Musculoskeletal Diseases

All Conditions

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Immune System Diseases

Arthritis

Necrosis

Arthritis, Rheumatoid

Joint Diseases

Rheumatic Diseases

Collagen Diseases

Connective Tissue Diseases

Autoimmune Diseases

Central Nervous System Depressants

All Drugs and Chemicals

Anti-Inflammatory Agents

Antirheumatic Agents

Anesthetics

Antibodies

Immunoglobulins

Certolizumab Pegol

Immunoglobulin Fab Fragments

Tumor Necrosis Factor Inhibitors

Immunosuppressive Agents

Immunologic Factors

Certolizumab Pegol (CZP) liquid formulation 200 mg sc -(initial loading dose of 400 mg sc at 0 (Baseline), 2, and 4 weeks), then 200 mg sc every 2 weeks at 6, 8, and 10 weeks with arthroscopic synovial tissue biopsy pre- and post-treatment.

CZP is an anti-TNF, humanized antibody Fab' fragment/polyethylene glycol(PEG)conjugate. CZP liquid formulation 200 mg sc -(initial loading dose of 400 mg sc at 0 (Baseline), 2, and 4 weeks), then 200 mg sc every 2 weeks at 6, 8, and 10 weeks.

Certolizumab Pegol (CZP)

Subjects will undergo arthroscopy Pre and Post Treatment. The arthroscopy will be performed on a clinically inflamed joint. A single arthroscopy procedure using a small bore arthroscope will be conducted to obtain synovial tissue in each joint in all subjects. Local anesthesia will be used only. Two small incisions will be made to accommodate the arthroscope and other instruments. Synovial biopsies will be obtained using a motorized shaver.

Arthroscopic synovial tissue biopsy

Nathan Wei, MD,FACP,FACR

The purpose of this study is to conduct an Investigator-Sponsored Study to determine the potential immunomodulatory effects of Certolizumab Pegol (CZP) treatment at the site of disease activity (synovial lining) in subjects with rheumatoid arthritis (RA), using pre treatment and post treatment arthroscopic synovial biopsies and ex vivo on gene expression.

Rheumatoid Arthritis Treatment and Biopsy Study Assessing Certolizumab Pegol (Cimzia)

Open-Label Pre and Post Treatment Arthroscopic Synovial Biopsy Study for the Assessment of Certolizumab Pegol Immunomodulatory Synovial Effects on Select Biomarkers and Gene Expression

Synovial tissue biopsy samples were taken at baseline and at 12 weeks after starting treatment with CZP. These samples were analyzed to determine the concentrations of select biomarkers and to determine the percent change in concentration from baseline to week 12.

The DAS 28 ESR is a score calculated from the results of a 28-count joint assessment (total number of tender joint possible is 28, and total number of swollen joints possible is 28), the Erythrocyte Sedimentation Rate (ESR), and the Patient Global Assessment (measured using a 100 mm visual analogue scale, with the lowest possible score of 0 mm meaning the subject is not affected at all by arthritis and the highest possible score of 100 mm meaning the subject is severely affected by arthritis). A lower DAS 28 ESR indicates less active disease, and a higher DAS 28 ESR indicates more active disease. The DAS 28 ESR was calculated for each subject at the screening visit and at the Week 14 final visit. The percent change was then calculated for each patient, and a mean percent change for all subjects was determined.

University of California, San Diego

Nathan Wei, MD, FACP, FACR:

Nathan Wei, MD, FACP, FACR

Certolizumab Pegol (CZP) liquid formulation 200 mg sc -(initial loading dose of 400 mg sc at 0 (Baseline), 2, and 4 weeks), then 200 mg sc every 2 weeks at 6, 8, and 10 weeks.

Certolizumab Pegol (CZP): CZP is an anti-TNF, humanized antibody Fab' fragment/polyethylene glycol(PEG)conjugate. CZP liquid formulation 200 mg sc -(initial loading dose of 400 mg sc at 0 (Baseline), 2, and 4 weeks), then 200 mg sc every 2 weeks at 6, 8, and 10 weeks.

Arthroscopic synovial tissue biopsy: Subjects will undergo arthroscopy Pre and Post Treatment. The arthroscopy will be performed on a clinically inflamed joint. A single arthroscopy procedure using a small bore arthroscope will be conducted to obtain synovial tissue in each joint in all subjects. Local anesthesia will be used only. Two small incisions will be made to accommodate the arthroscope and other instruments. Synovial biopsies will be obtained using a motorized shaver.

>18 years of age

Age, Customized

Sex: Female, Male

United States

Region of Enrollment

All subjects who meet screening criteria were enrolled until target number of 12 subjects was met.

Nathan Wei, MD

TNFa

CXCL13

IL-8

IL-6

IL-1b

IL-10

IP-10

BCL3

CD3E

DUSP4

FOXP3

CD79A

CD138

MMP-3

MMP-1

Percent Change From Baseline in Synovial TNFa, CXCL13, IL-8, IL-6, IL-1b, IL-10, IP-10, BCL3, CD3E, DUSP4, FOXP3, CD79A, CD138, MMP-3, and MMP-1 After 12 Weeks of Treatment With Certolizumab Pegol (CZP) in Patients With Rheumatoid Arthritis

Percent Change From Screening in Disease Activity Score (DAS) 28 ESR After 14 Weeks of Treatment

Certolizumab Pegol (CZP) liquid formulation 200 mg sc -(initial loading dose of 400 mg sc at 0 (Baseline), 2, and 4 weeks), then 200 mg sc every 2 weeks at 6, 8, and 10 weeks.

Certolizumab Pegol (CZP): CZP is an anti-Tumor Necrosis Factor (TNF), humanized antibody Fab' fragment/polyethylene glycol(PEG)conjugate. CZP liquid formulation 200 mg sc -(initial loading dose of 400 mg sc at 0 (Baseline), 2, and 4 weeks), then 200 mg sc every 2 weeks at 6, 8, and 10 weeks.

Arthroscopic synovial tissue biopsy: Subjects will undergo arthroscopy Pre and Post Treatment. The arthroscopy will be performed on a clinically inflamed joint. A single arthroscopy procedure using a small bore arthroscope will be conducted to obtain synovial tissue in each joint in all subjects. Local anesthesia will be used only. Two small incisions will be made to accommodate the arthroscope and other instruments. Synovial biopsies will be obtained using a motorized shaver.

Overall Study

Digestive System Diseases

Crohn Disease

Intestinal Diseases

Inflammatory Bowel Diseases

Gastroenteritis

Gastrointestinal Diseases

Other Dietary Supplements

Benzocaine

Tannic Acid

The active Hyperbaric Oxygen Therapy (HBOT) arm will receive 100% oxygen at 2.0-2.5 atmospheres (ATM).

The standard of care for perianal Crohn's disease (PCD) involves conventional therapies such as immunosuppressive agents and biologics, which can be used to induce and maintain fistula remission. Tumor necrosis factor (TNF) antagonists are considered the first-line therapy for PCD, and clinical trial evidence supports their efficacy in achieving short-term fistula remission.

Oxygen Gas for Inhalation

The accepted standard of care for perianal Crohn's disease (PCD) involves conventional therapies such as immunosuppressive agents and biologics, which can be used to induce and maintain fistula remission.

Standard of care

Jeffrey McCurdy, MD

Jennifer Kong, MPH

This study aims to test a new treatment called hyperbaric oxygen therapy (HBOT) for a severe type of inflammatory bowel disease called perianal Crohn's disease (PCD). PCD causes painful perianal infections and chronic drainage from fistula tracts, and current treatments are only moderately effective and may not be suitable for all patients. HBOT is a safe and commonly used treatment for chronic non-healing wounds and other conditions. Previous studies have suggested that HBOT may help heal fistulas in PCD patients, but these studies were small and lacked controls.

Hyperbaric oxygen therapy (HBOT) is an effective intervention for improving healing of chronic wounds. HBOT involves the delivery of 100% oxygen in a pressurized environment, typically two to three times standard atmospheric pressure at sea level (2.0-2.5 ATA). This results in increased oxygen tension in plasma and promotes the diffusion of oxygen into tissue, which stimulates tissue restorative pathways that are essential for wound healing16. Hyperoxia also modulates the immune system by suppressing proinflammatory cytokines and promoting the production of anti-inflammatory cytokines. It also enhances the production of growth factors, mobilize stem cells, and stimulates anti-microbial pathways, all of which are believed to be central mechanisms involved in the repair of damaged tissue in IBD. The safety profile of HBOT is also excellent, with a reported adverse event incidence of 10 per 10,000. The most reported adverse event is middle ear barotrauma, which is minor and not life threatening.

There is emerging evidence that HBOT may be an effective treatment option for perianal Crohn's disease (PCD). To date, 10 observational studies with a total of 118 patients with PCD refractory to conventional therapy have assessed the effectiveness and safety of HBOT (McCurdy et al., IBDJ 2021). In this small number of patients, HBOT resulted in high rates of clinical response (75% \[95% CI, 66%-83%; I2, 0\]) and clinical remission (55% \[95% CI, 44%-65%; I2, 61\]) (Figure 1). Additionally, the HOT-TOPICs study, an open-label observational study demonstrated that HBOT was associated with radiologic improvement of fistula tracts as shown by a reduction in the modified Van Assche MRI score from 9.2 (95% CI, 7.3-11.2) to 7.3 (95% CI, 6.9-9.7). Despite these encouraging results, formal controlled clinical trials have not yet been conducted in patients with PCD to determine the true clinical impact of HBOT in this disease.

A prospective, multicenter, randomized open-label clinical trial and parallel registry.

Hyperbaric Oxygen Therapy for Perianal Fistulizing Crohn's Disease Not Responsive or Intolerant to Conventional Care: HYPNOTIC Pilot Study

Primary outcome for phase 1 is the rate of recruitment. Recruitment is defined as the number of randomized patients that receive at least one treatment (active HBOT or control) per year. After one year, recruitment of 20 patients or more (an average of 4 patients per site) will be considered acceptable to proceed to phase 2 without a requirement for modifications, recruitment of 10-20 patients will suggest minor modifications to the protocol are required and recruitment of less than 10 patients will suggest major modifications to the protocol are required prior to proceeding to phase 2.

The primary outcome for phase 2 is the proportion of patients who achieve combined remission of perianal fistulizing Crohn's Disease at week 12 defined as closure of all external openings by finger compression test, and an absence of collections \>2 cm confirmed by MRI assessment assessed at 8-12 weeks. MRI pelvis is the optimal outcome measure for measuring response to treatment as it has been shown to be the most accurate test for predicting long-term outcomes.

Ottawa Hospital Research Institute

Nervous System Diseases

Behaviors and Mental Disorders

Rare Diseases

Inflammation

Dementia

Mental Disorders

Alzheimer Disease

Cognitive Dysfunction

Brain Diseases

Psychotic Disorders

Central Nervous System Diseases

Neurodegenerative Diseases

Tauopathies

Neurocognitive Disorders

Cognition Disorders

Familial Alzheimer Disease

1.0 mg/kg XPro1595 will be administered via subcutaneous injection once a week for 12 weeks.

1.0 mg/kg of Placebo will be administered via subcutaneous injection once a week for 12 weeks.

XPro1595 will be delivered by subcutaneous injection once a week.

XPro1595

Placebo will be delivered by subcutaneous injection once a week

Placebo

Tara Lehner

The goal of this Phase 2 MCI study is to determine whether 1.0 mg/kg XPro1595 is superior to placebo at improving measures of cognition, functioning and brain quality in individuals with MCI and biomarkers associated with neuroinflammation (APOE4) and to evaluate safety, tolerability, and efficacy of XPro1595.

This study is designed as a Phase 2, double-blind randomized, placebo-controlled study investigating the safety, tolerability, and efficacy of XPro1595 in patients with MCI. The planned dose is 1.0 mg/kg of XPro1595 and matching placebo.

* (2:1) XPro1595 (1mg/kg), placebo
* Weekly subcutaneous injections

Study to Assess the Efficacy of XPro1595 in Patients With Mild Cognitive Impairment With Biomarkers of Inflammation

A Phase 2, Randomized, Placebo-Controlled, Double-Blind Study of XPro1595 in Patients With Mild Cognitive Impairment (MCI) With Biomarkers of Inflammation

Change in Goal Attainment Scale (GAS)

The achievement of each goal is rated on a 5-point attainment scale (-2, -1, 0, +1, +2) to allow standardized scoring of personalized outcomes. A participant's overall goal attainment is quantified using a formula that takes into account the number of goals that have been set, and the extent to which they are correlated with each other. For each identified goal area, the caregiver will be asked to give a detailed description of the patient's current (baseline) status and goal status, which will be recorded at the -1 and 0 levels on the 5-point scale, respectively. The remaining levels of the scale will then be set: somewhat better than the goal (+1), much better than the goal (+2), and much worse than the goal (-2).

To evaluate the effect of XPro1595 compared with placebo on goal attainment scores

Change from Screening to Week 12 in activity metrics (time spent lying, sitting, standing, stepping, upright, in walking bouts, in-context specific walking bouts; number of steps, and sit-to-stand transitions) as measured by the activity monitor. Physical activity will be measured in real time using the activity monitor worn on the patient's wrist. Total activity counts per minute (higher activity counts = more activity) and number of steps taken will be derived from data. Patients will be equipped with the monitoring device during the screening period and activity metrics will be measured for 7 days prior to each EMACC assessment. Data will be measured at Screening, Week 1, Week 3, Week 6, Week 9 and Week 12.

To assess the effect of XPro1595 compared to placebo on measures of activity

The Multidimensional Psychological Questionnaire (MPsQ) questionnaires have been designed to specifically measure patient personality characteristics associated with the placebo response. The MPsQ questionnaires are self-reported, and each item is rated on a 5-point scale ranging from 1 (strongly disagree) to 5 (strongly agree).

MPsQs will be completed by the patient and separate MPsQs will be completed by the study partner at screening.

MPsQs will be completed by the patient and separate MPsQs will be completed by the study partner prior to investigational product administration.

The patient and study partner will complete MPsQs at Screening and Week 1.

To measure patient personality characteristics associated with the placebo response.

Change from Baseline to Week 12 in the Early and Mild Alzheimer's Cognitive Composite (EMACC) (Jaeger 2017) made up of the following tests:

* International Shopping List Test- Immediate recall (Word List Learning Test-Immediate recall)
* Trail Making Test Part A and B
* Digit Symbol Coding Test
* Digit Span Forward and Backward
* Category Fluency Test (DKEFS)
* Letter Fluency Test (DKEFS)

To assess the efficacy of XPro1595 compared with placebo on cognitive performance in patients with MCI

Change from Screening to Week 12 in Cogstate Composite mean score.

Cogstate is a brief, computerized, neuropsychological battery to evaluate cognitive impairments in mild cognitive impairment (MCI), and Alzheimer's disease (AD). CogState assesses attention and memory functions - including Information processing speed, Visual attention, Working memory and Visual learning. Cogstate scores are measured on a linear scale (with no maximum score). A reduction in scores compared to baseline signifies an improvement in cognitive functions.

The Cogstate battery will be administered at Screening and each week for 12 weeks.

To assess the efficacy of XPro1595 compared with placebo on cognitive performance in patients with MCI

Change from Screening to Week 12 in myelin content.

Change from Screening to Week 12 in blood inflammatory and neurodegeneration biomarkers (on blood inflammatory and neurodegeneration biomarker amyloid)

To assess the efficacy of XPro1595 compared with placebo on blood inflammatory and neurodegeneration biomarkers (on blood inflammatory and neurodegeneration biomarker amyloid)

Change from Screening to Week 12 in blood inflammatory and neurodegeneration biomarkers (on blood inflammatory and neurodegeneration biomarker pTau)

To assess the efficacy of XPro1595 compared with placebo on blood inflammatory and neurodegeneration biomarkers (on blood inflammatory and neurodegeneration biomarker pTau)

Change from Screening to Week 12 in MRI neuroinflammation (White matter Free Water)

To assess the efficacy of XPro1595 compared with placebo on imaging neuroinflammation

Change from Screening to Week 12 in regional brain glucose uptake as measured by F-fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) scans

Alzheimer's Disease (AD) is characterized by a chronic brain glucose deficit. White matter glucose deterioration is also evident in Mild Cognitive Impairment (MCI) and specific to limbic fascicles. We will quantify the change in regional brain glucose uptake for gray matter and white matter tracts using PET imaging and the F-fluorodeoxyglucose (FDG) radiotracer. PET maps will be registered to Magnetic Resonance (MR) anatomical images and corrected for partial volume effect. Standard uptake value ratios (SUVr) will be calculated using the cerebellum as a reference region.

FDG-PET scans will be performed at Screening and Week 12.

To assess the efficacy of XPro1595 compared with placebo on imaging markers of brain quality

Change from Baseline to Week 12 in MRI Apparent Fiber Density (AFD)

To assess the efficacy of XPro1595 compared with placebo on axonal integrity in patients with MCI

Change from Screening to Week 12 in Neuropsychiatric Inventory (NPI-12) study partner items

To assess the effect of XPro1595 compared with placebo on non-cognitive behavioral symptoms in patients with MCI

Change from Screening to Week 12 in brain activity as measured by electroencephalogram (EEG) scans (Change in brain activity as measured by the EEG in microvolts).

Specifically, a series of EEG markers previously associated with AD (Horvath et al. 2018) including high and low frequency band powers, the P300, and Mismatch Negativity (MMN) event-related potentials will be evaluated.

An EEG scan will be administered at Screening and each week for 12 weeks.

To assess the efficacy of XPro1595 compared with placebo on brain activity in patients with MCI

Change from Baseline to Week 12 in language and speech patterns using Winterlight Labs analysis

To assess the effect of XPro1595 compared with placebo on speech and language in patients with MCI

Change from Screening to Week 12 in Alzheimer's Disease Cooperative Study - Mild Cognitive Impairment Activities of Daily Living (ADCS-MCI ADL)

The 23-item ADCS-MCI-ADL Scale has good test-retest reliability, will be utilized to assess performance functioning in MCI patients (Galasko et al., 1997; Douglas Galasko et al., 2006; Pedrosa et al., 2010). The ADCS-ADL includes 18 items from traditional basic ADL scales and 5 items from instrumental activities of daily living scales (IADL) The possible range of total scores for the ADL Scale is 0-53 and higher scores indicate better functioning. The internal reliability was .91( Galasko et al., 1997; Douglas Galasko et al., 2006; Pedrosa et al., 2010).

The ADCS-MCI ADL will be performed at Screening and Week 12.

To assess the effect of XPro1595 compared with placebo on Activities of Daily Living (ADL) in patients with MCI

Change from Screening to Week 12 in Clinical Dementia Rating Scale Sum of Boxes (CDR-SB)

The CDR scale is a clinician-rated dementia staging system that tracks the progression of cognitive impairment in 6 categories (memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care). Each category is scored on a 5-point scale in which None = 0, Questionable = 0.5, Mild = 1, Moderate = 2, and Severe = 3. The global CDR score is established by clinical scoring rules and has values of 0 (no dementia), 0.5, (questionable dementia), 1 (mild dementia), 2 (moderate dementia), and 3 (severe dementia). The Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) is obtained by adding the ratings in each of the 6 categories and ranges from 0 to 18 with higher scores indicative of greater impairment.

To assess the effect of XPro1595 compared with placebo on cognition and global function in patients with MCI

Clinically significant abnormalities of laboratory values, physical findings, electrocardiogram findings and other safety assessments will be recorded as adverse events if the findings meet the defined criteria for adverse events.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Rheumatoid Arthritis Treatment and Biopsy Study Assessing Certolizumab Pegol (Cimzia)	NCT01374971	Rheumatoid Arth...	Certolizumab Pe... Arthroscopic sy...	18 Years -	Arthritis Treatment Center, Maryland
Rheumatoid Arthritis Treatment and Biopsy Study Assessing Certolizumab Pegol (Cimzia)	NCT01374971	Rheumatoid Arth...	Certolizumab Pe... Arthroscopic sy...	18 Years -	Arthritis Treatment Center, Maryland
Hyperbaric Oxygen Therapy for Perianal Fistulizing Crohn's Disease Not Responsive or Intolerant to Conventional Care: HYPNOTIC Pilot Study	NCT06109961	Inflammatory Bo...	Oxygen Gas for ... Standard of car...	17 Years -	Ottawa Hospital Research Institute
Study to Assess the Efficacy of XPro1595 in Patients With Mild Cognitive Impairment With Biomarkers of Inflammation	NCT05321498	Mild Cognitive ... Alzheimer Disea... Dementia Brain Diseases Central Nervous... Nervous System ... Tauopathies Neurodegenerati... Mental Disorder...	XPro1595 Placebo	55 Years - 80 Years	Inmune Bio, Inc.
Study to Assess the Efficacy of XPro1595 in Patients With Mild Cognitive Impairment With Biomarkers of Inflammation	NCT05321498	Mild Cognitive ... Alzheimer Disea... Dementia Brain Diseases Central Nervous... Nervous System ... Tauopathies Neurodegenerati... Mental Disorder...	XPro1595 Placebo	55 Years - 80 Years	Inmune Bio, Inc.

Spots Global Cancer Trial Database for tumor necrosis factor (tnf)