Inflammation

MIMEDX and IAG Partner to Support Knee Osteoarthritis Ph 3 Clinical Trial Program

MIMEDX and IAG Partner to Support Knee Osteoarthritis Ph 3 Clinical Trial Program

Image Analysis Group to Partner with MIMEDX in Support of MIMEDX’s Knee Osteoarthritis Clinical Trial Program

Image Analysis Group to Provide Imaging Strategy and Advanced Imaging Analytics in Support of MIMEDX’s Knee Osteoarthritis Clinical Trial Program

MIMEDX is a transformational placental biologics company, developing and distributing placental tissue allografts and IAG, Image Analysis Group, a strategic bio-pharma imaging expert announce a partnership in the development of MIMEDX’s mdHACM.

The IAG team has significant experience in using medical imaging to support drug development.

‘We have significant evidence that mdHACM injected into the knees of people with OA provides lasting pain relief and improves function, and we believe it has potential as a DMOAD. MIMEDX has discovered how to preserve the remarkable healing properties of placental membranes when we produce mdHACM, and we have demonstrated that it contains many proteins that influence the biology of cartilage-forming cells and reduce inflammation. We believe these active proteins contribute to the striking, long-lasting benefits we have seen in patients receiving a single injection of mdHACM into their osteoarthritic knee. Following an extensive review and selection process, we are very excited to have world-class partners who are at the forefront of advancing meaningful medicines; working in collaboration accelerates our ability to gather quality data for our future Biologics License Application (BLA), and our potential to bring tremendous benefit for people living with OA.’ said Dr Robert B. Stein, M.D., Ph.D., MIMEDX President, Regenerative Medicine & Biologics Innovation.

About Image Analysis Group (IAG):

IAG, Image Analysis Group is a unique clinical development partner to life sciences companies. We broadly leverage our proprietary image analysis methodologies, power of our cloud platform DYNAMIKA, years of experience in AI and Machine Learning as well as bespoke co-development business models to ensure higher probability for promising therapeutics to reach the patients. Our independent Bio-Partnering division fuses risk-sharing business models and agile culture to accelerate novel drug development. wp1.ia-grp.com

About MIMEDX: 

MIMEDX is a transformational placental biologics company, developing and distributing placental tissue allografts with patent-protected, proprietary processes for multiple sectors of healthcare. As a pioneer in placental tissue engineering, we have both a commercial business, focused on addressing the needs of patients with acute and chronic non-healing wounds, and a promising late-stage pipeline targeted at decreasing pain and improving function for patients with degenerative musculoskeletal conditions. We derive our products from human placental tissues and process these tissues using our proprietary methods, including the PURION® process. We employ Current Good Tissue Practices, Current Good Manufacturing Practices, and terminal sterilization to produce our allografts. MIMEDX has supplied over two million allografts, through both direct and consignment shipments.

For more information, please reach out to: imaging.experts@ia-grp.com

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The Effects of Weight Loss on Imaging Outcomes in Osteoarthritis of the Hip or Knee in People who are Overweight or Obese: A Systematic Review

Copyright © 2019 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
Osteoarthritis Cartilage. 2020 Jan;28(1):10-21. doi: 10.1016/j.joca.2019.10.013. Epub 2019 Nov 26.

Abstract

OBJECTIVE:
To evaluate the structural effects of weight loss on hip or knee osteoarthritis (OA) and to summarize which structural joint pathologies have been examined and the evidence for the outcome measurement instruments applied.
DESIGN:
Based on a pre-specified protocol (available: PROSPERO CRD42017065263), we conducted a systematic search of the bibliographic databases, Medline, Embase and Web of Science identifying longitudinal articles reporting the effects of weight loss on structural imaging outcomes in OA of the hip or knee in people who are overweight or obese.
RESULTS:
From 1625 potentially eligible records, 14 articles (from 6 cohorts) were included. 2 cohorts were derived from RCTs. Evaluated pathologies were: articular cartilage (n = 7), joint space width (n = 3), bone marrow lesions (n = 5), synovitis (n = 2), effusion (n = 1), meniscus (n = 3), bone marrow density (n = 1) and infrapatellar fat pad (IPFP; n = 2). Cartilage showed conflicting results when evaluating cartilage thickness by direct thickness measurements. Compositional dGEMRIC and T2 mapping measures in early knee OA showed trends towards reduced cartilage degeneration. Joint space width on conventional radiographs showed no change. Weight loss reduced the size of the IPFP. Synovitis and effusion were not affected. Following weight loss DXA showed bone loss at the hip.
CONCLUSION:
We did not find consistent evidence of the effects of weight loss on OA structural pathology in people who are overweight or obese. There is a need to achieve consensus on which structural pathologies and measurements to apply in weight loss and OA research.

The Role of Advanced MRI in the Development of Treat-to-Target Therapeutic Strategies, Patient Stratification and Phenotyping in Rheumatoid Arthritis

In this commentary we discuss the potential of advanced imaging, particularly Dynamic Contrast Enhanced (DCE) magnetic resonance imaging (MRI) for the objective assessment of disease progression in rheumatoid arthritis (RA). We emphasise the potential DCE-MRI in advancing the field and exploring new areas of research and development in RA. We believe that different grades of bone marrow edema (BME) and synovitis in RA can be examined and monitored in a more sensitive manner with DCE-MRI. Future treatments for RA will be significantly improved by enhanced imaging of BMEs and synovitis. DCE-MRI will also facilitate enhanced stratification and phenotyping of patients enrolled in clinical trials.

Development of a Multi-Modality Imaging Approach to evaluate Lupus Nephritis and initial results.

© Author(s) (or their employer(s)) 2019. Published by BMJ.
Annals of the Rheumatic Diseases. 2019 June;78(2)

Abstract

BACKGROUND:
Lupus nephritis (LN) remains a significant cause of morbidity and mortality in subjects with Systemic Lupus Erythematosus (SLE). The gold standard for evaluation of LN remains the kidney biopsy, whereas renal function is usually evaluated by eGFR and urinary protein:creatinine ratio. More effective and sensitive methodology is needed to assess LN and also the response to treatment. Functional imaging of the kidney using quantitative techniques has great potential, as it can assess kidney function and pathologic changes non-invasively by evaluating perfusion, oxygenation, cellular density and fibrosis.
OBJECTIVE:
To develop a multi-modality imaging approach for the evaluation of the spectrum of pathologic changes in LN.

METHODS:

In this multi-center study, subjects who were having a standard of care renal biopsy for LN were asked to participate in the imaging evaluation. Local Institutional Review Board approval was obtained, and subjects signed an Informed Consent Form. Dynamic contrast enhanced MRI (DCE-MRI) was employed to detect changes in vascularization and perfusion, Diffusion Weighted Imaging (DWI) to assess interstitial diffusion, T2*Map/BOLD – the tissue oxygenation and T1rho to evaluate fibrosis. The imaging scores will be compared to renal biopsy, including ISN/RPS classification of LN, activity index and chronicity index.

RESULTS:
Five patients have been evaluated to date and their imaging data assessed for quality. The initial results have demonstrated the feasibility of acquiring multi-modality imaging data, including dynamic imaging sequences, in the multi-center trial setting. Figure 1 illustrates scans from a representative patient. This study will determine whether multi-modality imaging could become an effective, non-invasive tool to assess renal function and pathology in LN.
CONCLUSION:
The initial assessment of 5 LN subjects has established the feasibility of multi-modality imaging as a tool to evaluate LN in a multi-center study. By assessing functional and structural MRI outcomes and correlating them to clinical data, this study will provide essential preliminary evidence on the value of multi-modality imaging in diagnosis and evaluating the response to treatment of LN patients.

A Phase IV, Multicenter, Single-Arm, Open-Label Study to Evaluate the Impact of Apremilast on Hand and Whole-Body MRI Outcomes in Patients with Psoriatic Arthritis (MOSAIC): Rationale, Design, and Methods.

Copyright © Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ
Annals of the Rheumatic Diseases. 2019 June;78(2)_suppl. doi: 10.1136/annrheumdis-2019-eular.1368

Abstract

BACKGROUND:
Phase III clinical trials have shown apremilast (APR) reduced PsA signs/symptoms and improved physical function,but no study has addressed its impact on structural disease progression. MRI is a highly sensitive, validated tool to assess inflammatory and structural changes, as it can detect soft tissue inflammation, bone marrow edema (BME) lesions, bone erosion and proliferation in peripheral joints and axial skeleton. Whole-body (WB)-MRI, a relatively novel technique in musculoskeletal studies, allows assessment of all peripheral/axial joints and entheses in 1 examination. Recent, consensus-based and semi-quantitative scoring methods were developed and validated. This study is the first to systematically use new state-of-the-art MRI scoring methodologies to assess PsA inflammatory and structural changes in a global clinical trial.

OBJECTIVES:
To assess APR efficacy on inflammatory indices and imaging outcome measures associated with PsA structural progression by conventional static MRI and dynamic contrast-enhanced (DCE)-MRI of the most affected hand and WB-MRI.

METHODS:
The study aims to enroll 120 biologic-naïve adults with PsA for ≥3 mos to ≤5 yrs and prior treatment with ≤2 conventional DMARDs. Subjects must have ≥3 swollen and ≥3 tender joints, hand involvement (≥1 swollen joint or ≥1 dactylitis) and ≥1 active enthesitis site. After 4-wk screening, all eligible patients will receive APR 30 mg twice daily (titrated during the first 5 days) as monotherapy or in combination with methotrexate for 48 wks, with a 4-wk observational follow-up. Conventional MRI and optional DCE-MRI of the most affected hand and WB-MRI of the entire body will be performed at Wks 0, 24 and 48. The primary endpoint is change from BL to Wk 24 in OMERACT PsA MRI (PsAMRIS) composite score of BME + synovitis + tenosynovitis. Other imaging endpoints include change from BL to Wk 48 in PsAMRIS composite score (BME + synovitis + tenosynovitis) and change from BL to Wks 24 and 48 in PsAMRIS composite score (BME + synovitis), PsAMRIS composite inflammation score (BME + synovitis + tenosynovitis + periarticular inflammation), PsAMRIS total damage score (erosion + bone proliferation), WB-MRI indices (including peripheral joint inflammation index and peripheral enthesis inflammation index), hip and knee inflammation MRI scores (HIMRISS, KIMRISS), OMERACT heel enthesitis MRI indices, axial inflammation indices (SPARCC, CanDen), DEMRIQ-Volume and DEMRIQ-Inflammation and other DCE-MRI–derived parameters. Clinical parameters will include SJC/TJC, cDAPSA, SPARCC Enthesitis Index, Leeds Enthesitis Index, Leeds Dactylitis Index, PASDAS, PtGA, PhGA, Patient’s Assessment of Pain, HAQ-DI, and BASDAI and impact of disease (PsAID12). Safety and tolerability also will be assessed.

RESULTS:
The study protocol was approved by an independent ethics committee and is now enrolling in the USA. Selected countries in Europe and Russia will also participate. MRI, clinical and patient-reported outcomes will be analyzed.

CONCLUSION:
This study will provide important evidence of APR’s impact on inflammatory/structural changes by assessing all PsA musculoskeletal domains (peripheral arthritis, enthesitis, dactylitis and axial disease). Furthermore, it will yield information on use of conventional MRI–, WB-MRI– and DCE-MRI–driven outcome measures in PsA clinical trials.