Clinical trial NCT03995784: Study of Next-Generation Recombinant Factor IX Variant in Adult Subjects With Hemophilia B
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hemophilia B
Lead sponsor: Catalyst Biosciences
Sponsor class: INDUSTRY
First posted: 2019-06-24
Enrollment: 6
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Number of Subjects Who Achieved FIX Level ≥12%
timeFrame: Days 7, 14, 21, 28, 29
Secondary outcomes:
measure: FIX Activity Levels (Actual and Change From Baseline) in All Subjects
timeFrame: 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).
measure: Pharmacokinetic (PK) Analysis - AUC
timeFrame: 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).
measure: PK Analysis - Clearance
timeFrame: 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).
measure: PK Analysis - Maximum Concentration During SC Dosing
timeFrame: 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).
measure: PK Analysis - Half-Life and Residence Time
timeFrame: 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).
measure: PK Analysis - Volume of Distribution at Steady-State Observed
timeFrame: 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).
measure: Occurrence of Clinical Thrombotic Event
timeFrame: From date of first dose of CB2679d until date of first occurrence of clinical event, assessed up to treatment Day 28
measure: Occurrence of an Antibody Response
timeFrame: From date of first dose of CB2679d until date of first occurrence of clinical event, assessed up to treatment Day 28
measure: Thrombogenicity Assessment - Fibrinogen
timeFrame: 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).
measure: Thrombogenicity Assessment - D-Dimer
timeFrame: 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).
measure: Thrombogenicity Assessment - Prothrombin Fragments 1 + 2
timeFrame: 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).
measure: Thrombogenicity Assessment - Thrombin/Antithrombin
timeFrame: 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).
Other outcomes:
Locations:
city: Johannesburg
country: South Africa
facility: Haemophilia Comprehensive Care Centre
Study officials:
affiliation: Catalyst Biosciences
name: Howard Levy, MD, PhD, MMM
role: STUDY_DIRECTOR
References: