Hemophilia BPhase 2NCT03995784
Study of Next-Generation Recombinant Factor IX Variant in Adult Subjects With Hemophilia B
A Phase 2 study testing Coagulation Factor IX variant in people with Hemophilia B, run by Catalyst Biosciences at 1 site in South Africa.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Hemophilia B
- What is being tested?
- Coagulation Factor IX variant
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteSouth Africa
- Study dates
- 18 Jun 2019to 30 Apr 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Hemophilia B
- Being tested
- Coagulation Factor IX variant
- Medical subject headings
- Hemophilia B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Coagulation Factor IX variantBiological
Single intravenous injection of CB2679d/Dalcinonacog alfa
Coagulation Factor IX variantBiological
Daily subcutaneous injections of CB2679d/Dalcinonacog alfa for 28 days
| Study group | Role | What they receive |
|---|---|---|
| Intravenous Dose | Experimental | Coagulation Factor IX variant, 50 IU/kg by intravenous route Receives: Biological: Coagulation Factor IX variant |
| Subcutaneous Dosing | Experimental | Coagulation Factor IX variant, 100 IU/kg by subcutaneous route Receives: Biological: Coagulation Factor IX variant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects Who Achieved FIX Level ≥12%
Subjects who achieved a FIX activity level ≥12% during the treatment period in the PK Population
Measured: Days 7, 14, 21, 28, 29
Secondary outcomes (12)
FIX Activity Levels (Actual and Change From Baseline) in All Subjects
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.
Measured: 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
Summary of Pharmacokinetic Parameters - AUC Infinity Observation and AUC to Last Non-zero Concentration
Measured: 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
Summary of PK Parameters - Clearance
Measured: 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
Summary of PK Parameters - Maximum Concentration during SC dosing
Measured: 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
Summary of PK Parameters - Half-Life-1(alpha), Half-Life-1(beta), and Mean Residence Time
Measured: 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
Summary of PK Parameters - Volume of Distribution at Steady-State Observed
Measured: 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).
Occurrence of Clinical Thrombotic Event
Rate of occurrence of clinical thrombotic event not attributable to another cause
Measured: From date of first dose of CB2679d until date of first occurrence of clinical event, assessed up to treatment Day 28
Occurrence of an Antibody Response
Rate of occurrence of an antibody response to CB2679d and cross-reactive with wild-type recombinant coagulation FIX
Measured: From date of first dose of CB2679d until date of first occurrence of clinical event, assessed up to treatment Day 28
Thrombogenicity Assessment - Fibrinogen
Evaluation of the levels of thrombogenicity markers of a subcutaneous regimen of CB2679d
Measured: 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).
Thrombogenicity Assessment - D-Dimer
Evaluation of the levels of thrombogenicity markers of a subcutaneous regimen of CB2679d
Measured: 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).
Thrombogenicity Assessment - Prothrombin Fragments 1 + 2
Evaluation of the levels of thrombogenicity markers of a subcutaneous regimen of CB2679d
Measured: 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).
Thrombogenicity Assessment - Thrombin/Antithrombin
Evaluation of the levels of thrombogenicity markers of a subcutaneous regimen of CB2679d
Measured: 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).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2019
- Study start18 Jun 2019
- Primary completion28 Feb 2020
- Study completion30 Apr 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hemophilia BStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Catalyst Biosciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Howard Levy, MD, PhD, MMM, Study director, Catalyst Biosciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03995784
- Sponsor's protocol ID
- DLZ-201
- Status last verified
- Aug 2021
- First submitted
- 19 Jun 2019
- Last updated
- 9 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: This is a single-center, open label study so the investigator will have full access to all study subject data.
Publications
Faraj A, Le Moan N, Gorina E, Blouse GE, Knudsen T, Simonsson USH. Model-Informed Support of Dose Selection for Prophylactic Treatment with Dalcinonacog Alfa in Adult and Paediatric Hemophilia B Patients. Adv Ther. 2023 Sep;40(9):3739-3750. doi: 10.1007/s12325-023-02570-6. Epub 2023 Jun 21.
PubMed 37341915
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03995784
- Acronym / sponsor ID
- DLZ-201
- Conditions
- Hemophilia B
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Catalyst BiosciencesIndustry (pharma, biotech, devices)
- Study start
- 18 Jun 2019 (actual)
- Primary completion
- 28 Feb 2020 (actual)
- Study completion
- 30 Apr 2020 (actual)
- First posted
- 24 Jun 2019 (actual)
- Results
- Posted 9 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intravenous Dose | Experimental | Biological: Coagulation Factor IX variantCoagulation Factor IX variant, 50 IU/kg by intravenous route |
| Subcutaneous Dosing | Experimental | Biological: Coagulation Factor IX variantCoagulation Factor IX variant, 100 IU/kg by subcutaneous route |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Coagulation Factor IX variantSingle intravenous injection of CB2679d/Dalcinonacog alfa | Biological | Intravenous Dose |
| Coagulation Factor IX variantDaily subcutaneous injections of CB2679d/Dalcinonacog alfa for 28 days | Biological | Subcutaneous Dosing |
Primary outcome
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
12 secondary outcomes
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).
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).
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).
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).
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).
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).
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
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
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).
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).
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).
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).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37341915Faraj A, Le Moan N, Gorina E, Blouse GE, Knudsen T, Simonsson USH. Model-Informed Support of Dose Selection for Prophylactic Treatment with Dalcinonacog Alfa in Adult and Paediatric Hemophilia B Patients. Adv Ther. 2023 Sep;40(9):3739-3750. doi: 10.1007/s12325-023-02570-6. Epub 2023 Jun 21.
- Individual participant dataSharing planned: No. This is a single-center, open label study so the investigator will have full access to all study subject data.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Howard Levy, MD, PhD, MMM study director
Catalyst Biosciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Coagulation Factor IX variant in people with Hemophilia B, run by Catalyst Biosciences at 1 site in South Africa.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Subjects Who Achieved FIX Level ≥12% (time frame: Days 7, 14, 21, 28, 29). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03995784, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Aug 2021.