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Completed

NCT Number: NCT03995784

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

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.

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Key information

Conditions

Hemophilia B Blood Coagulation Disorders Blood Coagulation Disorders, Inherited Coagulation Protein Disorders Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Genetic Diseases, X-Linked Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders

Age range

18 year and older

Sex eligibility

Male

Study type

Interventional

Phase

Phase 2

Primary location

Haemophilia Comprehensive Care Centre

Johannesburg, South Africa

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Coagulation Factor IX variant

Biological

Single intravenous injection of CB2679d/Dalcinonacog alfa

Primary outcomes

  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 outcomes

  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

Sponsors and collaborators

Lead sponsor

Catalyst Biosciences

Industry

Registry information

Official study 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

Important dates

Study start
2019
Primary completion
2020
Study completion
2020
First posted
Jun 24, 2019
Registry last updated
Aug 9, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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