FIB Grifols Congenital Deficiency for On-demand Treatment and Surgical Prophylaxis

• ClinicalTrials.gov Identifier: NCT04636268
• Recruitment Status: Suspended
• First Posted: November 19, 2020
• Last Update Posted: May 13, 2021
• Sponsor: Instituto Grifols, S.A.
• Information provided by (Responsible Party): Grifols Therapeutics LLC ( Instituto Grifols, S.A. )

Study Description

Brief Summary:

This is a phase 3, multi-center, prospective, open-label, single-arm, clinical trial to be carried out in subjects with congenital fibrinogen deficiency manifested as afibrinogenemia or severe hypofibrinogenemia.

This clinical trial is planned to be performed at study sites in multiple countries. It is planned to include a maximum of 32 adult and pediatric subjects with congenital fibrinogen deficiency in order to provide at least 28 evaluable acute bleeding episodes and/or surgical procedures.

Condition or disease	Intervention/treatment	Phase
Congenital Afibrinogenemia; Hypofibrinogenemia	Biological: FIB Grifols	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 32 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective, Multicenter, Open-label, Single-arm Study to Evaluate the Efficacy and Safety of Human Plasma-derived Fibrinogen Concentrate (FIB Grifols) in Subjects With Congenital Afibrinogenaemia and Severe Hypofibrinogenemia Requiring Either On-demand Treatment for Acute Bleeding or Surgical Prophylaxis
• Estimated Study Start Date: March 2022
• Estimated Primary Completion Date: June 30, 2023
• Estimated Study Completion Date: December 31, 2023

Arms and Interventions

Arm

Intervention/treatment

Experimental: FIB Grifols; FIB Grifols is the IP and will be administered via slow intravenous (IV) infusion at a rate not to exceed 5 mL/minute. Dosing will be individually calculated for each subject based on the target plasma fibrinogen level according to the type of bleeding, measured actual plasma fibrinogen level before infusion, and body weight. The IP will be administered according to the nominal potency of the product.

Biological: FIB Grifols; FIB Grifols is the IP and will be administered via slow intravenous (IV) infusion at a rate not to exceed 5 mL/minute. Dosing will be individually calculated for each subject based on the target plasma fibrinogen level according to the type of bleeding, measured actual plasma fibrinogen level before infusion, and body weight. The IP will be administered according to the nominal potency of the product.; Other Name: Fibrinogen

Outcome Measures

Primary Outcome Measures :

1. Hemostatic efficacy of FIB Grifols in on-demand treatment of all documented acute bleeding episodes as assessed by the Independent Endpoint Adjudication Committee (IEAC) Using a 4-Point Scale [ Time Frame: Up to Day 7 ]
   To clinically evaluate the hemostatic efficacy of FIB Grifols in on-demand treatment of all documented acute bleeding episodes in subjects with congenital fibrinogen deficiency as determined by the the proportion of successful treatment responses (Yes/No) indicated by a hemostatic efficacy rating of "Excellent" or "Good" as assessed by the IEAC using a 4 point scale. Hemostatic efficacy will be determined at end of treatment observation period (either at Day 3 for non-life threatening bleeding episodes, at Day 7 for life-threatening bleeding episodes, or at 24 hours after the end of the last infusion of FIB Grifols, whichever is later).
2. Hemostatic efficacy of FIB Grifols in perioperative management of bleeding during and after all documented surgical procedures as assessed by the IEAC Using a 4-Point Scale [ Time Frame: Up to Day 7 ]
   To clinically evaluate the hemostatic efficacy of FIB Grifols in the perioperative management of bleeding during and after all documented surgical procedures in subjects with congenital fibrinogen deficiency as determined by the the proportion of successful treatment responses (Yes/No) indicate by an adjudicated hemostatic efficacy rating of "Success" in preventing excessive bleeding during and after all documented surgical procedures as assessed by the IEAC using a 4 point scale. Hemostatic efficacy will be determined at end of treatment observation period (either at Day 3 for minor surgical procedures, at Day 7 for major surgical procedures, or at 24 hours after the end of the last infusion of FIB Grifols, whichever is later).

Secondary Outcome Measures :

1. Hemostatic Efficacy of FIB Grifols in Treating the First Documented Acute Bleeding Episode as Assessed by the IEAC Using a 4-Point Scale. [ Time Frame: Up to Day 7 ]

   Overall clinical assessment of the hemostatic efficacy of FIB Grifols in treating the first documented acute bleeding episode using a 4-point hemostatic efficacy scale including the four items: 'excellent,' 'good,' moderate,' and 'none'. These data will be transformed into a dichotomous result, with 'treatment success-yes' defined as a rating of 'excellent' or 'good' and 'treatment success-no' defined as a rating of 'moderate' or 'none'. This secondary efficacy endpoint will be assessed by the IEAC.

   Hemostatic efficacy will be determined at end of treatment observation period (either at Day 3 for non-life threatening bleeding episodes, at Day 7 for life-threatening bleeding episodes, or at 24 hours after the end of the last infusion of FIB Grifols, whichever is later).

2. Hemostatic Efficacy of FIB Grifols in Preventing Excessive Bleeding During and After the First Documented Surgical Procedure as Assessed by the IEAC Using a 4-Point Scale [ Time Frame: Up to Day 7 ]

   Overall clinical assessment of the hemostatic efficacy of FIB Grifols in preventing excessive bleeding during and after the first documented surgical procedure using a 4-point hemostatic efficacy scale including the four items: 'excellent,' 'good,' moderate,' and 'none'. These data will be transformed into a dichotomous result, with 'treatment success-yes' defined as a rating of 'excellent' or 'good' and 'treatment success-no' defined as a rating of 'moderate' or 'none'. This secondary efficacy endpoint will be assessed by the IEAC.

   Hemostatic efficacy will be determined at end of treatment observation period (either at Day 3 for minor surgical procedures, at Day 7 for major surgical procedures, or at 24 hours after the end of the last infusion of FIB Grifols, whichever is later).

3. Hemostatic Efficacy of FIB Grifols in Treating the First Acute Bleeding Episode [ Time Frame: Up to Day 7 ]

   Overall clinical assessment of the hemostatic efficacy of FIB Grifols in treating the first acute bleeding episode as assessed by the principal investigator at each trial site using a 4-point hemostatic efficacy scale including the four items: 'excellent,' 'good,' moderate,' and 'none'. These data will be transformed into a dichotomous result, with 'treatment success-yes' defined as a rating of 'excellent' or 'good' and 'treatment success-no' defined as a rating of 'moderate' or 'none'.

   Hemostatic efficacy will be determined at end of treatment observation period (either at Day 3 for non-life threatening bleeding episodes, at Day 7 for life-threatening bleeding episodes, or at 24 hours after the end of the last infusion of FIB Grifols, whichever is later).

4. Hemostatic Efficacy of FIB Grifols in Treating All Acute Bleeding Episodes [ Time Frame: Up to Day 7 ]

   Overall clinical assessment of the hemostatic efficacy of FIB Grifols in treating all acute bleeding episodes as assessed by the principal investigator at each trial site using a 4-point hemostatic efficacy scale including the four items: 'excellent,' 'good,' moderate,' and 'none'. These data will be transformed into a dichotomous result, with 'treatment success-yes' defined as a rating of 'excellent' or 'good' and 'treatment success-no' defined as a rating of 'moderate' or 'none'.

   Hemostatic efficacy will be determined at end of treatment observation period (either at Day 3 for non-life threatening bleeding episodes, at Day 7 for life-threatening bleeding episodes, or at 24 hours after the end of the last infusion of FIB Grifols, whichever is later).

5. Hemostatic Efficacy of FIB Grifols in Preventing Excessive Bleeding Intra-operatively for All Surgical Procedures. [ Time Frame: Up to Day 7 ]

   Clinical assessment of the hemostatic efficacy of FIB Grifols in preventing excessive bleeding intra-operatively for all surgical procedures as assessed by the surgeon (defined as the licensed medical professional performing the invasive procedure [eg, dentist]) using a 4-point hemostatic efficacy scale including the four items: 'excellent,' 'good,' moderate,' and 'none'. These data will be transformed into a dichotomous result, with 'treatment success-yes' defined as a rating of 'excellent' or 'good' and 'treatment success-no' defined as a rating of 'moderate' or 'none'.

   Hemostatic efficacy will be determined at end of treatment observation period (either at Day 3 for minor surgical procedures, at Day 7 for major surgical procedures, or at 24 hours after the end of the last infusion of FIB Grifols, whichever is later).

6. Hemostatic Efficacy of FIB Grifols in Preventing Excessive Bleeding After All Surgical Procedures (ie, Post-operative) [ Time Frame: Up to Day 7 ]

   Clinical assessment of the hemostatic efficacy of FIB Grifols in preventing excessive bleeding after all surgical procedures (ie, post-operative) as assessed by the principal investigator at each trial site using a 4-point hemostatic efficacy scale including the four items: 'excellent,' 'good,' moderate,' and 'none'. These data will be transformed into a dichotomous result, with 'treatment success-yes' defined as a rating of 'excellent' or 'good' and 'treatment success-no' defined as a rating of 'moderate' or 'none'.

   Hemostatic efficacy will be determined at end of treatment observation period (either at Day 3 for minor surgical procedures, at Day 7 for major surgical procedures, or at 24 hours after the end of the last infusion of FIB Grifols, whichever is later).

Eligibility Criteria

• Ages Eligible for Study: 6 Years to 70 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Male or female subject between 6 to 70 years of age.
2. Signed and dated written ICF, or the subject's parent or legal guardian signs and dates the ICF where applicable, and the Subject Authorization Form (SAF) where applicable. Pediatric subjects, as defined by local regulations, will be asked to sign an age appropriate assent form.
3. Diagnosed with congenital fibrinogen deficiency manifested as afibrinogenemia or severe hypofibrinogenemia (fibrinogen <50 mg/dL) and expected to require treatment for acute bleeding (either spontaneous or after trauma [defined as any accidental event leading to acute bleeding]), or prophylaxis of bleeding before a surgical intervention or invasive procedure.
4. Fibrinogen level < 50 mg/dL determined by Clauss method at baseline (sample drawn within 24 hours prior to infusion on Infusion 1 Day 1 Visit).
5. Female subjects of child-bearing potential must have a negative test for pregnancy blood or urine human chorionic gonadotropin (HCG)-based assay at baseline (sample drawn within 24 hours prior to infusion on Infusion 1 Day 1 Visit).
6. Willing to comply with all aspects of the clinical trial protocol, including blood sampling, for the entire duration of the study.

Exclusion Criteria:

1. Has acquired (secondary) fibrinogen deficiency.
2. Diagnosed with dysfibrinogenemia.
3. Has known antibodies against fibrinogen.
4. Has history of anaphylaxis or severe systemic response to any drug or blood-derived product.
5. Has history of intolerance to any component of the IP.
6. Documented history of immunoglobulin A (IgA) deficiency and antibodies against IgA.
7. Is a female who is pregnant, breastfeeding or, if of child-bearing potential, unwilling to practice a highly effective method of contraception (eg, oral, injectable, or implantable hormonal methods of contraception, placement of an IUD or intrauterine system, condom or occlusive cap with spermicidal foam/gel/film/cream/suppository, male sterilization, or true abstinancea) throughout the study.
8. Has any medical condition which is likely to interfere with the evaluation of the IP and/or the satisfactory conduct of the clinical trial according to the investigator's judgment.
9. Has congenital or acquired bleeding disorders other than congenital fibrinogen deficiency.
10. Has life expectancy of less than 6 months.
11. Received FRT within 21 days prior to the Screening Visit.
12. Receiving, or having received within 3 months prior to the Screening Visit of this clinical trial, any investigational drug or device.
13. Is unlikely to adhere the protocol requirements, or is likely to be uncooperative, or unable to provide a storage sample prior to IP infusion.

Contacts and Locations

Locations

United States, New York

Northwell Health HTC-LIJ Medical Center

New Hyde Park, New York, United States, 11040

Bulgaria

Spetsializirana Bolnitsa za Aktivno Lechenie na Hematologich

Sofia, Bulgaria, 1756

India

Victoria Hospital Bangalore Medical College and Research Institute - Hematology

Bangalore, India, 560002

St. John's Medical College Hospital

Bangalore, India, 560034

Advanced Medicare & Research Institute Ltd. (AMRI) Hospitals

Kolkata, India, 700098

Sahyadri Specialty Hospital

Pune, India, 411038

Nirmal Hospital

Surat, India, 395002

Lebanon

Hotel Dieu de France Hospital

Beirut, Lebanon

Turkey

Ege Universitesi Tip Fakultesi - Hematology

İzmir, Turkey, 35040

Erciyes University Medical Faculty

Kayseri, Turkey, 38039

Sponsors and Collaborators

Instituto Grifols, S.A.

More Information

• Responsible Party: Instituto Grifols, S.A.
• ClinicalTrials.gov Identifier: NCT04636268
• Other Study ID Numbers: GC1801; 2018-004005-81 ( EudraCT Number )
• First Posted: November 19, 2020
• Last Update Posted: May 13, 2021
• Last Verified: February 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Afibrinogenemia; Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn