An interventional study of Intra-articular Bevacizumab in Hemophilia and Chronic Synovitis, sponsored by Khyber Medical University Peshawar. Completed at 2 sites in Pakistan. Per ClinicalTrials.gov, last updated 2026-06-25.
Sponsored by Khyber Medical University Peshawar · Not applicable, Interventional, and Treatment
Hemophilia is an inherited bleeding disorder characterized by deficiency of clotting factors, leading to increased bleeding tendencies. The most common complications are joint bleeds (hemarthroses), which cause chronic changes in joints and ultimately disability. Recurrent hemarthroses often result from chronic synovitis in target joints of patients with hemophilia, a process driven by Vascular Endothelial Growth Factor (VEGF) mediated pathological angiogenesis. Intra-articular administration of Bevacizumab, a VEGF neutralizing monoclonal antibody, may block this process and reduce the frequency of recurrent joint bleeds. This study evaluates the efficacy and safety of intra-articular Bevacizumab for preventing recurrent hemarthrosis in patients with hemophilia and chronic synovitis.
Hemophilia A is the most prevalent inherited bleeding disorder in Pakistan, accounting for approximately 69% of all hemophilia cases. A major complication is recurrent joint bleeding (hemarthrosis), which leads to chronic synovitis and progressive hemophilic arthropathy. This joint deterioration significantly impairs mobility and quality of life.
The underlying pathophysiology is driven by repeated hemarthroses, which cause increased local expression of Vascular Endothelial Growth Factor (VEGF). VEGF promotes abnormal angiogenesis and synovial proliferation, perpetuating a cycle of inflammation and bleeding, even when symptoms are not overt.
Bevacizumab is a recombinant humanized monoclonal antibody that specifically inhibits VEGF. Local intra-articular administration offers a targeted therapeutic approach to disrupt this pathogenic cycle directly at the site of pathology. By neutralizing VEGF, Bevacizumab may mitigate synovitis, reduce bleeding frequency, and slow progression of hemophilic arthropathy, while minimizing systemic exposure and associated adverse effects.
To investigate this therapeutic strategy, a two-year, open-label, single-arm clinical trial will be conducted at the Institute of Pathology and Diagnostic Medicine (IPDM), Khyber Medical University (KMU), and Hayatabad Medical Complex, Peshawar, Pakistan. A total of 25 participants with Hemophilia A and chronic synovitis in one or more target joints (knee, elbow, or ankle) will be enrolled.
All participants will receive intra-articular Bevacizumab injections following prophylactic factor replacement therapy to prevent procedure-related bleeding. The first four participants will receive 20 mg/0.8 mL per injection. If well tolerated without major toxicities, the remaining participants will receive 40 mg/1.6 mL per injection. Each injection will be administered into the target joint once every 28 days for a total of four doses.
The primary efficacy outcome will be the change in the Annualized Bleeding Rate (ABR) of the target joint, calculated from 3-month pre- and post-treatment data. Secondary outcomes will include changes in joint health assessed using the Hemophilia Joint Health Score (HJHS, Version 2.1; range 0-124, where higher scores indicate worse joint health) and synovial inflammation measured by Magnetic Resonance Imaging (MRI) with the International Prophylaxis Study Group (IPSG)-compatible scoring system.
This study may provide critical insight into a novel, VEGF-targeted strategy for managing chronic synovitis in hemophilia patients and preserving long-term joint health.
844 studies on the registry are indexed under Hemophilia A; 138 are open to participants now.
This study's enrollment of 18 is below the median of 30 across 499 interventional studies indexed under Hemophilia A.
Browse Hemophilia A studies →Khyber Medical University Peshawar is the lead sponsor of 54 studies on the registry; 13 are open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
All participants will receive intra-articular injections of Bevacizumab. The initial dose for the first four patients will be 20 mg/0.8 ml. If no major toxicities are observed, the dose will be escalated to 40 mg/1.6 ml for the remaining patients. Injections will be administered monthly for a duration of 4 months.
Drug: Intra-articular Bevacizumab
This clinical trial investigates the intra-articular injection of Bevacizumab, a recombinant humanized monoclonal antibody that inhibits Vascular Endothelial Growth Factor (VEGF). The intervention functions by binding to and neutralizing VEGF-A, thereby blocking the pathogenic angiogenesis and vascular permeability that characterizes chronic hemophilic synovitis. For administration, the first four patients will receive a dose of 20 mg in 0.8 mL per injection, and if this is well-tolerated without major toxicities, the dose for all subsequent patients will be increased to 40 mg in 1.6 mL. Each injection will be administered directly into the target joint (knee, elbow, or ankle) once every 28 days for a total of four doses. Crucially, all injections will be performed only after appropriate prophylactic factor replacement to mitigate any procedure-related bleeding risk.
Also known as: Avastin, Genentech
Annualized Bleeding Rate (ABR) of the Target Joint
The efficacy of the intervention will be assessed by the change in the number of recurrent hemarthrosis episodes specifically in the treated target joint. The rate will be annualized from data collected over a 3-month period. Response will be categorized as: 'Excellent' (0 bleeds), 'Good' (75-99% reduction), 'Fair' (50-74% reduction), or 'Poor' (\<50% reduction).
Time frame: Baseline (3 months pre-treatment) compared to the 3-month period following the completion of the treatment protocol (i.e., 3 months after the 4th injection).
Clinical Joint Health Score
Change in joint health and function as measured by the Hemophilia Joint Health Score (HJHS 2.1), a standardized physical examination tool that assesses pain, swelling, muscle atrophy, crepitus on motion, range of motion (flexion/extension loss), strength, and gait. Scale Range: 0 to 124 (higher scores indicate worse joint health and function). Interpretation: 0 = best outcome (no joint damage or impairment) 124 = worst outcome (severe joint involvement and functional limitation)
Time frame: Baseline scores compared to scores at 1, 3, 6, and 12 months after initiation of therapy
Synovial Hypertrophy
Change in synovial membrane thickness in the target joint as assessed by MRI, scored according to the IPSG MRI scale for synovial hypertrophy (0-3; 0 = none, 3 = \>5 mm).
Time frame: Baseline MRI (before starting therapy) compared to MRI performed 6 months after completion of therapy.
Joint Effusion/Hemarthrosis
Change in effusion or hemarthrosis volume in the target joint, assessed using the IPSG MRI scale (0-3; 0 = none, 3 = severe joint distention).
Time frame: Baseline vs. 6 months after completion of therapy.
Synovial Inflammation Composite (Soft Tissue Subtotal)
Change in the combined soft tissue inflammation score, calculated as the sum of effusion/hemarthrosis, synovial hypertrophy, and hemosiderin deposition (range 0-9)..
Time frame: Baseline vs. 6 months after completion of therapy.
Plan to share: Yes — Individual participant data that underlie the results reported in the primary publication (after de-identification) will be made available beginning 9 months following article publication and will remain available for a period of at least 36 months.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report
Time frame: De-identified individual participant data will be made available 9 months after the publication of the primary results and will remain accessible for at least 36 months. Extensions may be considered upon request.
Access criteria: Access will be granted to researchers who provide a methodologically sound proposal for use in achieving the goals of the approved proposal. Requestors will be required to submit a proposal to the corresponding author and sign a Data Access Agreement to ensure appropriate use of the data.
Ran from Sep 2025 to primary completion in Mar 2026, 6 months.
Of 72 non-industry interventional studies with no phase under Hemophilia A, half reached primary completion within 11 months of starting (the median), counting those still running; a quarter within 5 and three quarters within 38. This study's 6 months is below that.
Counting every sponsor, half of 75 studies reached it within 11 months; a quarter within 5 and three quarters within 38.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Jun 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Bevacizumab
Khyber Medical University Peshawar