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Study of Next-Generation Recombinant Factor IX Variant in Adult Subjects With Hemophilia B

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03995784
Recruitment Status : Completed
First Posted : June 24, 2019
Results First Posted : August 9, 2021
Last Update Posted : August 9, 2021
Sponsor:
Information provided by (Responsible Party):
Catalyst Biosciences

Brief Summary:
Phase 2b, single-center, open-label study designed to evaluate the pharmacokinetics, pharmacodynamics, efficacy and safety of subcutaneous (SC) prophylaxis treatment regimens with CB2679d in 6 adult, male subjects with severe congenital hemophilia B.

Condition or disease Intervention/treatment Phase
Hemophilia B Biological: Coagulation Factor IX variant Phase 2

Detailed Description:

Single-center, open-label Phase 2b study will evaluate the PK, PD, efficacy and safety parameters of SC prophylaxis treatment regimens with CB2679d in adult subjects with hemophilia B. The study will enroll and dose subcutaneously, a total of 6 adult male subjects with severe congenital hemophilia B.

During the Treatment Period, the subject will receive an IV dose of 50 IU/kg followed 35 ± 5 minutes later by a SC dose of 100 IU/kg. Daily SC doses of 100 IU/kg will be administered until Day 28 (28 total SC doses). On Day 1, PK, PD, and safety assessments will be done at pre-IV dose and repeated 35 (± 5) minutes later prior to the SC dose. Subsequent PK, PD and safety assessments will be performed pre-dose on days 2, 3, 7, 14, 21 and 28.

During the Washout Period, PK, PD, and safety assessments will be done on Days 29, 30, 31, 32 and 33. Daily FIX activity levels will be measured, unless FIX activity level is known to be < 5%, as measured by local laboratory.

An End of Study visit will occur 30 days (± 2 days) after the last dose of study drug.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 2b Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Efficacy and Safety of a Subcutaneous Prophylaxis Treatment Regimen of CB2679d, in Adult Subjects With Hemophilia B
Actual Study Start Date : June 18, 2019
Actual Primary Completion Date : February 28, 2020
Actual Study Completion Date : April 30, 2020


Arm Intervention/treatment
Experimental: Intravenous Dose
Coagulation Factor IX variant, 50 IU/kg by intravenous route
Biological: Coagulation Factor IX variant
Single intravenous injection of CB2679d/Dalcinonacog alfa

Experimental: Subcutaneous Dosing
Coagulation Factor IX variant, 100 IU/kg by subcutaneous route
Biological: Coagulation Factor IX variant
Daily subcutaneous injections of CB2679d/Dalcinonacog alfa for 28 days




Primary Outcome Measures :
  1. Number of Subjects Who Achieved FIX Level ≥12% [ Time Frame: Days 7, 14, 21, 28, 29 ]
    Subjects who achieved a FIX activity level ≥12% during the treatment period in the PK Population


Secondary Outcome Measures :
  1. FIX Activity Levels (Actual and Change From Baseline) in All Subjects [ Time Frame: Screening, Day 1 (IV Pre-dose, SC Dose), Day 2, 3, 7, 14, 21, 28, 29, 30, 31, 32, 33, and End of Study. End of Study is the average of each subject's last recorded assessment (between Days 29 to 33). ]

    FIX Activity Levels measured by percent activity.

    Baseline was defined as the lowest assessment before the first administration of study drug. Maximum change from baseline was calculated as the maximum of the changes from baseline over all visits during treatment period. FIX activity level below the limit of quantification (BLQ) were set to zero. In case of retest, the average of the different test results were considered for the summary analyses.

    1 subject received a higher IV dose than allowed per protocol (150 IU/kg) at Day 1 thus this subject's values at Day 1 (SC Dose), Day 2, & Day 3 were excluded from this analysis & the total number of participants was lowered by 1 at these timepoints. Additionally, mean (standard deviation) for the maximum change from baseline in the FIX activity level (%) during SC dosing was calculated by excluding actual values at Day 1 IV dose, Day 1 SC dose, Day 2 & Day 3 for all 6 subjects.


  2. Pharmacokinetic (PK) Analysis - AUC [ Time Frame: From date of first dose of CB2679d until date of first occurrence of clinical event, assessed up to treatment Day 28. PK sampling was conducted on Day 1 (IV pre-dose -5 min, SC 30 min post IV dose, hour 7 +/- 1 hour) and Day 2 (hour 24 +/- 1 hour). ]
    Summary of Pharmacokinetic Parameters - AUC Infinity Observation and AUC to Last Non-zero Concentration

  3. PK Analysis - Clearance [ Time Frame: From date of first dose of CB2679d until date of first occurrence of clinical event, assessed up to treatment Day 28. PK sampling was conducted on Day 1 (IV pre-dose -5 min, SC 30 min post IV dose, hour 7 +/- 1 hour) and Day 2 (hour 24 +/- 1 hour). ]
    Summary of PK Parameters - Clearance

  4. PK Analysis - Maximum Concentration During SC Dosing [ Time Frame: From date of first dose of CB2679d until date of first occurrence of clinical event, assessed up to treatment Day 28. PK sampling was conducted on Day 1 (IV pre-dose -5 min, SC 30 min post IV dose, hour 7 +/- 1 hour) and Day 2 (hour 24 +/- 1 hour). ]
    Summary of PK Parameters - Maximum Concentration during SC dosing

  5. PK Analysis - Half-Life and Residence Time [ Time Frame: From date of first dose of CB2679d until date of first occurrence of clinical event, assessed up to treatment Day 28. PK sampling was conducted on Day 1 (IV pre-dose -5 min, SC 30 min post IV dose, hour 7 +/- 1 hour) and Day 2 (hour 24 +/- 1 hour). ]
    Summary of PK Parameters - Half-Life-1(alpha), Half-Life-1(beta), and Mean Residence Time

  6. PK Analysis - Volume of Distribution at Steady-State Observed [ Time Frame: From date of first dose of CB2679d until date of first occurrence of clinical event, assessed up to treatment Day 28. PK sampling was conducted on Day 1 (IV pre-dose -5 min, SC 30 min post IV dose, hour 7 +/- 1 hour) and Day 2 (hour 24 +/- 1 hour). ]
    Summary of PK Parameters - Volume of Distribution at Steady-State Observed

  7. Occurrence of Clinical Thrombotic Event [ Time Frame: From date of first dose of CB2679d until date of first occurrence of clinical event, assessed up to treatment Day 28 ]
    Rate of occurrence of clinical thrombotic event not attributable to another cause

  8. Occurrence of an Antibody Response [ Time Frame: From date of first dose of CB2679d until date of first occurrence of clinical event, assessed up to treatment Day 28 ]
    Rate of occurrence of an antibody response to CB2679d and cross-reactive with wild-type recombinant coagulation FIX

  9. Thrombogenicity Assessment - Fibrinogen [ Time Frame: Screening, Day 1 (IV Pre-dose, SC Dose), Day 2, 3, 7, 14, 21, 28, 29, 30, 31, 32, 33, and End of Study. End of Study is the average of each subject's last recorded assessment (between Days 29 to 33). ]
    Evaluation of the levels of thrombogenicity markers of a subcutaneous regimen of CB2679d

  10. Thrombogenicity Assessment - D-Dimer [ Time Frame: Screening, Day 1 (IV Pre-dose, SC Dose), Day 2, 3, 7, 14, 21, 28, 29, 30, 31, 32, 33, and End of Study. End of Study is the average of each subject's last recorded assessment (between Days 29 to 33). ]
    Evaluation of the levels of thrombogenicity markers of a subcutaneous regimen of CB2679d

  11. Thrombogenicity Assessment - Prothrombin Fragments 1 + 2 [ Time Frame: Screening, Day 1 (IV Pre-dose, SC Dose), Day 2, 3, 7, 14, 21, 28, 29, 30, 31, 32, 33, and End of Study. End of Study is the average of each subject's last recorded assessment (between Days 29 to 33). ]
    Evaluation of the levels of thrombogenicity markers of a subcutaneous regimen of CB2679d

  12. Thrombogenicity Assessment - Thrombin/Antithrombin [ Time Frame: Screening, Day 1 (IV Pre-dose, SC Dose), Day 2, 3, 7, 14, 21, 28, 29, 30, 31, 32, 33, and End of Study. End of Study is the average of each subject's last recorded assessment (between Days 29 to 33). ]
    Evaluation of the levels of thrombogenicity markers of a subcutaneous regimen of CB2679d



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of severe (<2%) congenital hemophilia B.
  • Male, age 18 or older.
  • Agreement to use highly effective birth control throughout the study.
  • Affirmation of informed consent with signature confirmation before any trial-related activities.
  • Stated willingness to comply with all study procedures and availability for the duration of the study.

Exclusion Criteria:

  • History or a family history of FIX inhibitors.
  • Positive antibody to FIX detected by central laboratory at screening.
  • Previous participation in and subsequent treatment in a clinical trial within the previous 30 days or 3-half-lives, whichever is longer, or absence of clinical effect.
  • Have a coagulation disorder other than congenital hemophilia B.
  • Factor IX gene mutation 128G>A.
  • Significant contraindication to participation.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03995784


Locations
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South Africa
Haemophilia Comprehensive Care Centre
Johannesburg, South Africa
Sponsors and Collaborators
Catalyst Biosciences
Investigators
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Study Director: Howard Levy, MD, PhD, MMM Catalyst Biosciences
  Study Documents (Full-Text)

Documents provided by Catalyst Biosciences:
Study Protocol  [PDF] October 17, 2018
Statistical Analysis Plan  [PDF] July 14, 2020

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Responsible Party: Catalyst Biosciences
ClinicalTrials.gov Identifier: NCT03995784    
Other Study ID Numbers: DLZ-201
First Posted: June 24, 2019    Key Record Dates
Results First Posted: August 9, 2021
Last Update Posted: August 9, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: This is a single-center, open label study so the investigator will have full access to all study subject data.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hemophilia A
Hemophilia B
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked