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JOURNAL ONKOLOGIE – STUDIE

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

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NCT-Nummer:
NCT04655807

Studienbeginn:
Januar 2021

Letztes Update:
20.01.2021

Wirkstoff:
JNJ-64304500, Placebo, Adalimumab, Ustekinumab

Indikation (Clinical Trials):
Crohn Disease

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Janssen Research & Development, LLC

Collaborator:
-

Studienleiter

Janssen Research & Development, LLC Clinical Trial
Study Director
Janssen Research & Development, LLC

Kontakt

Studienlocations (3 von 54)

Darmzentrum Klinikum Augsburg
Stenglinstraße 2
86156 Augsburg
Deutschland» Google-Maps
Universitätsklinikum Frankfurt/ Medizinische Klinik 1
60590 Frankfurt
(Hessen)
Germany» Google-Maps
Zentrum für Gastroenterologie Saar MVZ GmbH
66111 Saarbrücken
(Saarland)
Germany» Google-Maps
Universitaetsklinik Tuebingen
72076 Tübingen
(Baden-Württemberg)
Germany» Google-Maps
Universitätsklinikum Ulm, Klinik für Innere Medizin II
89081 Ulm
(Baden-Württemberg)
Germany» Google-Maps
University of California, San Francisco
94115 San Francisco
United States» Google-Maps
Medical Research Center of Connecticut
06518 Hamden
United States» Google-Maps
Medisphere Medical Research Center, Llc
47714 Evansville
United States» Google-Maps
Vanderbilt University Medical Center
37212 Nashville
United States» Google-Maps
Gastroenterology Associates of Central Virginia
24502 Lynchburg
United States» Google-Maps
Toronto Immune & Digestive Health Institute Inc.
M6A 3B4 Toronto
Canada» Google-Maps
CHU Saint-Etienne - Hôpital Nord
42270 Saint-Priest en Jarez
France» Google-Maps
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
20122 Milano
Italy» Google-Maps
Ospedale Classificato Equiparato Sacro Cuore Don Calabria di Negrar
37024 Negrar ( Ve)
Italy» Google-Maps
Casa Sollievo della Sofferenza, IRCCS
71013 San Giovanni Rotondo
Italy» Google-Maps
National Center for Global Health and Medicine
162-8655 Tokyo
Japan» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed Description:

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.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Have confirmed clinical diagnosis of Crohn's disease or fistulizing Crohn's disease of

at least 3 months' duration

- Initiated standard of care (SOC) biologic therapy for at least 12 uninterrupted weeks

(including the induction dose) prior to Week 0 and agree to continue to maintain their

SOC biologic with no change in dose level or interruption for the duration of the

study. Adalimumab (including HUMIRA or an equivalent biosimilar which could include:

HULIO, HYRIMOZ, IMRALDI, or AMGEVITA) at maintenance dose of 40 milligram (mg)

subcutaneous (SC) every 2 weeks (q2w) plus minus (+ -) 4 days or Ustekinumab at

maintenance dose of 90 mg SC every 8 weeks (q8w) + - 7 days

- Have active Crohn's disease (CD), with a baseline crohn's disease activity index

(CDAI) score of greater than or equal to (>=) 180 but less than or equal to (<=) 400

- Participant with a family history of colorectal cancer, personal history of increased

colorectal cancer risk, age greater than (>) 50 years, or other known risk factor must

be up-to-date on colorectal cancer surveillance

- Participant who has had extensive colitis for >=8 years, or disease limited to the

left side of the colon for >=12 years, must either have had a colonoscopy to assess

for the presence of dysplasia within 1 year before the first administration of study

agent or a colonoscopy to assess for the presence of malignancy at the screening

visit, with no evidence of malignancy

- A woman of childbearing potential must have a negative highly sensitive serum (beta-

human chorionic gonadotropin [beta-hCG]) pregnancy test result at screening and a

negative urine pregnancy test result at Week 0 and throughout the study

Exclusion Criteria:

- Has complications of Crohn's disease as defined in study protocol

- Currently has or is suspected to have an abscess

- Concomitant or previous medical therapies received: has previously demonstrated

suboptimal response, loss of response, or intolerance to more than 2 approved advanced

therapies

- Concomitant or previous medical therapies received: corticosteroids and

5-aminosalicylic acid (5-ASA) compounds at unstable or above recommended doses are not

permitted. Individuals receiving stable doses (oral corticosteroids at a

prednisone-equivalent dose at or below 20 mg/day, or 6 mg/day of budesonide, 2.5

mg/day beclomethasone dipropionate, or at or below 5-ASA doses of 1.5 gram (g)/day) or

if individuals have been discontinued, for at least 2 weeks before start of first

study intervention (Week 0), are permitted

- Concomitant or previous medical therapies received: has received any of the following

prescribed medications or therapies within the specified period or has plans to

initiate throughout the study: conventional immunomodulators (that is , azathioprine

[AZA], 6-mercaptopurine [6 MP], or methotrexate [MTX]) within 4 weeks of first dose of

study intervention; oral immunomodulatory agents (example, 6-thioguanine [6-TG],

cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil, tofacitinib and other

Janus kinase [JAK] inhibitors [including investigational JAK inhibitors]) less than

(<) 6 weeks or within 5 half-lives of agent before first dose of SOC biologic,

whichever is longer; all other immunomodulatory biologic agents (including

investigational biologics) received within 12 weeks or within 5 half-lives of first

dose of SOC biologic, whichever is longer

- Infections or predisposition to infections criteria: has a stool culture or other

examination positive for an enteric pathogen, including clostridium difficile toxin,

in the last 4 months unless a repeat examination is negative and there are no signs of

ongoing infection with that pathogen

- Has a transplanted organ (with exception of a corneal transplant that needs to have

occurred > 12 weeks before screening)

Studien-Rationale

Primary outcome:

1. Number of Participants with Adverse Events (AEs) and Treatment Emergent Adverse Events (TEAEs) (Time Frame - Up to Week 26):
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.

2. Number of Participants with Treatment-emergent Serious Adverse Events (SAEs) (Time Frame - Up to Week 26):
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.

3. Number of Participants with TEAEs by System Organ Class with a Frequency Threshold of 5 Percent (%) or More (Time Frame - Up to Week 26):
Number of participants with TEAEs by system organ class with a frequency threshold of 5 % or more will be reported.

4. Number of Participants with Infections, Serious Infections and Infections Requiring Antimicrobial Treatment (Time Frame - Up to Week 26):
Number of participants with infections, serious infections and infections requiring antimicrobial treatment will be reported.

5. Number of Participants with Clinically Significant Abnormalities in Vital Signs (Time Frame - Up to Week 26):
Number of participants with clinically significant abnormalities in vital signs will be reported.

6. Number of Participants with Clinically Significant Abnormalities in Laboratory Tests (Time Frame - Up to Week 26):
Number of participants with clinically significant abnormalities in laboratory tests will be reported.

7. Number of Participants with AEs Leading to Treatment Discontinuation (Time Frame - Up to Week 26):
Number of participants with AEs leading to treatment discontinuation will be reported.

8. Change from Baseline in the Crohn's Disease Activity Index (CDAI) Score at Week 12 (Time Frame - Baseline and Week 12):
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.

Secondary outcome:

1. Percentage of Participants Achieving Clinical Response (Time Frame - Week 12):
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.

2. Percentage of Participants Achieving Clinical Remission (Time Frame - Week 12):
Percentage of participants achieving a clinical remission as measured by CDAI score (CDAI less than [<] 150) will be reported.

3. Change from Baseline in the Simple Endoscopic Score for Crohn's disease (SES-CD) at Week 12 (Time Frame - Baseline and Week 12):
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).

4. Percentage of Participants Achieving an Endoscopic Response (Time Frame - Week 12):
Percentage of participants achieving an endoscopic response defined as at least a 50% improvement from baseline in the SES-CD.

5. Percentage of Participants Achieving an Endoscopic Remission (Time Frame - Week 12):
Percentage of participants achieving an endoscopic remission defined as an SES-CD score less than or equal to (<=) 2.

6. Change From Baseline in Abdominal Pain (AP) (Time Frame - Baseline up to Week 12):
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.

7. Percentage of Participants Achieving Patient-Reported Outcome (PRO)-2 Remission (Time Frame - Week 12):
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.

8. Serum Concentrations of JNJ-64304500 (Time Frame - Up to Week 26):
Serum concentrations of JNJ-64304500 will be reported.

9. Number of Participants with Antibodies to JNJ-64304500 (Time Frame - Up to Week 26):
Antibody titers binding to JNJ-64304500 in positive samples will be reported.

10. Number of Participants with Neutralizing Antibodies to JNJ-64304500 (Time Frame - Up to Week 26):
Number of participants receiving at least one dose of JNJ-64304500 with neutralizing antibodies to JNJ-64304500 will be summarized.

11. Change in Pharmacodynamics (PD) Biomarker Levels of C-Reactive Protein (CRP) from Baseline Compared with Placebo (Time Frame - Baseline, up to Week 26):
Change in PD biomarker levels of CRP from baseline compared with placebo will be reported.

12. Change in PD Biomarker Levels of Fecal Calprotectin from Baseline Compared with Placebo (Time Frame - Baseline, up to Week 26):
Change in PD biomarker levels of fecal calprotectin from baseline compared with placebo will be reported.

13. Change in PD Biomarker Levels of Fecal Lactoferrin from Baseline Compared with Placebo (Time Frame - Baseline, up to Week 26):
Change in PD biomarker levels of fecal lactoferrin from baseline compared with placebo will be reported.

Studien-Arme

  • Experimental: Group 1- Standard of Care (SOC) Biological Therapy: Adalimumab
    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.
  • Experimental: Group 2: SOC Biological Therapy: Ustekinumab
    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.

Geprüfte Regime

  • JNJ-64304500:
    JNJ-64304500 will be administered as SC injection.
  • Placebo:
    Matching placebo will be administered as SC injection.
  • Adalimumab:
    Adalimumab will be administered as SOC biological therapy.
  • Ustekinumab:
    Ustekinumab will be administered as SOC biological therapy.

Quelle: ClinicalTrials.gov


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