Intra-Articular Bevacizumab for Preventing Recurrent Hemarthrosis in Hemophilia With Chronic Synovitis

NCT07187661 | Completed DMC

• 1 other identifier: KMU/DIR/CTU/2025/006
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Hemophilia; Chronic Synovitis

Keywords

Hemophilia A; Chronic Synovitis; Hemarthrosis; Hemophilic Arthropathy

Outcome Measures

Primary Outcomes (5)

• 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).

  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)

  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).

  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).

  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)..

  Baseline vs. 6 months after completion of therapy.

Study Arms (1)

Intra-articular Bevacizumab

EXPERIMENTAL

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

Interventions

Intra-articular Bevacizumab DRUG

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

Intra-articular Bevacizumab

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed diagnosis of Hemophilia A.
• Presence of one or more target joints (knee, elbow, ankle) with chronic synovitis and a history of \>2 hemarthrosis episodes in the past 6 months.
• Target joint World Federation of Hemophilia (WFH) joint score of 2-3.
• Adequate hematological, renal, and liver function (as specified by protocol lab values).
• Ability and willingness to provide informed consent and comply with the study protocol.

You may not qualify if:

• HIV positive diagnosis.
• Severely damaged joints or anatomical limitations preventing safe injection.
• Contraindications to MRI.
• Uncontrolled hypertension.
• Recent major surgery/trauma (\<28 days).
• Serious non-healing wound, active cardiovascular disease, or other significant comorbidities that could increase risk or interfere with the study.

Sponsors & Collaborators

• Khyber Medical University Peshawar: lead

Study Sites (2)

Hayatabad Medical Complex

Peshawar, KPK, 25000, Pakistan

Location

Institute of Pathology and Diagnostic Medicine (IPDM)

Peshawar, KPK, 25000, Pakistan

Location

Related Publications (5)

• Sadiq MA, Ahmed S, Afzal M, Tasfeen S. A basis for prenatal diagnosis of Haemophilia-A in Pakistani patients. Pak J Med Sci. 2022 Nov-Dec;38(8):2065-2070. doi: 10.12669/pjms.38.8.6524.

  PMID: 36415265 BACKGROUND

• Hirayama AB, Silva AKCD, Rocha JS, Roberti MDRF. Prevalence of symptoms in hemophilia carriers in comparison with the general population: a systematic review. Hematol Transfus Cell Ther. 2019 Oct-Dec;41(4):349-355. doi: 10.1016/j.htct.2019.02.006. Epub 2019 Jun 17.

  PMID: 31412987 BACKGROUND

• Gualtierotti R, Solimeno LP, Peyvandi F. Hemophilic arthropathy: Current knowledge and future perspectives. J Thromb Haemost. 2021 Sep;19(9):2112-2121. doi: 10.1111/jth.15444. Epub 2021 Jul 27.

  PMID: 34197690 BACKGROUND

• Hassan S, Monahan RC, Mauser-Bunschoten EP, van Vulpen LFD, Eikenboom J, Beckers EAM, Hooimeijer L, Ypma PF, Nieuwenhuizen L, Coppens M, Schols SEM, Leebeek FWG, Smit C, Driessens MH, le Cessie S, van Balen EC, Rosendaal FR, van der Bom JG, Gouw SC. Mortality, life expectancy, and causes of death of persons with hemophilia in the Netherlands 2001-2018. J Thromb Haemost. 2021 Mar;19(3):645-653. doi: 10.1111/jth.15182. Epub 2020 Dec 18.

  PMID: 33217158 BACKGROUND

• Iorio A, Stonebraker JS, Chambost H, Makris M, Coffin D, Herr C, Germini F; Data and Demographics Committee of the World Federation of Hemophilia. Establishing the Prevalence and Prevalence at Birth of Hemophilia in Males: A Meta-analytic Approach Using National Registries. Ann Intern Med. 2019 Oct 15;171(8):540-546. doi: 10.7326/M19-1208. Epub 2019 Sep 10.

  PMID: 31499529 BACKGROUND

MeSH Terms

Conditions

Hemophilia A; Hemarthrosis

Interventions

Bevacizumab; (18F)GTP1

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; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Dr Kinza Ayaz, MBBS

  Khyber Medical University Peshawar

  PRINCIPAL INVESTIGATOR

• Prof. Dr. Yasar M Yousafzai, PhD

  Khyber Medical University Peshawar

  PRINCIPAL INVESTIGATOR

• Dr. Muhammad Tariq Masood Khan, MBBS

  Khyber Medical University Peshawar

  PRINCIPAL INVESTIGATOR

• Dr Khalid Khan, MBBS

  Khyber Medical University Peshawar

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: This is an open-label study. No masking is used.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is an interventional clinical trial utilizing a pre- and post-study design. It is a single-arm study, meaning all enrolled participants will receive the investigational intervention. The trial is open-label, with no masking (blinding) of participants, care providers, investigators, or outcomes assessors. As it is a single-arm study, there is no allocation or randomization process. The total enrollment for this study is 25 participants.

Study Record Dates

• First Submitted: September 10, 2025
• First Posted: September 23, 2025
• Study Start: September 9, 2025
• Primary Completion: March 28, 2026
• Study Completion: April 15, 2026
• Last Updated: June 25, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.

Locations

PA (2)