Digestive System Diseases

All Conditions

Symptoms and General Pathology

Crohn Disease

Necrosis

Intestinal Diseases

Inflammatory Bowel Diseases

Gastroenteritis

Gastrointestinal Diseases

Dermatologic Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Antirheumatic Agents

Antineoplastic Agents

Ustekinumab

Adalimumab

Interleukin-12

Tumor Necrosis Factor Inhibitors

Participants will receive JNJ-64304500 Dose 1 or matching placebo subcutaneous (SC) injection as induction dose (Week 0) followed by JNJ-64304500 Dose 2 or matching placebo SC injection from Week 2 through Week 10 as maintenance dose in addition to adalimumab or its biosimilar as SOC therapy.

Participants will receive JNJ-64304500 Dose 1 or matching placebo SC injection as induction dose (Week 0) followed by JNJ-64304500 Dose 2 or matching placebo SC injection from Week 2 through Week 10 as maintenance dose in addition to ustekinumab as SOC therapy.

JNJ-64304500 will be administered as SC injection.

JNJ-64304500

Matching placebo will be administered as SC injection.

Placebo

Adalimumab will be administered as SOC biological therapy.

Ustekinumab will be administered as SOC biological therapy.

Janssen Research & Development, LLC Clinical Trial

The purpose of this study is to evaluate the efficacy and safety of JNJ-64304500 as add-on therapy to standard of care (SOC) biologic treatment with anti-tumor necrosis factor alpha or anti-interleukin 12/23 inhibitors in participants with active Crohn's disease in response but not remission to SOC biologic therapy.

Biologic agents such as anti-tumor necrosis factor (TNF) and interleukin (IL)-12/23 antagonists have become the standard of care (SOC) in the treatment of patients with Crohn's disease. However, many patients fail to fully respond to treatment. This study will evaluate the efficacy of 10 week add on treatment with JNJ-64304500, compared to placebo, in patients taking SOC anti-TNF or anti-IL12/23 biologics. The study consists of a screening phase (up to 8 weeks); treatment phase (up to 12 weeks and follow-up phase (up to 16 weeks after the last administration of study agent). The total study duration will be up to 34 weeks. Key safety assessments include adverse events, clinical laboratory tests (hematology and chemistry), vital signs, monitoring for injection-site and hypersensitivity reactions, and early detection of active tuberculosis.

A Study of JNJ-64304500 as Add-on Therapy in Participants With Active Crohn's Disease

A Phase 2a Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter, Proof-of-Concept Clinical Study to Evaluate the Safety and Efficacy of JNJ-64304500 as Add-on Therapy to Standard of Care Biologic Therapy With Anti-Tumor Necrosis Factor Alpha or Anti-Interleukin 12/23 in Responder Not Remitter Participants With Active Crohn's Disease

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

An AE can be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non investigational) product, whether or not related to that medicinal (investigational or non investigational) product. TEAEs are AEs with onset during the intervention phase or that are a consequence of a preexisting condition that has worsened since baseline.

TEAEs are AEs with onset during the intervention phase or that are a consequence of a preexisting condition that has worsened since baseline. A SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a suspected transmission of any infectious agent via a medicinal product; is medically important.

Number of participants with TEAEs by system organ class with a frequency threshold of 5 % or more will be reported.

Number of participants with infections, serious infections and infections requiring antimicrobial treatment will be reported.

Number of participants with clinically significant abnormalities in vital signs will be reported.

Number of participants with clinically significant abnormalities in laboratory tests will be reported.

Number of participants with AEs leading to treatment discontinuation will be reported.

Change from baseline in the CDAI score at Week 12 will be reported. CDAI will be assessed by collecting information on 7 different Crohn's disease-related variables (extra-intestinal manifestations, abdominal mass, weight, hematocrit, total number of liquid or very soft stools, abdominal pain/cramping and general well-being) with scores ranging from 0 to approximately 600. The last 4 variables are scored over 7 days by the participant in a diary. A decrease in CDAI over time indicates improvement in disease activity.

Percentage of participants achieving a clinical response as measured by CDAI score (including greater than or equal to \[\>=\] 50, \>=70, \>=100, and \>=150 point reduction from baseline in CDAI) will be reported.

Percentage of participants achieving a clinical remission as measured by CDAI score (CDAI less than \[\<\] 150) will be reported.

Change from baseline in the SES-CD score at Week 12 will be reported. The SES-CD score is based on the evaluation of 4 endoscopic components (presence/size of ulcers, proportion of mucosal surface covered by ulcers, proportion of mucosal surface affected by any other lesions, and presence/type of narrowing/strictures) across 5 ileocolonic segments. Each endoscopic component is scored from 0 to 3 for each segment, and a total score is derived from the sum of all the component scores (range, 0 to 56).

Percentage of participants achieving an endoscopic response defined as at least a 50% improvement from baseline in the SES-CD.

Percentage of participants achieving an endoscopic remission defined as an SES-CD score less than or equal to (\<=) 2.

Change in AP from baseline based on a 0 to 10 numerical rating scale (NRS) will be reported. A score of 0 represents "no abdominal pain" and a score of 10 represents the "worst possible AP," with greater scores indicating greater pain severity and intensity.

Percentage of participants achieving a PRO-2 remission defined as AP mean daily score (AP component of the CDAI score) at or below 1 and stool frequency (SF) mean daily score at or below 3, that is, AP \<=1 and SF \<=3.

Serum concentrations of JNJ-64304500 will be reported.

Antibody titers binding to JNJ-64304500 in positive samples will be reported.

Number of participants receiving at least one dose of JNJ-64304500 with neutralizing antibodies to JNJ-64304500 will be summarized.

Change in PD biomarker levels of CRP from baseline compared with placebo will be reported.

Change in PD biomarker levels of fecal calprotectin from baseline compared with placebo will be reported.

Change in PD biomarker levels of fecal lactoferrin from baseline compared with placebo will be reported.

Janssen Research & Development, LLC

Gastrointestinal Agents

Antibodies

Vedolizumab

Immunoglobulins

Patients presenting an active crohn's disease (HBI score ≥ 4) with an indication of treatment by ustekinumab because of failure or unacceptable side effects of previous treatments, and who have already been treated by at least one anti TNF The patients must be 18 years old or older.

The clinical response is defined as a decrease in the Crohn's Disease Activity Index (CDAI) score ≥ 100 points or a decrease in the HBI score ≥ 3 points.

Evaluation of biological predictive factors of clinical response to ustekinumab

Ustekinumab is a fully human Immune Globulin Gk (IgGk) monoclonal antibody against the common p40 subunit of interleukin-12 and interleukin-23, which are implicated in the pathogenesis of inflammatory bowel disease. Its efficiency to induce and maintain clinical response in patients with anti TNF resistant Crohn's disease has been proved in several clinical trials, and the profile of safety of this treatment was good, but the investigators have few data about biological characteristics of patients treated by Ustekinumab, particularly about ustekinumab through levels and rate of patients developing anti ustekinumab antibodies during the induction and maintenance stages, and no predictive factors of clinical response have been identified yet.

The aim of this study will be to assess the evolution of biological markers of inflammation and ustekinumab trough levels and antibodies, in responders and non responders patients treated by ustekinumab, in order to identify predictive factors of clinical response.

The investigators will perform a prospective observational study, including the patients followed in the University hospital center of Lyon and treated by ustekinumab for a moderate to severe Crohn's disease (with a HBI score≥4 ). All the patients included will have been previously treated by at least one anti TNF and/or Vedolizumab, with specified criteria for a primary non response, a secondary loss of response or unacceptable side effects.

Then, clinical and biological data will be collected for each patient at the inclusion, and then at weeks 4, 8, 16, 24: HBI score, sides effects, extra intestinal manifestations, steroids withdraw, CRP, calprotectin, ustekinumab trough levels and ustekinumab antibodies.

The investigators will compare responding and non responding patients at week 16 (end of the induction period) according to these data.

The hypothesis the investigators state is that an early and significant decrease of the inflammation markers in blood and stools associated with a high ustekinumab through level in blood is associated with a clinical response at week 16 in the patients treated by ustekinumab

Three blood samples of 4 ml, one stool sample of 50 mg

Predictive Factors of Clinical Response to Ustekinumab in Active Crohn's Disease

Identification of Biological Predictive Factors of Clinical Response to Ustekinumab in Patients With Anti-Tumor Necrosis Factor (TNF) Antagonists Refractory Crohn's Disease: Interest of Dosage of C Reactive Protein (CRP), Calprotectin, Ustekinumab Through Levels and Antibodies

Dosage of ustekinumab through level and ustekinumab antibodies: one 4ml blood sample

-Inflammation markers are evaluated : Dosage of CRP and leucocytes in blood: two 4ml blood sample

-Inflammation markers are evaluated : Dosage of calprotectin in stools: one about 50 mg stools sample

Clinical evaluation is realized by a medical visit with physical examination

Clinical evaluation is realized by a medical visit with evaluation of:

* the efficiency of the treatment: evaluation of well being, abdominal pain, stools numbers per day, presence or not of peri anal lesion, arthralgia, fever
* the tolerance/potential side effects of the treatment: infections, headache, skin rash, nausea, allergic reaction, or any clinical manifestation that could be imputed to the treatment

Hospices Civils de Lyon

Immune System Diseases

Blood and Lymph Conditions

Rare Diseases

Graft vs Host Disease

Hematologic Diseases

Homologous Wasting Disease

Acute Graft Versus Host Disease

Immunoglobulin G

Immunoglobulins, Intravenous

Immunologic Factors

Adjuvants, Immunologic

Angiogenesis Inhibitors

Growth Inhibitors

Between 4 and 72 hours prior to start of HCT conditioning therapy, patients receive ustekinumab IV. Beginning 8 weeks after receiving IV ustekinumab, patients receive ustekinumab SC on days 50 (+/- 5 days), 100 (+/- 7 days), and 160 (+/- 7 days) post-HCT in the absence of grade III-IV acute GVHD, disease relapse or unacceptable toxicity. NOTE: HCT infusion takes place on day 0.

Between 4 and 72 hours prior to start of HCT conditioning therapy, patients receive a placebo IV. Beginning 8 weeks after IV placebo, patients receive a placebo SC on days 50 (+/- 5 days), 100 (+/- 7 days), and 160 (+/- 7 days) post-HCT in the absence of grade III-IV acute GVHD, disease relapse, or unacceptable toxicity. NOTE: HCT infusion takes place on day 0.

Placebo Administration

Quality-of-Life Assessment

Questionnaire Administration

Stephanie J. Lee

Ryotaro Nakamoto

Joseph Pidala

This phase II trial studies how well ustekinumab works in preventing acute graft-versus-host disease after unrelated donor hematopoietic cell transplant. Sometimes the transplanted cells from a donor can attack the body's normal tissues (called graft-versus-host disease). Giving ustekinumab after the transplant may help prevent acute graft-versus-host disease by controlling the body's immune response. Funding Source- FDA OOPD.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Between 4 and 72 hours prior to start of HCT conditioning therapy, patients receive ustekinumab intravenously (IV). Beginning 8 weeks after receiving IV ustekinumab, patients receive ustekinumab subcutaneously (SC) on days 50 (+/- 5 days), 100 (+/- 7 days), and 160 (+/- 7 days) post-HCT in the absence of grade III-IV acute GVHD, disease relapse or unacceptable toxicity. NOTE: HCT infusion takes place on day 0.

ARM II: Between 4 and 72 hours prior to start of HCT conditioning therapy, patients receive a placebo IV. Beginning 8 weeks after IV placebo, patients receive a placebo SC on days 50 (+/- 5 days), 100 (+/- 7 days), and 160 (+/- 7 days) post-HCT in the absence grade III-IV acute GVHD, of disease relapse, or unacceptable toxicity. NOTE: HCT infusion takes place on day 0.

After completion of study, patients are followed up at 6, 9, 12, 18, and 24 months post-HCT.

Ustekinumab for the Prevention of Acute Graft-versus-Host Disease After Unrelated Donor Hematopoietic Cell Transplant

Randomized, Placebo-Controlled, Phase II Trial Examining Ustekinumab for Prevention of Graft Vs. Host Disease After Allogeneic Hematopoietic Cell Transplantation

Will be treated as a binary outcome, and the Cochran-Mantel-Haenszel test will be used to compare the two groups based on the stratification factors.

Minnesota risk criteria will be used to assess organ involvement, individual organ staging, and overall acute GVHD grade. Risk classification will be performed per MacMillan et al.

Will be assessed at serial study visits, and scored according to National Institutes of Health Consensus criteria.

Relapse is defined as hematologic relapse or any unplanned intervention (including withdrawal of immune suppression) to prevent progression of disease in patients with evidence (molecular, cytogenetic, flow cytometric, radiographic) of malignant disease. Will be compared using either the log-rank test (if no competing risks) or Gray's test (if competing risks are present). For time-to-event endpoints with competing risks, the log-rank test will also be used for exploratory purposes.

Non-relapse mortality indicates death with primary malignancy that served as HCT indication in remission. Will be compared using either the log-rank test (if no competing risks) or Gray's test (if competing risks are present). For time-to-event endpoints with competing risks, the log-rank test will also be used for exploratory purposes.

Will be compared using either the log-rank test (if no competing risks) or Gray's test (if competing risks are present). For time-to-event endpoints with competing risks, the log-rank test will also be used for exploratory purposes.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of JNJ-64304500 as Add-on Therapy in Participants With Active Crohn's Disease	NCT04655807	Crohn Disease	JNJ-64304500 Placebo Adalimumab Ustekinumab	18 Years - 65 Years	Janssen Research & Development, LLC
Predictive Factors of Clinical Response to Ustekinumab in Active Crohn's Disease	NCT03351647	Crohn Disease	Evaluation of b...	18 Years - 18 Years	Hospices Civils de Lyon
Ustekinumab for the Prevention of Acute Graft-versus-Host Disease After Unrelated Donor Hematopoietic Cell Transplant	NCT04572815	Hematologic and... Hematopoietic a...	Placebo Adminis... Quality-of-Life... Questionnaire A... Ustekinumab	18 Years - 70 Years	Fred Hutchinson Cancer Center

Spots Global Cancer Trial Database for ustekinumab

Every month we try and update this database with for ustekinumab cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for ustekinumab

Every month we try and update this database with for ustekinumab cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for ustekinumab cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.