E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Catheter Occlusion Thrombosis |
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E.1.1.1 | Medical condition in easily understood language |
Restoration of function to central venous access devices (CVADs) |
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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 | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10007648 |
E.1.2 | Term | Cardiovascular disease, unspecified |
E.1.2 | System Organ Class | 100000004849 |
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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 evaluate the safety of up to two instillations of CUSA-081 for restoration of function to central venous access devices (CVADs) |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the rate of treatment success at each of 6 planned time points following up to two instillations of CUSA-081 with a dwell time of up to 180 minutes (90 minutes after each instillation). 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. - To evaluate the rate of recurrent catheter dysfunction defined as first re-occlusion within 30 days following instillation of CUSA-081. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Inability to have 3 mL of blood withdrawn from the selected study catheter; - A single or multi-lumen CVAD, implanted ports or peripherally inserted central catheters (PICCs) in place for 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; - 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; - Male and non-pregnant female subjects at least 18 years or older (see note below); - Able to have fluids infused at the volume necessary to instill study drug into the CVAD (i.e., up to 2 mL); - 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: A urine pregnancy test is required for all females of childbearing potential. Women in natural post-menopause or permanently sterile 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. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. |
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E.4 | Principal exclusion criteria |
- CVAD (any type) used for Hemodialysis; - CVAD known to be dysfunctional for more than 48 hours; - 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 (e.g., alteplase, tenecteplase, reteplase, urokinase or heparin) within 24 hours prior to the treatment period (first instillation of study drug). Use of subcutaneous low molecular weight heparin (LMWH), unfractionated heparin (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 2) or in study READY1; 11. History of allergic reaction to reteplase 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 study participation is allowed; 13. Not mentally, socially or otherwise able to complete the trial assessments or not likely to survive beyond 30 days. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is the percentage of subjects who have treatment success following a single instillation of study drug (CUSA-081, alteplase, or placebo) with a dwell time up to 90 minutes. 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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
30, 60, and 90 minutes following a single instillation of study drug |
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E.5.2 | Secondary end point(s) |
1) Percentage of subjects who have treatment success following a single instillation of study drug with a total dwell time up to 30 and 60 minutes; 2) Percentage of subjects who have treatment success after up to two instillations of study drug with a total dwell time up to 120, 150 and 180 minutes; 3) Rate of recurrent catheter dysfunction (defined as first re-occlusion) within 30 days following treatment with study drug; 4) Treatment Emergent Adverse Events (TEAEs), Adverse Drug Reactions (ADRs), Serious Treatment Emergent Adverse Events (SAEs), serious related TEAEs, TEAEs leading to study withdrawal, and TEAEs leading to death; 5) Treatment Emergent Adverse Events of Special Interest (AESI).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) 30 and 60 minutes following a single instillation of study drug; 2) 120, 150, and 180 minutes following up to two instillations of study drug; 3) 30 days following completion of the treatment period; 4) Through the duration of the treatment period. Of note, post-treatment adverse events are also monitored during the 30 day follow-up period; 5) Through the duration of the treatment period. Of note, post-treatment adverse events of special interest are also monitored during the 30 day follow-up period.
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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 | 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 | 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
| 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 |
Bulgaria |
Hungary |
United States |
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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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The last 30-day (day 30 +/- 2 days) follow-up contact of the last subject who received study drug in 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 | 0 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |