HemophiliaPhase 1NCT02060305
Intra-articular Bevacizumab for Recurrent Hemarthroses at Target Joints With Chronic Hemophilic Synovitis
A Phase 1 study testing Bevacizumab intra-articular injection in people with Hemophilia and Synovitis, run by National Taiwan University Hospital at 1 site in Taiwan.
Trial summary
Primary Objective The efficacy of intra-articular bevacizumab injection for secondary prevention of recurrent hemarthroses for hemophilia patients who has had target joints with chronic synovitis. The safety profiles of intra-articular bevacizumab injection for hemophilia patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hemophilia, Synovitis
- What is being tested?
- Bevacizumab intra-articular injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteTaiwan
- Study dates
- 1 Feb 2014to 30 Jun 2020
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 years or older, with a diagnosis of hemophilia A or B.
- Subjects with target one or more target joints of chronic synovitis with recurrent hemarthroses more than 2 times in recent 6 months. The target joint(s) are limited to knee, elbow, or ankle, with substantial severity (World Federation of Hemophilia Score =2~3)
- White cell count ≧ 3000/μL, Hemoglobin level ≧ 10 g/dL, and platelets ≧ 100,000/μL
- Serum creatinine ≦1.5 X the upper limit of normal (ULN)
- Total bilirubin ≦1.5 X ULN; aspartate and alanine aminotransferase (AST, ALT) ≦2.0 x ULN.
- Willingness and ability to comply with the study scheduled visits, treatment plans, laboratory tests, and other procedures, including the completion of patient questionnaires.
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- Women of childbearing potential must have a negative serum pregnancy test done 1 week prior to the administration of the study drug. She and her partner should prevent pregnancy (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) up to at least 6 months after last treatment completion or the last drug dose, whatever happens first.
- Eastern Cooperative Oncology Group (ECOG) performance status: 0~2
- Signed written informed consent according to ICH/GCP and the local regulations (approved by the Institutional Review Board [IRB]/Independent Ethics Committee [IEC]) will be obtained prior to any study specific screening procedures.
Who cannot join
- Subjects with known HIV infection.
- Subjects whose target joints have been heavily damaged into deformity or arthropathy, or whose target joints cannot receive intra-articular injection.
- Subjects who cannot receive MRI study.
- Subjects with uncontrolled hypertension (systolic blood pressure > 160 mm Hg, diastolic blood pressure > 90 mm Hg).
- Subjects who experienced major surgical procedures, open biopsy or significant traumatic injury within 28 days prior to the first dose of Bevacizumab administration (Patients must have recovered from any major surgery), or who have anticipation of need for major surgical procedures during the course of the study.
- Subjects with serious non-healing wound or ulcer.
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- Subjects with clinically significant (i.e. active) cardiovascular disease. For example, cerebrovascular accidents or stroke in the preceding six months, myocardial infarction or unstable angina in the preceding six months, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication.
- Pregnancy (positive serum pregnancy test) and lactation
- Subjects who have other impaired major organ dysfunction, active infection, abnormal laboratory or physical findings, or co-morbidities that, in the investigators' adjustment, may substantially increase the risk associated with the patients' participation in the study.
Trial locations and contacts
1 site in 1 country.
Taiwan1 site
Hematology Division, National Taiwan University Hospital
Taipei, 100
About this study
Official title: A Pilot Study About the Safety and Efficacy of Intra-articular Bevacizumab (Avastin) for Recurrent Hemarthroses at Target Joints With Chronic Hemophilic Synovitis
Primary Objective The efficacy of intra-articular bevacizumab injection for secondary prevention of recurrent hemarthroses for hemophilia patients who has had target joints with chronic synovitis. The safety profiles of intra-articular bevacizumab injection for hemophilia patients.
Study Population Adult hemophilia patients who have had one or more target joints with chronic synovitis and recurrent hemarthroses.
Read more
Investigational therapy: Intra-articular injection of Bevacizumab (20 or 40 mg/ 0.8 or 1.6 ml/ dose) every month (28 days) for up to 4 months, depending on the improvement of target joint bleeding.
Study Design The estimated study period is between Jan 2014 and Dec 2015. Totally 10 joints will be enrolled for this pilot study. Before enrollment, the joint(s) will be evaluated for their severity both clinically (by 10-point Pain Score, range of motion for the target joint, and World Federation of Hemophilia Score) and by MRI (using the compatible MRI scales developed by International Prophylaxis Study Group [IPSG]). Intra-articular injection of bevacizumab will be administered, after prophylactic factor supplementation, every month for up to four injections. In the first four patients, 20mg of bevacizumab will be administered. If there are no Gr 3 or Gr4 dose-limiting toxicities, bevacizumab dose will be escalated to 40mg in the other 6 patients. Before every procedure, the plasma and the synovial fluid samples will be collected for VEGF quantification for the correlative biomarker study. After completing the protocol treatment, the efficacy parameters as well as the safety profiles will be evaluated.
Read the detailed description
Hypothesis: The mechanism of recurrent hemarthroses (joint bleeds) resulted from chronic synovitis of target joints in hemophilic patients is thought to be a VEGF-based neo-angiogenic process. Local anti-VEGF therapy with intra-articular bevacizumab (Avastin), a VEGF-neutralizing monoclonal antibody that can efficiently antagonize VEGF activity, may block the process and decrease the frequency of recurrent bleeding episodes. In addition, we proved that intra-articular injection of bevacizumab in rat model is safe without significant local or systemic adverse events.
Primary Objective The efficacy of intra-articular bevacizumab injection for secondary prevention of recurrent hemarthroses for hemophilia patients who has had target joints with chronic synovitis. The safety profiles of intra-articular bevacizumab injection for hemophilia patients.
Study Population Adult hemophilia patients who have had one or more target joints with chronic synovitis and recurrent hemarthroses.
Investigational therapy: Intra-articular injection of Bevacizumab (20 or 40 mg/ 0.8 or 1.6 ml/ dose) every month (28 days) for up to 4 months, depending on the improvement of target joint bleeding.
Study Design The estimated study period is between Jan 2014 and Dec 2015. Totally 10 joints will be enrolled for this pilot study. Before enrollment, the joint(s) will be evaluated for their severity both clinically (by 10-point Pain Score, range of motion for the target joint, and World Federation of Hemophilia Score) and by MRI (using the compatible MRI scales developed by International Prophylaxis Study Group [IPSG]). Intra-articular injection of bevacizumab will be administered, after prophylactic factor supplementation, every month for up to four injections. In the first four patients, 20mg of bevacizumab will be administered. If there are no Gr 3 or Gr4 dose-limiting toxicities, bevacizumab dose will be escalated to 40mg in the other 6 patients. Before every procedure, the plasma and the synovial fluid samples will be collected for VEGF quantification for the correlative biomarker study. After completing the protocol treatment, the efficacy parameters as well as the safety profiles will be evaluated.
Assessments The efficacy: the differences of total episodes of recurrent hemarthroses within 3 months before and after completing bevacizumab intra-articular injection. Post-procedure target joints bleedings will be recorded at intervals of 1st, 3rd, 6th, and 12th months. The total absence of haemarthrosis (zero bleeding) is rated as "excellent" response; bleeding reduction between 75% and 99% is rated "good", between 50% and 74% as "fair", and below 50% as "poor".
- Conditions
- Hemophilia, Synovitis
- Being tested
- Bevacizumab intra-articular injection
- Medical subject headings
- Hemophilia A, Synovitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bevacizumab intra-articular injectionDrug
Also called Bevacizumab (Avastin) intra-articular injection
Bevacizumab, 20~40mg, intra-articular injection every 28 days for 4 times
| Study group | Role | What they receive |
|---|---|---|
| Bevacizumab | Experimental | Bevacizumab intra-articular injection; dose 20mg~40mg every 28 days for 4 times Receives: Drug: Bevacizumab intra-articular injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recurrent hemarthroses rate
The efficacy of intra-articular bevacizumab injection for secondary prevention of recurrent hemarthroses for hemophilia patients who has had target joints with chronic synovitis. The efficacy will be measure by the recurrent hemarthroses rate after the investigational therapy
Measured: one year
Secondary outcomes (4)
The dynamics of serum and synovial fluid VEGF concentrations
Measured: one year
The vasculature changes by MR image study
Measured: one year
The pain score during the intra-articular injection procedure
Measured: 6 months
The frequency and severity of adverse effects during the study period
The adverse effects, both systemic (Ex. hypertension, proteinuria, or bleeding episodes), and localized (Ex. joint internal bleeding or local symptoms), will be monitored and recorded during the investigation period.
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2014 (estimated)
- Study start1 Feb 2014
- Primary completion30 Jun 2020
- Study completion30 Jun 2020
Why it stopped: Very slow enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HemophiliaStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Model description
- Open-label
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Statistical Center, NTUHCTC, National Taiwan University Hospital
- Investigators
- Shang-Ju Wu, MD, Principal investigator, National Taiwan University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02060305
- Sponsor's protocol ID
- 201305041MINB
- Status last verified
- Jul 2021
- First submitted
- 5 Feb 2014
- Last updated
- 6 Jul 2021
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study About the Safety and Efficacy of Intra-articular Bevacizumab (Avastin) for Recurrent Hemarthroses at Target Joints With Chronic Hemophilic Synovitis
- ClinicalTrials.gov ID
- NCT02060305
- Acronym / sponsor ID
- 201305041MINB
- Conditions
- Hemophilia, Synovitis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Very slow enrollment
- Enrolment
- 5 participants (actual)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- 1 Feb 2014
- Primary completion
- 30 Jun 2020 (actual)
- Study completion
- 30 Jun 2020 (actual)
- First posted
- 12 Feb 2014 (estimated)
- 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.
Primary Objective The efficacy of intra-articular bevacizumab injection for secondary prevention of recurrent hemarthroses for hemophilia patients who has had target joints with chronic synovitis. The safety profiles of intra-articular bevacizumab injection for hemophilia patients.
Study Population Adult hemophilia patients who have had one or more target joints with chronic synovitis and recurrent hemarthroses.
Investigational therapy: Intra-articular injection of Bevacizumab (20 or 40 mg/ 0.8 or 1.6 ml/ dose) every month (28 days) for up to 4 months, depending on the improvement of target joint bleeding.
Study Design The estimated study period is between Jan 2014 and Dec 2015. Totally 10 joints will be enrolled for this pilot study. Before enrollment, the joint(s) will be evaluated for their severity both clinically (by 10-point Pain Score, range of motion for the target joint, and World Federation of Hemophilia Score) and by MRI (using the compatible MRI scales developed by International Prophylaxis Study Group [IPSG]). Intra-articular injection of bevacizumab will be administered, after prophylactic factor supplementation, every month for up to four injections. In the first four patients, 20mg of bevacizumab will be administered. If there are no Gr 3 or Gr4 dose-limiting toxicities, bevacizumab dose will be escalated to 40mg in the other 6 patients. Before every procedure, the plasma and the synovial fluid samples will be collected for VEGF quantification for the correlative biomarker study. After completing the protocol treatment, the efficacy parameters as well as the safety profiles will be evaluated.
Detailed description
Hypothesis: The mechanism of recurrent hemarthroses (joint bleeds) resulted from chronic synovitis of target joints in hemophilic patients is thought to be a VEGF-based neo-angiogenic process. Local anti-VEGF therapy with intra-articular bevacizumab (Avastin), a VEGF-neutralizing monoclonal antibody that can efficiently antagonize VEGF activity, may block the process and decrease the frequency of recurrent bleeding episodes. In addition, we proved that intra-articular injection of bevacizumab in rat model is safe without significant local or systemic adverse events.
Primary Objective The efficacy of intra-articular bevacizumab injection for secondary prevention of recurrent hemarthroses for hemophilia patients who has had target joints with chronic synovitis. The safety profiles of intra-articular bevacizumab injection for hemophilia patients.
Study Population Adult hemophilia patients who have had one or more target joints with chronic synovitis and recurrent hemarthroses.
Investigational therapy: Intra-articular injection of Bevacizumab (20 or 40 mg/ 0.8 or 1.6 ml/ dose) every month (28 days) for up to 4 months, depending on the improvement of target joint bleeding.
Study Design The estimated study period is between Jan 2014 and Dec 2015. Totally 10 joints will be enrolled for this pilot study. Before enrollment, the joint(s) will be evaluated for their severity both clinically (by 10-point Pain Score, range of motion for the target joint, and World Federation of Hemophilia Score) and by MRI (using the compatible MRI scales developed by International Prophylaxis Study Group [IPSG]). Intra-articular injection of bevacizumab will be administered, after prophylactic factor supplementation, every month for up to four injections. In the first four patients, 20mg of bevacizumab will be administered. If there are no Gr 3 or Gr4 dose-limiting toxicities, bevacizumab dose will be escalated to 40mg in the other 6 patients. Before every procedure, the plasma and the synovial fluid samples will be collected for VEGF quantification for the correlative biomarker study. After completing the protocol treatment, the efficacy parameters as well as the safety profiles will be evaluated.
Assessments The efficacy: the differences of total episodes of recurrent hemarthroses within 3 months before and after completing bevacizumab intra-articular injection. Post-procedure target joints bleedings will be recorded at intervals of 1st, 3rd, 6th, and 12th months. The total absence of haemarthrosis (zero bleeding) is rated as "excellent" response; bleeding reduction between 75% and 99% is rated "good", between 50% and 74% as "fair", and below 50% as "poor".
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open-label
| Arm | Type | Receives |
|---|---|---|
| Bevacizumab | Experimental | Drug: Bevacizumab intra-articular injectionBevacizumab intra-articular injection; dose 20mg~40mg every 28 days for 4 times |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age 18 years or older, with a diagnosis of hemophilia A or B.
- Subjects with target one or more target joints of chronic synovitis with recurrent hemarthroses more than 2 times in recent 6 months. The target joint(s) are limited to knee, elbow, or ankle, with substantial severity (World Federation of Hemophilia Score =2~3)
- White cell count ≧ 3000/μL, Hemoglobin level ≧ 10 g/dL, and platelets ≧ 100,000/μL
- Serum creatinine ≦1.5 X the upper limit of normal (ULN)
- Total bilirubin ≦1.5 X ULN; aspartate and alanine aminotransferase (AST, ALT) ≦2.0 x ULN.
Key exclusion criteria (9 listed)
- Subjects with known HIV infection.
- Subjects whose target joints have been heavily damaged into deformity or arthropathy, or whose target joints cannot receive intra-articular injection.
- Subjects who cannot receive MRI study.
- Subjects with uncontrolled hypertension (systolic blood pressure > 160 mm Hg, diastolic blood pressure > 90 mm Hg).
- Subjects who experienced major surgical procedures, open biopsy or significant traumatic injury within 28 days prior to the first dose of Bevacizumab administration (Patients must have recovered from any major surgery), or who have anticipation of need for major surgical procedures during the course of the study.
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 |
|---|---|---|
| Bevacizumab intra-articular injectionAlso: Bevacizumab (Avastin) intra-articular injectionBevacizumab, 20~40mg, intra-articular injection every 28 days for 4 times | Drug | Bevacizumab |
Primary outcome
Recurrent hemarthroses rate
Time frame: one year
The efficacy of intra-articular bevacizumab injection for secondary prevention of recurrent hemarthroses for hemophilia patients who has had target joints with chronic synovitis. The efficacy will be measure by the recurrent hemarthroses rate after the investigational therapy
4 secondary outcomes
The dynamics of serum and synovial fluid VEGF concentrations
Time frame: one year
The vasculature changes by MR image study
Time frame: one year
The pain score during the intra-articular injection procedure
Time frame: 6 months
The frequency and severity of adverse effects during the study period
Time frame: one year
Results and safety
The study was stopped early (reason given: Very slow enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 2021.
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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.
Shang-Ju Wu, MD principal investigator
National Taiwan University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Bevacizumab intra-articular injection in people with Hemophilia and Synovitis, run by National Taiwan University Hospital at 1 site in Taiwan.
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 9 inclusion and 9 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: stopped early, as of the sponsor's last update on 6 Jul 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 Taiwan. 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 was stopped early (reason given: Very slow enrollment). Results are not available in the source record.
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?
Recurrent hemarthroses rate (time frame: one year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 Jul 2021.