Severe Hemophilia APhase 1NCT04864743

A Study to Evaluate the Pharmacokinetics，Safety and Tolerability of PEG Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection

A Phase 1 study testing ADVATE and FRSW117 in people with Severe Hemophilia A, run by Hangzhou Gensciences Biopharmaceutical Co., Ltd. at 4 sites in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The primary objectives of the study are to evaluate the Pharmacokinetics，Safety and tolerability of PEG Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection (FRSW117) in patients with severe hemophilia A. Read more about this study

Who is it for?: Ages 12 to 65 years, men only
Conditions the study is for: Severe Hemophilia A
What is being tested?: ADVATE and FRSW117
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 13 participants
Where: 4 sitesChina
Study dates: 22 Jun 2021to 17 Oct 2021
Phase: Phase 1
Are there results?: None posted in the registry

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 12 to 65 years
Men only
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

Patients with clinically confirmed hemophilia A (coagulation factor VIII <1%) and previous medical records confirming exposure to coagulation factor VIII for ≥150 days (EDs ≥150).
Non-immunodeficient, with some immunity (CD4 > 200/μL).
Platelet count >100×10^9/L.
Normal prothrombin time (PT) or international normalized ratio (INR) <1.3.
Negative lupus anticoagulant.
Fully understand, informed about this study and sign the informed consent form, voluntarily participate in the clinical study and have the ability to complete all study procedures

Who cannot join

Hypersensitivity to the test substance or its excipients (including rodent or hamster protein).
Pre-existing hypersensitivity or allergic reactions to FVIII or IgG2 injection therapy.
Positive FVIII inhibitor at screening (≥0.6 BU/mL), or previous history of FVIII inhibitor Positive history, or family history of inhibitors.
Patients with other coagulation disorders in addition to hemophilia A.
The results of vWF antigen examination lower than normal.
Severe anemia and need blood transfusion (hemoglobin < 60g/L).

Show all 21Show fewer

Patients who have received any standard half-lives FVIII formulations (e.g., Kogenate, Kovaltry, Advate, Xyntha, etc.) or received any other half-life-extending FVIII formulations within 4 days or 5 half-lives (whichever is longer) before administration.
Patients who had used emecizumab within 6 months prior to administration.
Patients with fever, upper respiratory tract infection or allergy symptoms within the previous 2 weeks before screening.
Suffer from other diseases that may increase the risk of bleeding or the risk of thrombosis.
Severe cardiovascular and cerebrovascular diseases: such as cerebral hemorrhage, stroke, myocardial infarction, unstable angina pectoris, congestive heart failure(the current New York Heart Association cardiac function grade III, Hypertension that cannot be controlled with drug treatment: systolic blood pressure> 160 mmHg or diastolic blood pressure> 95 mmHg.
Clinically significant of other systematic diseases: alcoholism, drug abuse, mental disorders and mental retardation.
Significant hepatic or renal impairment (ALT and AST > 2×ULN; serum bilirubin level > 3 × upper limit of normal (ULN)).
Abnormal kidney function: BUN > 2×ULN, Cr > 2.0mg/dL.
One or more clinically significant tests for Hepatitis B Virus Surface Antigen, Human Immunodeficiency Virus (HIV), Antisyphilitic spirulina (TPHA) and Hepatitis C Virus (HCV) Antibody.
Patients who received any anticoagulant or antiplatelet therapy within a week prior screening or need to receive an anticoagulant or antiplatelet therapy during the period of clinical trials.
Systemic immunomodulators (e.g., corticosteroids [equivalent dose of 10 mg/ day prednisone], A-interferon, immunoglobulin, cyclophosphamide, cyclosporine, etc.) were used within 14 days prior to administration or during the study period.
Patients having major surgery or receiving blood or blood components transfusion within 4 weeks prior screening or having planned major surgery schedule during the study.
Patients who previously participated in the other clinical trials within a month prior screening.
Any life-threatening disease or condition which, according to the investigator's judgment, could not benefit from the trial participation.
Patient who is considered by the other investigators not suitable for clinical study.

Trial locations and contacts

4 sites in 1 country.

China4 sites

Nanfang Hospital of Southern Medical University
Guangzhou, Guangzhou, 510515
Jinan central hospital
Jinan, Shandong, 250013
Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College.
Tianjin, Tianjin Municipality, 300020
People's Hospital of Zhengzhou
Zhengzhou, Henan, 450053

Other trials in China

About this study

Official title: An Open-Label, Multicenter Evaluation of the Pharmacokinetics，Safety and Tolerability of PEG Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection (FRSW117) in Patients With Severe Hemophilia A.

The secondary objectives are to monitor anti-durg antibodies and anti-PEG antibodies levels in patients with severe hemophilia A

Conditions: Severe Hemophilia A
Being tested: ADVATE, FRSW117
Keywords: severe Hemophilia A, PEG Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection, Pharmacokinetics, Efficacy and tolerability, Phase I
Medical subject headings: Hemophilia A

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ADVATEDrug
a single dose.
FRSW117Drug
Also called PEG Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection
a single dose.

Study groups in NCT04864743
Study group	Role	What they receive
Arm 1-ADVATE+FRSW117(25 IU/kg)	Experimental	Subjects received two treatments: 25 IU/kg ADVATE in the first period, followed by 25 IU/kg FRSW117 in the second period, with a washout period before each treatment. Receives: Drug: ADVATE; Drug: FRSW117
Arm 2-ADVATE+FRSW117( 50 IU/kg)	Experimental	Subjects received two treatments: 50 IU/kg ADVATE in the first period, followed by 50 IU/kg FRSW117 in the second period, with a washout period before each treatment. Receives: Drug: ADVATE; Drug: FRSW117

What is being measured

The primary outcome is the main question the study is designed to answer.

Cmax from time 0 to the last data point for FRSW117 Measured by One-Stage Clotting Assay.
Maximum plasma activity during a dosing interval for participants.
Measured: Pre-dose to 216 hours after the end of the infusion for Arm1; Pre-dose to 288 hours after the end of the infusion for Arm2
Arm1 - T½ from time 0 to the last data point for FRSW117 Measured by One-Stage Clotting Assay.
Time required for the activity of the drug to reach half of its original value for participants.
Measured: Pre-dose to 216 hours after the end of the infusion for Arm1; Pre-dose to 288 hours after the end of the infusion for Arm2
Arm1 - CL from time 0 to the last data point for FRSW117 Measured by One-Stage Clotting Assay.
Rate at which the body removes the drug, measured as the volume of the plasma cleared of drug per unit time per unit weight for participants.
Measured: Pre-dose to 216 hours after the end of the infusion for Arm1; Pre-dose to 288 hours after the end of the infusion for Arm2
Arm1 - MRT from time 0 to the last data point for FRSW117 Measured by One-Stage Clotting Assay.
The average time that a drug molecule is present in the systemic circulation for participants.
Measured: Pre-dose to 216 hours after the end of the infusion for Arm1; Pre-dose to 288 hours after the end of the infusion for Arm2
Arm1 - Incremental recovery from time 0 to the last data point for FRSW117 Measured by One-Stage Clotting Assay.
The rise in FVIII activity in IU/dL per unit dose administered in IU/kg for participants.
Measured: Pre-dose to 216 hours after the end of the infusion forArm1; Pre-dose to 288 hours after the end of the infusion for Arm2
Arm1 - Cmax from time 0 to the last data point for ADVATE Measured by One-Stage Clotting Assay.
Maximum plasma activity during a dosing interval for participants.
Measured: Pre-dose to 72 hours after the end of the infusion for Arm1; Pre-dose to120 hours after the end of the infusion for Arm2
Arm1 - T½ from time 0 to the last data point for ADVATE Measured by One-Stage Clotting Assay.
Time required for the activity of the drug to reach half of its original value for participants.
Measured: Pre-dose to 72 hours after the end of the infusion for Arm1; Pre-dose to120 hours after the end of the infusion for Arm2
Arm1 - CL from time 0 to the last data point for ADVATE Measured by One-Stage Clotting Assay.
Rate at which the body removes the drug, measured as the volume of the plasma cleared of drug per unit time per unit weight for participants.
Measured: Pre-dose to 72 hours after the end of the infusion for Arm1; Pre-dose to120 hours after the end of the infusion for Arm2
Arm1 - MRT from time 0 to the last data point for ADVATE Measured by One-Stage Clotting Assay.
The average time that a drug molecule is present in the systemic circulation for participants.
Measured: Pre-dose to 72 hours after the end of the infusion for Arm1; Pre-dose to120 hours after the end of the infusion for Arm2
Arm1 - Incremental recovery from time 0 to the last data point for ADVATE Measured by One-Stage Clotting Assay.
The rise in FVIII activity in IU/dL per unit dose administered in IU/kg for participants.
Measured: Pre-dose to 72 hours after the end of the infusion for Arm1; Pre-dose to120 hours after the end of the infusion for Arm2
Number of participants with treatment-emergent adverse events (TEAEs).
Adverse events in the study were classified and evaluated according to the National Cancer Institute's Common Terminology for Adverse Events (NCI CTCAE V5.0).
Measured: assessed up to four weeks after FRSW117 administration.

Secondary outcomes (3)

Evaluation of the level of anti-PEG-rFⅧFc antibody production in participants
Measured: assessed up to four weeks after FRSW117 administration.
Evaluation of the level of anti-PEG antibody production in participants
Measured: assessed up to four weeks after FRSW117 administration.
Number of participants with inhibitor development.
Number of participants who developed a positive FVIII inhibitor level (≥0.6 Bethesda unit [BU]) during the study was summarized and classified as participants developing low titer inhibitor (i.e. ≤ 5.0 BU) and participants developing high titer inhibitor (i.e. > 5.0 BU).
Measured: assessed up to four weeks after FRSW117 administration.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

22 Jun 202117 Oct 2021

First posted29 Apr 2021
Study start22 Jun 2021
Primary completion17 Oct 2021
Study completion17 Oct 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Severe Hemophilia AStudies 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 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 13 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04864743
Sponsor's protocol ID: CTR20210830
Status last verified: May 2023
First submitted: 21 Apr 2021
Last updated: 8 Sep 2023
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 8 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-Label, Multicenter Evaluation of the Pharmacokinetics，Safety and Tolerability of PEG Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection (FRSW117) in Patients With Severe Hemophilia A.
ClinicalTrials.gov ID: NCT04864743
Acronym / sponsor ID: CTR20210830
Conditions: Severe Hemophilia A
Keywords: severe Hemophilia A, PEG Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection, Pharmacokinetics, Efficacy and tolerability, Phase I
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 13 participants (actual)
Lead sponsor: Hangzhou Gensciences Biopharmaceutical Co., Ltd.Industry (pharma, biotech, devices)
Study start: 22 Jun 2021 (actual)
Primary completion: 17 Oct 2021 (actual)
Study completion: 17 Oct 2021 (actual)
First posted: 29 Apr 2021 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The secondary objectives are to monitor anti-durg antibodies and anti-PEG antibodies levels in patients with severe hemophilia A

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Arm 1-ADVATE+FRSW117(25 IU/kg)	Experimental	Drug: ADVATE, Drug: FRSW117Subjects received two treatments: 25 IU/kg ADVATE in the first period, followed by 25 IU/kg FRSW117 in the second period, with a washout period before each treatment.
Arm 2-ADVATE+FRSW117( 50 IU/kg)	Experimental	Drug: ADVATE, Drug: FRSW117Subjects received two treatments: 50 IU/kg ADVATE in the first period, followed by 50 IU/kg FRSW117 in the second period, with a washout period before each treatment.

Who may qualify

Ages: 12 to 65 years
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (6 listed)

Patients with clinically confirmed hemophilia A (coagulation factor VIII <1%) and previous medical records confirming exposure to coagulation factor VIII for ≥150 days (EDs ≥150).
Non-immunodeficient, with some immunity (CD4 > 200/μL).
Platelet count >100×10^9/L.
Normal prothrombin time (PT) or international normalized ratio (INR) <1.3.
Negative lupus anticoagulant.

Key exclusion criteria (21 listed)

Hypersensitivity to the test substance or its excipients (including rodent or hamster protein).
Pre-existing hypersensitivity or allergic reactions to FVIII or IgG2 injection therapy.
Positive FVIII inhibitor at screening (≥0.6 BU/mL), or previous history of FVIII inhibitor Positive history, or family history of inhibitors.
Patients with other coagulation disorders in addition to hemophilia A.
The results of vWF antigen examination lower than normal.

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
ADVATEa single dose.	Drug	Arm 1-ADVATE+FRSW117(25 IU/kg), Arm 2-ADVATE+FRSW117( 50 IU/kg)
FRSW117Also: PEG Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injectiona single dose.	Drug	Arm 1-ADVATE+FRSW117(25 IU/kg), Arm 2-ADVATE+FRSW117( 50 IU/kg)

Primary outcome

Cmax from time 0 to the last data point for FRSW117 Measured by One-Stage Clotting Assay.
Time frame: Pre-dose to 216 hours after the end of the infusion for Arm1; Pre-dose to 288 hours after the end of the infusion for Arm2
Maximum plasma activity during a dosing interval for participants.
Arm1 - T½ from time 0 to the last data point for FRSW117 Measured by One-Stage Clotting Assay.
Time frame: Pre-dose to 216 hours after the end of the infusion for Arm1; Pre-dose to 288 hours after the end of the infusion for Arm2
Time required for the activity of the drug to reach half of its original value for participants.
Arm1 - CL from time 0 to the last data point for FRSW117 Measured by One-Stage Clotting Assay.
Time frame: Pre-dose to 216 hours after the end of the infusion for Arm1; Pre-dose to 288 hours after the end of the infusion for Arm2
Rate at which the body removes the drug, measured as the volume of the plasma cleared of drug per unit time per unit weight for participants.
Arm1 - MRT from time 0 to the last data point for FRSW117 Measured by One-Stage Clotting Assay.
Time frame: Pre-dose to 216 hours after the end of the infusion for Arm1; Pre-dose to 288 hours after the end of the infusion for Arm2
The average time that a drug molecule is present in the systemic circulation for participants.
Arm1 - Incremental recovery from time 0 to the last data point for FRSW117 Measured by One-Stage Clotting Assay.
Time frame: Pre-dose to 216 hours after the end of the infusion forArm1; Pre-dose to 288 hours after the end of the infusion for Arm2
The rise in FVIII activity in IU/dL per unit dose administered in IU/kg for participants.
Arm1 - Cmax from time 0 to the last data point for ADVATE Measured by One-Stage Clotting Assay.
Time frame: Pre-dose to 72 hours after the end of the infusion for Arm1; Pre-dose to120 hours after the end of the infusion for Arm2
Maximum plasma activity during a dosing interval for participants.
Arm1 - T½ from time 0 to the last data point for ADVATE Measured by One-Stage Clotting Assay.
Time frame: Pre-dose to 72 hours after the end of the infusion for Arm1; Pre-dose to120 hours after the end of the infusion for Arm2
Time required for the activity of the drug to reach half of its original value for participants.
Arm1 - CL from time 0 to the last data point for ADVATE Measured by One-Stage Clotting Assay.
Time frame: Pre-dose to 72 hours after the end of the infusion for Arm1; Pre-dose to120 hours after the end of the infusion for Arm2
Rate at which the body removes the drug, measured as the volume of the plasma cleared of drug per unit time per unit weight for participants.
Arm1 - MRT from time 0 to the last data point for ADVATE Measured by One-Stage Clotting Assay.
Time frame: Pre-dose to 72 hours after the end of the infusion for Arm1; Pre-dose to120 hours after the end of the infusion for Arm2
The average time that a drug molecule is present in the systemic circulation for participants.
Arm1 - Incremental recovery from time 0 to the last data point for ADVATE Measured by One-Stage Clotting Assay.
Time frame: Pre-dose to 72 hours after the end of the infusion for Arm1; Pre-dose to120 hours after the end of the infusion for Arm2
The rise in FVIII activity in IU/dL per unit dose administered in IU/kg for participants.
Number of participants with treatment-emergent adverse events (TEAEs).
Time frame: assessed up to four weeks after FRSW117 administration.
Adverse events in the study were classified and evaluated according to the National Cancer Institute's Common Terminology for Adverse Events (NCI CTCAE V5.0).

3 secondary outcomes

Evaluation of the level of anti-PEG-rFⅧFc antibody production in participants
Time frame: assessed up to four weeks after FRSW117 administration.
Evaluation of the level of anti-PEG antibody production in participants
Time frame: assessed up to four weeks after FRSW117 administration.
Number of participants with inhibitor development.
Time frame: assessed up to four weeks after FRSW117 administration.

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2023.
Individual participant dataSharing planned: No

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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.

Renchi Yang, PhD principal investigator

Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College.

4 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ADVATE and FRSW117 in people with Severe Hemophilia A, run by Hangzhou Gensciences Biopharmaceutical Co., Ltd. at 4 sites in China.

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 6 inclusion and 21 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 8 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in China. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Cmax from time 0 to the last data point for FRSW117 Measured by One-Stage Clotting Assay. (time frame: Pre-dose to 216 hours after the end of the infusion for Arm1; Pre-dose to 288 hours after the end of the infusion for Arm2). The study lists 11 primary outcomes in all. 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 NCT04864743.

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 8 Sep 2023.