Gout is a form of arthritis — an inflammation of the joints — that causes sudden, severe attacks of pain, tenderness, redness, warmth, and swelling in some joints. Imaging modalities that have clinical relevance in gout include conventional radiography (CR), ultrasonography (US), computed tomography (CT), dual energy computed tomography (DECT), magnetic resonance imaging (MRI) and nuclear medicine.

In clinical trials, imaging biomarkers are used to assess joint inflammation and to be more specific about including a patient intro the trial, as imaging is more specific to and even pathognomonic of gout.

IAG’s team is actively working with drug developers to determine and help including into the trial inclusion / exclusion criteria, the right methodologies for patient stratification that can help differentiating gout from other inflammatory arthritis conditions. This especially critical for novel therapeutics targeting early disease.

IAG’s team has extensive expertise in using in CR, US and DECT to assist in monitoring response to treatment.

DECT provides good diagnostic accuracy for detection of monosodium urate (MSU) deposits in patients with gout. However, sensitivity is lower in patients with recent-onset disease. DECT can have a significant impact on clinical decision making when gout is suspected, but fails to demonstrate inflammatory potential of the MSU deposits.

IAG team is very active in scientific community and recent work was focused on completing an MRI trial assessing the response of sub-clinical, synovial inflammation to nine months of urate lowering therapy (ULT). Sub-clinical synovial-based inflammation has been documented in inter-critical gout. Together with academic and medical colleagues, we have investigated and reported a significant reduction in serum urate levels and when the MRI data was analysed with a quantitative method, we were able to score inter-critical synovitis in the MRI data in gout patients.

IAG team brings a great site network and significant experience in working with:

• DECT
• CT
• MRI, inc Contrast MRI
• US
• PET

To support novel drug development for patients with gout. Reach out to our expert team, as you are designing and planning your trial.

About IAG, Image Analysis Group

IAG, Image Analysis Group is a strategic partner to bio-pharmaceutical companies developing new treatments to improve patients’ lives. Our dynamic Strategy, Trial Solutions and Bio-Partnering divisions work closely to meet critical needs of biotechnology companies: funding, clinical development, and monetization of their assets. We fuse decades of therapeutic insights, risk-sharing business model and agile culture to accelerate novel drug development. IAG broadly leverages its core imaging expertise, proprietary technology platform DYNAMIKA and capabilities to support an objective early go no/ go decision and drive excellence for tomorrow’s innovative therapeutic agents with speed.

Contact our expert team: imaging.experts @ ia-grp.com

Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect multiple different organs, including the kidneys and central nervous system. With lupus, the body’s immune system targets its own body tissues. Lupus arthritis affects hands of the patients and lupus nephritis – the kidneys.

IAG’s team is supporting a number of academic and proof of concept trials that develop, test and validate various radiologic methods aiming to improve disease characterization in patients with SLE beyond simple anatomical endpoints.

In clinical trials, imaging biomarkers are used to assess joint inflammation and to be more specific about including a patient intro the trial, as imaging is more specific when added to the clinical assessment.

IAG’s team is actively working with drug developers to determine and help including into the trial inclusion / exclusion criteria, the right methodologies for patient stratification that can help differentiating lupus patients. This especially critical for novel therapeutics targeting early disease.

IAG’s team supported trials that involved various radiological examinations of patients with lupus, such as

• Computed tomography (CT),
• Magnetic Resonance Imaging (MRI),
• Ultrasound (US).

IAG’s team is active in scientific community and have contributed and actively led the developments in physiological non-contrast MRI protocols to assess tissue oxygenation, glomerular filtration, renal perfusion, interstitial diffusion, and inflammation-driven fibrosis in lupus nephritis (LN) patients. Pour radiology team worked on the vessel size imaging (VSI, an MRI approach utilizing T2-relaxing iron oxide nanoparticles) development and nuclear medicine team on the molecular imaging probes used to monitor the disease.

Reach out to our expert team, as you are designing and planning your trial.

About IAG, Image Analysis Group

IAG, Image Analysis Group is a strategic partner to bio-pharmaceutical companies developing new treatments to improve patients’ lives. Our dynamic Strategy, Trial Solutions and Bio-Partnering divisions work closely to meet critical needs of biotechnology companies: funding, clinical development, and monetization of their assets. We fuse decades of therapeutic insights, risk-sharing business model and agile culture to accelerate novel drug development. IAG broadly leverages its core imaging expertise, proprietary technology platform DYNAMIKA and capabilities to support an objective early go no/ go decision and drive excellence for tomorrow’s innovative therapeutic agents with speed.

Contact our expert team: imaging.experts @ ia-grp.com

Neuromuscular disorders affect the nerves that control voluntary muscles and the nerves that communicate sensory information back to the brain. Nerve cells send and receive electrical messages to and from the body to help control voluntary muscles. When the neurons become unhealthy or die, communication between the nervous system and muscles breaks down. As a result, muscles weaken and waste away (atrophy).

IAG’s experience with neuromuscular disorders include clinical development in:

• Amyotrophic lateral sclerosis (ALS)
• Multiple sclerosis
• Muscular dystrophy
• Myasthenia gravis
• Myopathy
• Myositis
• Peripheral neuropathy
• Spinal muscular atrophy

With the use of imaging biomarkers, our team helps to support a PI / physician in patient selection and disease diagnosis. As alternative to invasive methods, we recommend and help integrating into the trials Magnetic resonance imaging (MRI) scan of the brain, spinal cord, thigh or upper arm or Ultrasound (US), when appropriate.

MRI is a non-invasive imaging method, without ionizing radiation, which has the ability to visualize muscle, fat, connective tissue and bone. MRI has several advantages over muscle ultrasound, including that MRI has minimal operator-dependence and allows for excellent visualization of all muscles.

Added advantage of using MRI that we can provide the measurements for both volume and perfusion of muscle can be extracted from the scans.

Some of the studies that we support are investigating the disease changes at molecular level. IAG’s team has extensive experience in using PET / SPECT to reveal the metabolism of glucose within the bone and joint system.

IAG team is closely working with the recruiting sites and ensures seamless imaging data flow and assessment, to best support the development of novel treatments for these challenging conditions.

Our team is active in scientific community and our recent work investigates the association between pain and muscle perfusion, giving rise to many scientific collaborations. Our academic partners are working on the methodologies which allow for automated measurements of Fat Fraction and Muscle Volume. In any of our trials, the medical image analysis will be conducted with DYNAMIKA, that brings together quantitative methodologies for understanding treatment induced changes.

About IAG, Image Analysis Group

IAG, Image Analysis Group is a strategic partner to bio-pharmaceutical companies developing new treatments to improve patients’ lives. Our dynamic Strategy, Trial Solutions and Bio-Partnering divisions work closely to meet critical needs of biotechnology companies: funding, clinical development, and monetization of their assets. We fuse decades of therapeutic insights, risk-sharing business model and agile culture to accelerate novel drug development. IAG broadly leverages its core imaging expertise, proprietary technology platform DYNAMIKA and capabilities to support an objective early go no/ go decision and drive excellence for tomorrow’s innovative therapeutic agents with speed.

Contact our expert team: imaging.experts @ ia-grp.com

Psoriatic arthritis (PsA) is a heterogeneous inflammatory rheumatologic disorder characterized by peripheral arthritis, affecting 6% to 39% of patients suffering from psoriasis. PsA is classified as a seronegative spondyloarthropathy (SpA) because it shares certain features with other conditions included in that group. Indeed, spinal involvement has been reported in approximately 50% of patients with PsA. In addition, PsA is associated with enthesitis and dactylitis, which are extra-articular features common to SpA. Finally, the majority of patients with PsA are negative for the rheumatoid factor.

At the onset, the disease is typically oligoarticular, but can develop into asymmetrical polyarthritis. Merely 10% of patients present with articular and cutaneous changes simultaneously. In a half of patients, arthritis precedes psoriasis. In the initial stages of the disease, synovitis is usually observed in the knee, ankle, and metatarsophalangeal (MTP) joints and occurs in conjunction with dactylitis. Sternoclavicular joints are typically involved.

IAG’s team has extensive expertise and track record in supporting the development of novel therapeutics in PsA and SpA and helping to take these drugs from early phase all the way to phase 3 and approval. Currently IAG is supporting one of the largest and scientifically driven trials (MOSAIC). Our expertise is in use of

• X-ray
• MRI
• US
• CT

to support disease diagnosis and assessment of treatment response.

IAG’s team plays an active role in the scientific community and have led the development of novel scoring systems for early assessment of synovial inflammatory changes, quantification of inflammation and quantitative assessment of erosive changes.

Our extensive experience in using radiography, which is a conventional gold standard method for assessment of structural damage in spine and sacroiliac joints. We recommend and assure optimal use of Magnetic resonance Imaging (MRI) that has a number of advantages over plain radiography and ultrasound in assessing disease activity and damage in peripheral joints in PsA. MRI features of PsA include synovitis, dactylitis, tenosynovitis, erosions, bone edema and enthesitis. MRI and anatomic studies have helped researchers develop the concept of synovio-entheseal complex in the pathogenesis of PsA. IAG’s scientific team is actively developing and integrating into the trials novel sequences, including

• Ultrashort T2 echo for assessment of entheses will help in understanding the similarities and differences between mechanical and inflammatory entheseal changes.
• Whole-body MRI (WB MRI), with OMERACT as part of novel clinical development.
• Dynamic contract enhanced MRI for quantitative assessment of inflammation.
• Quantitative assessment of erosions.

About IAG, Image Analysis Group

IAG, Image Analysis Group is a strategic partner to bio-pharmaceutical companies developing new treatments to improve patients’ lives. Our dynamic Strategy, Trial Solutions and Bio-Partnering divisions work closely to meet critical needs of biotechnology companies: funding, clinical development, and monetization of their assets. We fuse decades of therapeutic insights, risk-sharing business model and agile culture to accelerate novel drug development. IAG broadly leverages its core imaging expertise, proprietary technology platform DYNAMIKA and capabilities to support an objective early go no/ go decision and drive excellence for tomorrow’s innovative therapeutic agents with speed.

Contact our expert team: imaging.experts @ ia-grp.com

Ankylosing Spondylitis (AS), a form of spondylarthritis (SpA), is a systemic inflammatory rheumatic disease. Although the exact pathogenesis of AS is not yet fully understood, as with rheumatoid arthritis, the swelling, pain, and joint damage that characterize AS are considered to be the result of complex autoimmune and inflammatory processes based on both environmental and genetic factors.

IAG’s team has extensive expertise and track record in supporting the development of novel therapeutics in AS and SpA and helping to take these drugs from early phase all the way to phase 3 and approval. Our expertise is in use of

• X-ray
• MRI
• Dynamic Contrast Enhanced MRI
• CT

to support disease diagnosis and assessment of treatment response.

IAG’s team plays an active role in the scientific community and have led the development of novel scoring systems for early assessment of synovial inflammatory changes, quantification of inflammation and quantitative assessment of erosive changes. Our extensive experience in using radiography, which is a conventional gold standard method for assessment of structural damage in spine and sacroiliac joints. Our medical science team have worked with drug developers in trials incorporating Computed Tomography (CT), which is a more sensitive method for assessment of structural changes in the spine and sacroiliac joints.

In many trials, early diagnosis of sacroiliitis, the most frequent clinical symptom often accompanied by inflammatory back pain, and other inflammatory lesions of the spine such as spondylitis and spondylodiscitis, can be visualized early by magnetic resonance imaging (MRI), especially using fat saturating STIR or Gd-Enhanced Dynamic MRI sequences. IAG’s team helped to integrate ultrasonography and MRI into the trials for visualization and quantification of peripheral arthritis and enthesitis.

 

About IAG, Image Analysis Group

IAG, Image Analysis Group is a strategic partner to bio-pharmaceutical companies developing new treatments to improve patients’ lives. Our dynamic Strategy, Trial Solutions and Bio-Partnering divisions work closely to meet critical needs of biotechnology companies: funding, clinical development, and monetization of their assets. We fuse decades of therapeutic insights, risk-sharing business model and agile culture to accelerate novel drug development. IAG broadly leverages its core imaging expertise, proprietary technology platform DYNAMIKA and capabilities to support an objective early go no/ go decision and drive excellence for tomorrow’s innovative therapeutic agents with speed.

Contact our expert team: imaging.experts @ ia-grp.com

Osteoarthritis (OA) is considered to be a disease of the cartilage in the joints even though it involves the whole joint, including the bone and synovium (thin lining of the joints which produces synovial fluid). With time, more and more of the cartilage is destroyed by the disease with inflammation commonly occurring. The treatment of knee OA is currently restricted to management of pain and function with low-to-moderate efficacy. A number of pain medications is being developed and already approved. To be registered as a DMOAD, companies must demonstrate their drug candidates alter the structural progression of OA. The FDA and the European Medicines Agency’s Committee for Medicinal Products for Human Use have DMOAD development guidelines and although considerable time has passed since their issue (FDA draft guidance in 1999, CHMP guidance in 2010), they are still in effect today.

In 2010, a Structural Change Working Group from The Osteoarthritis Research Society International (OARSI) provided recommendations to the FDA concerning finalizing the its 1999 draft guidance (at the FDA’s request), but a final guidance document was never issued.

The FDA’s draft guidance and CHMP’s guidance state that the only acceptable primary endpoint for DMOAD pivotal studies is Joint Space Narrowing (JSN, preferably of the knee or hip), measured by X-ray.

JSN is defined as decreasing Joint Space Width (JSW) and represents a surrogate measure for the thickness of cartilage in a joint.

Both guidance documents outline what pivotal study parameters are required for drugs to carry either a label for “treatment of symptoms” or “structure modifying/delay in structural progression” (contact our team for further information).

Developers are also required by both agencies to demonstrate that a DMOAD should have an effect on both structure and patient-reported clinical benefit (symptoms and/or function). The effects of a potential DMOAD on symptom modification may be assessed in a separate clinical trial of shorter duration.

…though there are some limitations to JSN…

 

Although JSN is still the mandatory primary endpoint for structural modification, we note that it does have limitations, some of which present challenges to developers:

• JSN changes are generally slow and variable between subjects, necessitating large and lengthy clinical trials;
• It is difficult to obtain high quality reproducible X-rays of joints despite standardization of protocols to reduce variability in joint positioning;
• OA is a disease that affects multiple tissues within a joint and is not purely the loss of cartilage. JSN by X-ray cannot visualize cartilage or other tissues and therefore potential early beneficial changes in joint tissues may be missed when using JSN alone; and
• It remains unclear what change in JSN is clinically relevant to a patient. A number of agents (including glucosamine and chondroitin sulphate) have demonstrated superior JSN vs. placebo, but with either no or clinically irrelevant improvement in symptoms/function.

… MRI is becoming increasingly important

In the last two decades, there have been significant advances in magnetic resonance imaging (MRI) within the OA field. The primary attraction of MRI in OA is the ability to analyze multiple tissues of a joint, with the possibility of detecting structural changes early in the disease process.

In the OARSI Structural Change Working Group’s 2010 review of FDA guidance, it was recommended that MRI be used in clinical trials for cartilage morphology assessment and that the study of all joint tissues (possible by MRI) is important.

However, the Group acknowledged that a greater understanding of cartilage change quantitation, performance metrics of non-cartilage features and correlations of morphological changes with symptoms were needed, a view shared by the CHMP in its 2010 guidelines.

We believe that the successful use of MRI-based secondary endpoints in DMOAD development will strengthen a marketing application where JSN is the primary endpoint for structural modification. With continued growth in MRI research in OA, it is feasible that an MRI primary endpoint will be adopted in the future.

…as evidenced by Phase II trials of potential DMOADs

We note that three of the potential DMOADs in the OA Phase II clinical pipeline are being evaluated in clinical trials with an MRI-based primary endpoint, suggesting developers prefer MRI to JSN by x-ray for an initial assessment of drug efficacy.

For a symptom relief label, WOMAC has supported the most recent approval

Some early studies may consider using KOOS

IAG’s team has extensive experience in supporting OA drug development. Our team plays an active role in the scientific community and have led the development of novel scoring systems and formed strong collaborations with the industry’s Key Opinion Leaders as well as regulatory consultants and agencies.

We bring deep knowledge to help designing a trials, global experienced operations team and fully integrated cloud platform to support a trial that may require use of:

• Xray
• MRI
• Dynamic Contrast Enhanced MRI
• CT
• PET / CT

About IAG, Image Analysis Group

IAG, Image Analysis Group is a strategic partner to bio-pharmaceutical companies developing new treatments to improve patients’ lives. Our dynamic Strategy, Trial Solutions and Bio-Partnering divisions work closely to meet critical needs of biotechnology companies: funding, clinical development, and monetization of their assets. We fuse decades of therapeutic insights, risk-sharing business model and agile culture to accelerate novel drug development. IAG broadly leverages its core imaging expertise, proprietary technology platform DYNAMIKA and capabilities to support an objective early go no/ go decision and drive excellence for tomorrow’s innovative therapeutic agents with speed.

Contact our expert team: imaging.experts @ ia-grp.com