Acquired Factor X Deficiency
Conditions
Keywords
Factor X Deficiency, Blood Coagulation Disorders, Hematologic Diseases, Hemorrhagic Disorders, Light Chain amyloidosis, AL amyloidosis
Brief summary
The purpose of this study is to evaluate the efficacy and safety of Coagadex in treating active bleeds and to manage peri-operative bleeding in participants with acquired factor X deficiency associated with AL amyloidosis.
Detailed description
This study is designed to evaluate the efficacy and safety of Coagadex® in treating active bleeds and to manage peri-operative bleeding in participants with aFXD associated with AL amyloidosis. Coagadex® is a plasma-derived human coagulation factor concentrate expected to treat bleeding episodes in patients with aFXD associated with AL amyloidosis by delivering concentrated Factor X to address the clotting deficiency caused by the disease. aFXD is a rare condition (prevalence of \<1 / 1 000 000 \[Orphanet 2024\]) and may occur due to infections, neoplastic and chronic diseases (Lee G et al., 2012). aFXD is considered severe when the FX coagulant activity (FX:C) level is \< 25% of normal (normal range 70 - 150 IU/dL), and moderate when FX:C level is 25% to 50% of normal (Choufani et al., 2001). AL amyloidosis is the most common cause of acquired FX Deficiency (aFXD). In AL amyloidosis, amyloid fibrils bind to and reduce the levels of circulating FX and shorten its half-life, causing aFXD, leading to an increase in risk of bleeding. Bleeding may occur both in patients with moderate and severe deficiency
Interventions
BIOLOGICALCoagadex(R)
Coagulation Factor X (Human)
Sponsors
Kedrion S.p.A.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
None (open label)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female participants ages 18-70 years old. 2. Diagnosis of aFXD associated with AL amyloidosis with FX:C ≤ 50 IU/dL. 3. Woman of Childbearing Potential (defined in Appendix 2) and men of reproductive potential who agree to use an effective contraception measure during the study.
Exclusion criteria
1. Female participants that are pregnant or lactating. 2. Presence of FX inhibitors. 3. Uncontrolled arterial hypertension. 4. On anticoagulant therapy (not antiplatelets), unstable heart disease, clinically significant thrombotic event in the past 180 days or any other condition that the Investigator believes is likely to interfere with evaluation of the study drug or with satisfactory conduct of the trial. 5. Any factor X containing product taken within 2 weeks of first Coagadex® administration. 6. Participation in another interventional clinical study with an investigational drug, biologic, or device within 30 days prior to screening. 7. Hemodynamically unstable due to any cause or even after blood transfusion, fluid resuscitation and pharmacologic or volume replacement pressor therapy. 8. Prior history of bleeding disorder other than aFXD.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of bleeding events responsive to Coagdex® therapy at 72 hours after initiation of treatment in the On-Demand Treatment Cohort | at 72 hours | Proportion of bleeding events with a 'positive' response. |
| Proportion of bleeding events responsive to Coagdex® therapy at 72 hours after initiation of treatment in the Surgery/Invasive Procedures Cohort | at 72 hours | Proportion of bleeding events with a 'fair, good, or excellent' response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of bleeding events responsive to Coagdex® therapy at Different Timepoints After 72 hours in the On- Demand Cohort | Day 4 to day 30 | Investigators will assess Coagadex® efficacy in the on-demand treatment cohort by looking at: -Percentage of responsive bleedings, -The ability to discontinue or reduce the dose and/or dosing frequency of Coagadex®. |
| To assess the safety of Coagadex® by number and percentage of infusion related AEs, SAEs, coded by MedDRA | Day 0 through study completion, an average of up to 6 months. | To assess the safety of Coagadex® in the on-demand treatment of bleeding and management of peri-operative/peri-procedural hemostasis in infusion related AEs and SAEs. AEs and SAEs will be evaluated following the first Coagadex® administration: assessment of seriousness, causality assessment; and incidence, frequency, and severity of AEs and incidence and frequency of SAEs. |
| Proportion of bleeding events responsive to Coagdex® therapy at Different Timepoints After 72 hours in Surgery/Invasive Procedures Cohort | Day 4 to Day 14 | Investigators will assess Coagadex® efficacy in the surgery/invasive procedures cohort by looking at: * The overall percentage of bleeding episodes successfully controlled, * The ability to discontinue or reduce the dose and/or dosing frequency of Coagadex®. |
| Coagadex® exposure | Day 1 to Day 30 | Assess the number of study drug exposure days (overall and per participant) and the Coagadex® exposure per event. |
| Assess Post-treatment FX Levels | Day 1 to Day 30 | Assess in the on-demand treatment cohort and surgery/invasive procedures cohort by FX:C IU/mL |
| Assess bleeds at other sites. | Last Coagadex® until study completion, an average of up to 6 months. | Description: Assessed in the surgery/invasive procedures cohort by looking at: Number of sites per participant including severity, duration, location, and cause. |
| Assess the pharmacokinetics(PK) of Coagadex® in peri-operative/peri-procedural hemostasis in Surgery/Invasive Procedures Cohort. | Day 0 pre-dose to Day 5 | To assess the pharmacokinetics(PK) of Coagadex® in peri-operative/peri-procedural hemostasis by PK parameter Maximum Plasma Concentration \[Cmax\] |
Contacts
STUDY_DIRECTORMirella Calcinai, MD
Medical Director, Clinical Development
Outcome results
None listed