- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03995784
Study of Next-Generation Recombinant Factor IX Variant in Adult Subjects With Hemophilia B
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
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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-
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Johannesburg, South Africa
- Haemophilia Comprehensive Care Centre
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Intravenous Dose
Coagulation Factor IX variant, 50 IU/kg by intravenous route
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Single intravenous injection of CB2679d/Dalcinonacog alfa
Daily subcutaneous injections of CB2679d/Dalcinonacog alfa for 28 days
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Experimental: Subcutaneous Dosing
Coagulation Factor IX variant, 100 IU/kg by subcutaneous route
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Single intravenous injection of CB2679d/Dalcinonacog alfa
Daily subcutaneous injections of CB2679d/Dalcinonacog alfa for 28 days
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Subjects Who Achieved FIX Level ≥12%
Time Frame: Days 7, 14, 21, 28, 29
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Subjects who achieved a FIX activity level ≥12% during the treatment period in the PK Population
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Days 7, 14, 21, 28, 29
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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. |
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).
|
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
|
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).
|
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
|
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).
|
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).
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Summary of PK Parameters - Maximum Concentration during SC dosing
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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).
|
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).
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Summary of PK Parameters - Half-Life-1(alpha), Half-Life-1(beta), and Mean Residence Time
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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).
|
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).
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Summary of PK Parameters - Volume of Distribution at Steady-State Observed
|
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).
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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
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Rate of occurrence of clinical thrombotic event not attributable to another cause
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From date of first dose of CB2679d until date of first occurrence of clinical event, assessed up to treatment Day 28
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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
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Rate of occurrence of an antibody response to CB2679d and cross-reactive with wild-type recombinant coagulation FIX
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From date of first dose of CB2679d until date of first occurrence of clinical event, assessed up to treatment Day 28
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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).
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Evaluation of the levels of thrombogenicity markers of a subcutaneous regimen of CB2679d
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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).
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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).
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Evaluation of the levels of thrombogenicity markers of a subcutaneous regimen of CB2679d
|
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).
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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).
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Evaluation of the levels of thrombogenicity markers of a subcutaneous regimen of CB2679d
|
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).
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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).
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Evaluation of the levels of thrombogenicity markers of a subcutaneous regimen of CB2679d
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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).
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Howard Levy, MD, PhD, MMM, Catalyst Biosciences
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- DLZ-201
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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