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Effects of adrenomedullin in biologics-resistant patients with Crohn disease: randomized, double-blind, placebo-controlled phase 2a clinical trial

Phase 2a clinical trial for Crohn disease using adrenomedullin

24

Eligible subjects were patients aged 18 to 75 years, who had a definitive diagnosis of CD and were receiving maintenance therapy with the same biologics for at least 3 months, without adequate response to the therapy (200 < Crohn's disease activity index [CDAI] < 450).

All 24 patients completed the 7 days of administration of the test drug. Of the 24 patients, 22 patients completed the 8-week follow-up period. one patient (high-dose AM [15 ng/kg/min] group) quit the study before 8 weeks due to low improvement. Another patient (high-dose AM group) quit the study at 8 weeks due to SAE associated with the endoscopic examination, but CDAI was obtained before SAE.

Any adverse effects were obserbed in 4 patients (50%) with placebo group, 7 patients (88%) with middle dose of AM group, and 8 patients (100%) with high dose AM group. Symptoms related to the vasodilatory effect of AM, such as headaches, palpitations, and flushes, were more frequently observed in the AM-treated groups than in the placebo group. SAE, namely bacteremia, occurred after an endoscopic examination which was conducted after the 7-day AM administration in the high-dose AM group. We considered that this SAE was not related to AM administration.

No differences in the primary endpoints were observed between the three groups by the 8th week.

No differences in the secondary endpoints were observed between the three groups by the 8th week.A significant difference in CDAI was observed between the placebo and adrenomedullin-treated groups at 24 weeks (P = 0.043) in the mixed-effects model.

In this trial, we observed a long-lasting (24 weeks) decrease in CDAI in the adrenomedullin-treated groups. Adrenomedullin might be beneficial for biologic-resistant CD, but further research is needed.

July. 15, 2022

https://doi.org/10.1111/jgh.15945

No

Faculty of Medicine, University of Miyazaki

5200 Kihara, Miyazaki, Miyazaki 889-1692, Japan

toshihiro_kita@med.miyazaki-u.ac.jp

Faculty of Medicine, University of Miyazaki

Toshihiro Kita

+81-985-85-0872

toshihiro_kita@med.miyazaki-u.ac.jp

completed

May. 23, 2018

Interventional

multicenter, randomized, double-blind, placebo-controlled study

treatment purpose

2

Biologics-resistant patients against maintenance therapy of biologics

Non-responder for biologics
Patients with small intestinal lesion and having risk of ileus
Patient with fulminant Crohn disease(CD)
Patient need early operation for CD
Patient with active infection
Patient with severe complication(s)
Patient with malignancy or past history of malignancy
Pregnant woman

Both

Crohn disease

investigational material(s)
Generic name etc : adrenomedullin
INN of investigational material : adrenomedullin
Therapeutic category code : 249 Other hormone preparations (including antihormone preparations)
Dosage and Administration for Investigational material : 8 hours infusion per day

control material(s)
Generic name etc : placebo
INN of investigational material : placebo
Therapeutic category code : --- Other
Dosage and Administration for Investigational material : 8 hours infusion per day

efficacy
change of CDAI at week 8

safety
efficacy
change of CDAIat week 4 and 6
effective rate of CDAI at week 8
endoscopic evaluation (SESCD) at week 8
change of CRP at week 4 and 8
fecal immunochemical test and calprotectin at week 1

+81-985-85-9852

Mar. 01, 2018