 30-day (day 30 +/- 2 days) follow-up contact of the last subject who received study drug in the trial. |
|
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 | 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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |