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A multicenter study to evaluate the effectiveness of budesonide enema foam treatment and the usefulness of
serum biomarker measurement for active ulcerative colitis (BF-LRG)

Evaluation of biomarkers in BF treatment (BF-LRG)

8

The sex of the subjects enrolled in the study was 3/8 male and 5/8 female. The mean plus/minus standard deviation of age at the time of consent was 41.5 plus/minus 11.6 years, height and weight were 163.88 6.50 cm and 56.45 plus/minus 12.22 kg, respectively. Only one subject had a history of smoking, and none of the subjects had comorbidities. The most common type of UC was proctitis 5/8, followed by left-sided colitis 2/8 and total colitis 1/8. 5/8 of the study subjects had recurrent UC and 3/8 had first-episode UC, and all 8 patients had been treated with UC medications.

Number of consents obtained: 12 (first subject first visit: 25 November 2021) Number of patients enrolled who met selection criteria and no exclusion criteria : 8 Number of patients whose follow-up was completed as planned: 8 Cases discontinued : 0 The target number of cases was set at 20, but only 8 cases were enrolled during the enrolment period and the target number could not be achieved.

No adverse events, including deaths, serious adverse events or events leading to discontinuation, were reported during the study.

Primary endpoint: Proportion of active cases and pre/post comparison of LRG scores In this study, cases that achieved a Mayo score of MES (median) = 0 or 1, blood stool score = 0 and bowel frequency score = 1 or less at 6 weeks were considered valid cases and LRG measurements and LRG change rates at 0 and 6 weeks were evaluated. In the PPS, 4/8 (50.0%) patients were valid cases and 4/8 (50.0%) were invalid cases. LRG measurements (mean plus/minus standard deviation) for active cases were 10.95 plus/minus 2.44 maicrog/mL at week 0 and 8.70 plus/minus 1.24 maicrog/mL at 6 weeks or discontinuation, with no statistically significant difference (p = 0.1250). LRG measurements at 0 and 6 weeks were higher in inactive patients than in active patients, but there was no statistically significant difference (p = 0.1250).The change in LRG was -18.79 plus/minus 14.03% in active patients and -28.44 plus/minus 15.29% in inactive patients. The change was greater in the inactive patients, but there was no statistically significant difference between the active and inactive patients (p = 0.3429). Secondary endpoints: degree of remission according to Mayo Score and measured biomarkers (LRG and CRP) and percent change to achieve remission. In the PPS,UC remission rates at 6 weeks by Mayo score were 0/8 for CMH, 4/8 for MH, and 7/8 for CR, with CMH not achieved. In fact, MH was achieved in IWAT-01, IWAT-02, IWAT-03 and TUJI-03 and CR was observed in all cases except OMOR-01. Statistically significant differences in pre- and post-treatment biomarker measurements (LRG/CRP) were observed only for LRG measurements in patients with CR, with mean standard deviations plus/minus 14.04 plus/minus 5.54 maicrog/mL at week 0 and 10.54 plus/minus 2.68 maicrog/mL at week 6 or discontinuation (p = 0.0156). In addition, the rate of change of the biomarkers before and after treatment was compared according to the degree of remission and no statistically significant difference was observed for either LRG or CRP.

The study had fewer subjects as the target number of cases was not reached. The smaller than expected difference in LRG measurements between effective and ineffective cases made it difficult to draw firm conclusions about the efficacy and safety of the study drug. However, LRG or combined LRG and CRP measurements may be accurate indicators for predicting MH and CR. Several cytokines also correlated with these biomarkers, suggesting that further case accumulation is needed.

Sept. 30, 2024

No

None

https://jrct.mhlw.go.jp/latest-detail/jRCTs031210326

Matsuoka Katsuyoshi

Toho University Sakura Medical Center

564-1Shimoshizu,Sakura,Chiba

katsuyoshi.matsuoka@med.toho-u.ac.jp

Matsuoka Katsuyoshi

Toho University Sakura Medical Center

564-1Shimoshizu,Sakura,Chiba

+81-43-462-8811

katsuyoshi.matsuoka@med.toho-u.ac.jp

Complete

Sept. 21, 2021

Interventional

single arm study

open(masking not used)

no treatment control/standard of care control

single assignment

treatment purpose

Include patients with mild to moderate UC who meet all the following 1 to 6.
1. Patients diagnosed with UC according to the ulcerative colitis/Crohn's disease diagnostic criteria and treatment guidelines (revised in 2019)
2. Patients whose total Mayo score evaluated on the eligibility confirmation date was 10 points or less and each sub-score met the following.
(1) Patients with MES >_ 2 at the most active site from the rectum to the sigmoid colon and <_ 1 at the proximal site beyond the sigmoid colon on colonoscopy performed on the eligibility confirmation date.
(2) Patients with a physician's general assessment score of 1-2 on the eligibility confirmation date.
3. Gender: Not specified.
4. Age: 16 years or older (at the time of acquisition of Consent)
5. Visit classification: Outpatient
6. Patients who can obtain written consent (however, if the patient is under 20 years old, obtain written consent from the substitute)

1.Patients who received the following pharmacotherapy or treatment within the period of time as shown below:
[Two weeks before the start date of study drug administration]
New addition of mesalazine preparation (enema / suppository) and salazosulfapyridine preparation (suppository)
Antidiarrheal drug
Bowel cleaning composition (Except used for pre-preparation of colonoscopy in this clinical study)
Laxatives (Except used for pre-preparation of colonoscopy in this clinical study)
Enema (Except used for pre-preparation of colonoscopy in this clinical study)
[Four weeks before the start date of study drug administration]
If the dose of Mesalazine formulations is over then 4.0 g/day (excluding Asacol tablets and Rialda tablets)
If the dose of Asacol tablets is over then 3.6 g/day
If the dose of Rialda tablets is over then 4.8 g/day.
If the dose of Salazosulfapyridine formulation is over then 8.0 g/day
Leukocytapheresis
Antibiotics or antibacterial drugs for the treatment of UC.
Live vaccines
[Eight weeks before the start date of study drug administration]
Corticosteroid formulations (oral, enema, suppositories, hemorrhoid treatment, inhalants, injections)
[Twelve weeks before the start date of study drug administration]
Immunomodulators(cyclosporine, tacrolimus, methotrexate, azathioprine,6-mercaptopurine)
Antibody preparation (anti-TNFa antibody agents, vedolizumab, ustekinumab)
JFK inhibitors (tofacitinib)
2. Patients who have changed the dosage or administration of the following drug therapies within the following period:
[One weeks before the start date of study drug administration]
Probiotics
[Two weeks before the start date of study drug administration]
Mesalazine preparation (enema / suppository), salazosulfapyridine preparation (suppository)
[Four weeks before the start date of study drug administration]
Mesalazine formulations (oral), salazosulfapyridine formulation preparation (oral)
3. Patients with a history of resection of the sigmoid colon or rectum (excluding polypectomy), or patients scheduled for surgical treatment of the gastrointestinal tract during the study period.
4. Patients who are suspected clinically to have infectious enteritis.
5. Patients with infectious diseases and deep mycoses for which there is no effective antibacterial agent.
6. Patients with serious heart disease, nephropathy, or hepatic disorder
7. Patients with (or suspected to diagnosed with) malignant tumor
8. Female patients who are pregnant, lactating, or who may be pregnant
9. Patients who wish to become pregnant during the administration period of this study drug, or female patients who do not agree with using any appropriate medical methods for contraception (concomitant use of intrauterine devices, pessaries, or partner condoms, etc. However, the use of oral contraceptives is excluded).
10. Patients with a history of allergic reaction to budesonide
11. Patients who are receiving desmopressin acetate hydrate
12. Patients who participated in other clinical trials within 12 weeks prior to any examination or observation specified in this study protocol
13. Other patients who are judged to be inappropriate for this study by the principal investigator, etc.

Both

Ulcerative colitis

Budesonide foam was administered as a study drug

Ulcerative colitis

Budesonide

Response rate of the study drug (ratio of patients with response*1 among the enrolled patients) and before-and-after comparison of LRG values at 0 and 6 weeks in patients with response (paired median test will be performed)
*1 Response is defined by MES of 0 or 1, the rectal bleeding sub-score of 0, and stool frequency sub-score of 1 or less at week 6.
*2: MES is evaluated by the Endoscopic Score Evaluation Committee.

1. Percentage changes in biomarkers (serum LRG and serum CRP) values between baseline and Week 6 in patients stratified by achievement of remission (CMH/MH/CR). The Weilcoxon signed-rank test will be implemented.
2. The cut off value were calculated by ROC analysis of each biomarker (serum LRG and serum CRP) in patients stratified by achievement of remission (CMH / MH / CR)
3. Correlation between the efficacy of the study drug and inflammation type
4. Correlation between each sub-score of the Mayo score * 1 and biomarker (serum LRG and serum CRP) values
5. Correlation between serum LRG and serum CRP with inflammation type evaluated by cytokine expr
ession level (mRNA levels)
6. Histological evaluation of colonic mucosa by the Histological Evaluation Committee (evaluated by the Geboes Index, the Nancy Index, the Robert Histological Index)
* 1 MES is evaluated by the Endoscopic Score Evaluation Committee.

+81-3-3470-3360

June. 21, 2021

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