Intra-articular Bevacizumab for Recurrent Hemarthroses at Target Joints With Chronic Hemophilic Synovitis

NCT02060305 | Terminated Phase 1 DMC

• 1 other identifier: 201305041MINB
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Hemophilia; Synovitis

Outcome Measures

Primary Outcomes (1)

• 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

  one year

Secondary Outcomes (4)

• The dynamics of serum and synovial fluid VEGF concentrations

  one year

• The vasculature changes by MR image study

  one year

• The pain score during the intra-articular injection procedure

  6 months

• The frequency and severity of adverse effects during the study period

  one year

Study Arms (1)

Bevacizumab

EXPERIMENTAL

Bevacizumab intra-articular injection; dose 20mg\~40mg every 28 days for 4 times

Drug: Bevacizumab intra-articular injection

Interventions

Bevacizumab intra-articular injection DRUG

Bevacizumab, 20\~40mg, intra-articular injection every 28 days for 4 times

Also known as: Bevacizumab (Avastin) intra-articular injection

Bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (1)

Hematology Division, National Taiwan University Hospital

Taipei, 100, Taiwan

Location

MeSH Terms

Conditions

Hemophilia A; Synovitis

Interventions

Bevacizumab; Injections, Intra-Articular

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Joint Diseases; Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Injections; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Shang-Ju Wu, MD

  National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: National Taiwan University Hospital

Model Details: Open-label

Study Record Dates

• First Submitted: February 5, 2014
• First Posted: February 12, 2014
• Study Start: February 1, 2014
• Primary Completion: June 30, 2020
• Study Completion: June 30, 2020
• Last Updated: July 6, 2021

Record last verified: 2021-07

Locations

TW (1)