Efficacy and Safety of CUSA-081 in the Restoration of Dysfunctional Central Venous Access Device (CVAD) Functionality

NCT03992443 | Withdrawn Phase 3 FDA Drug

• 2 other identifiers: CUSA-081-HEM-022021-004026-30
• Study Type: interventional
• Target: N/A
• Locations: 3 countries
• Sites: 15

Brief Summary

Study to evaluate the efficacy and safety of CUSA-081 in the restoration of central venous access device (CVAD) functionality in participants 12 years and older.

Conditions

Restoration of Function to CVADs

Keywords

CVAD; CUSA-081; reteplase

Outcome Measures

Primary Outcomes (1)

• Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs)

  TEAEs were defined as any adverse event (AE) with a start date on or after administration of the study drug (on Day 1). A severe AE was defined as an AE that was incapacitating and required medical intervention. The number of participants who experienced 1 or more severe TEAEs after dosing on Day 1 through the Follow-up Visit (Day 30) is presented. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module.

  Day 1 (postdose) through Day 30

Secondary Outcomes (2)

• Percentage Of Participants Who Had Treatment Success Following A Single Instillation Of Study Drug With A Dwell Time Up To 90 Minutes

  Day 1 (up to 90 mins postdose)

• Rate Of Recurrent Catheter Dysfunction Within 30 Days Following Treatment With Study Drug

  Day 1 (postdose) up to Day 30

Study Arms (1)

CUSA-081

EXPERIMENTAL

Participants received 1 or 2 doses of CUSA-081, 0.70 milligrams (mg) per 2 milliliter (mL) directly into the catheter lumen. Participants received the first dose at minute (min) 0, and the second dose, if needed, at min 90. Assessments were performed at min 30, 60, 90, 120, 150, and 180.

Drug: CUSA-081

Interventions

CUSA-081 DRUG

Participants received 1 or 2 doses of CUSA-081, 0.70 mg/2 mL, directly into the catheter lumen

Also known as: reteplase

CUSA-081

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Inability to have 3 mL of blood withdrawn from the selected study catheter;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.

You may not qualify if:

• 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;
• Known or suspected catheter-related bloodstream infection (CRBSI);
• 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.
• 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);
• Uncontrolled hypertension (systolic BP ≥160 or diastolic BP ≥110 mmHg) at screening;
• Clinically unstable in the opinion of the site investigator;
• Known to be pregnant or breastfeeding at screening;
• Previously treated in this study (READY 2) or in study READY 1;
• History of allergic reaction to reteplase or vial ingredients (excipients or diluents);
• Use of any investigational drug or experimental medical device within 28 days prior to treatment; non interventional observational study participation is allowed;
• Not mentally, socially or otherwise able to complete the trial assessments or not likely to survive beyond 30 days.

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead

Study Sites (15)

Chiesi investigational site

San Luis Obispo, California, 93401, United States

Location

Chiesi Investigational site

Torrance, California, 90501, United States

Location

Chiesi Investigational site

Tampa, Florida, 33601, United States

Location

Chiesi investigation site

Greenville, North Carolina, 80015, United States

Location

Chiesi Investigational site

Huntersville, North Carolina, 28070, United States

Location

Chiesi Investigational site

Dayton, Ohio, 45390, United States

Location

Chiesi investigational site

Ohio City, Ohio, 44701, United States

Location

Chiesi investigational site

Pleven, Bulgaria

Location

Chiesi Investigational site

Plovdiv, Bulgaria

Location

Chiesi Investigational Site

Razgrad, Bulgaria

Location

Chiesi Investigational site

Sofia, Bulgaria

Location

Chiesi Investigational site

Stara Zagora, Bulgaria

Location

Chiesi investigational site

Budapest, Hungary

Location

Chiesi investigational site

Kecskemét, Hungary

Location

Chiesi investigational site

Székesfehérvár, Hungary

Location

MeSH Terms

Interventions

reteplase

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2019
• First Posted: June 20, 2019
• Study Start: February 28, 2022
• Primary Completion: March 18, 2022
• Study Completion: March 18, 2022
• Last Updated: April 15, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

BU (5); US (7); HU (3)