A Study in Patients With Erosive Esophagitis to Investigate Safety, Tolerability, and Healing Rates After 4 Weeks Treatment of X842 or Lansoprazole and Symptom Pattern During Subsequent 4 Weeks Treatment With Lansoprazole

Sponsor

Cinclus Pharma AG (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05055128

Collaborator

Parexel (Industry)

240

Enrollment

Locations

Arms

15.5

Anticipated Duration (Months)

3.6

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will be conducted in patients with erosive esophagitis due to gastro-esophageal reflux disease (GERD) Los Angeles (LA) grades C or D, and in patients with at least partial symptom response but still endoscopically unhealed (LA grades A or B) after 8 weeks history of standard treatment healing course with PPI, designed to support dose selection for Phase 3 and to investigate safety, tolerability, and healing rates after 4 weeks treatment of X842 or Lansoprazole, and symptom pattern during subsequent 4 weeks treatment with Lansoprazole.

Condition or Disease	Intervention/Treatment	Phase
Erosive Esophagitis	Drug: X842 Drug: X842 Dummy Drug: Lansoprazole Drug: Lansoprazole Dummy	Phase 2

Detailed Description

This is a randomized, double-blind, active comparator-controlled study with a parallel-group design including four arms with X842 and one arm with Lansoprazole.

Randomization to one of the treatments with X842 twice daily (BID) 25 mg, 50 mg, 75 mg, 100 mg, or Lansoprazole 30 mg once daily (QD) will be based on a 1:1:1:1:1 scheme.

The duration of each patient's participation in the study, including screening, blind treatment period, and open-label treatment period will be approximately 60 days. The patients will be randomized for 4 weeks of double-blind treatment and will be provided with investigational medicinal product for 35 days.

All patients will have an endoscopic evaluation after 4 weeks of treatment. Following the endoscopic evaluation, all patients will receive subsequent 4 weeks of open-label treatment with Lansoprazole. Repeated symptom evaluation to detect symptom patterns will be assessed during this period.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

240 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Randomized Double-blind, Double Dummy, Active Comparator-controlled Dose-finding Study in Patients With Erosive Esophagitis Due to Gastro-esophageal Reflux Disease (GERD) Los Angeles Grade C or D, and Patients With at Least Partial Symptom Response But Endoscopically Still Unhealed After 8 Weeks History of Standard Treatment Healing Course With Proton-pump Inhibitor (PPI), to Investigate Safety, Tolerability, and Healing Rates After 4 Weeks Treatment of X842 or Lansoprazole, and Symptom Pattern During Subsequent 4 Weeks Treatment With Lansoprazole

Actual Study Start Date :

Aug 16, 2021

Anticipated Primary Completion Date :

Aug 31, 2022

Anticipated Study Completion Date :

Nov 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: X842 25 mg BID Patients will receive 2 tablets (X842 25mg + X842 dummy) and 1 capsule (Lansoprazole dummy) in the morning, and 2 tablets (X842 25 mg + X842 dummy) in the evening during 4-week double-blind treatment. Thereafter, patients will receive 1 capsule of Lansoprazole 30 mg QD for 4 weeks.	Drug: X842 Patients will receive X842 tablets. Drug: X842 Dummy Patients will receive matching placebo tablets for X842. Drug: Lansoprazole Patients will receive Lansoprazole capsule. Drug: Lansoprazole Dummy Patients will receive matching placebo capsules for Lansoprazole.
Experimental: X842 50 mg BID Patients will receive 2 tablets (X842 50 mg + X842 dummy) and 1 capsule (Lansoprazole dummy) in the morning, and 2 tablets (X842 50 mg + X842 dummy) in the evening during 4-week double-blind treatment. Thereafter, patients will receive 1 capsule of Lansoprazole 30 mg QD for 4 weeks.	Drug: X842 Patients will receive X842 tablets. Drug: X842 Dummy Patients will receive matching placebo tablets for X842. Drug: Lansoprazole Patients will receive Lansoprazole capsule. Drug: Lansoprazole Dummy Patients will receive matching placebo capsules for Lansoprazole.
Experimental: X842 75 mg BID Patients will receive 2 tablets (X842 50 mg + X842 25 mg) and 1 capsule (Lansoprazole dummy) in the morning, and 2 tablets (X842 50 mg×2) in the evening during 4-week double-blind treatment. Thereafter, patients will receive 1 capsule of Lansoprazole 30 mg QD for 4 weeks.	Drug: X842 Patients will receive X842 tablets. Drug: Lansoprazole Patients will receive Lansoprazole capsule. Drug: Lansoprazole Dummy Patients will receive matching placebo capsules for Lansoprazole.
Experimental: X842 100 mg BID Patients will receive 2 tablets (X842 50 mg×2) and 1 capsule (Lansoprazole dummy) in the morning, and 2 tablets (X842 50 mg×2) in the evening during 4-week double-blind treatment. Thereafter, patients will receive 1 capsule of Lansoprazole 30 mg QD for 4 weeks.	Drug: X842 Patients will receive X842 tablets. Drug: Lansoprazole Patients will receive Lansoprazole capsule. Drug: Lansoprazole Dummy Patients will receive matching placebo capsules for Lansoprazole.
Active Comparator: Lansoprazole Patients will receive 2 tablets (X842 dummy×2) and 1 capsule (Lansoprazole 30 mg) in the morning, and 2 tablets (X842 dummy×2) in the evening during 4-week double-blind treatment. Thereafter, patients will receive 1 capsule of Lansoprazole 30 mg QD for 4 weeks.	Drug: X842 Dummy Patients will receive matching placebo tablets for X842. Drug: Lansoprazole Patients will receive Lansoprazole capsule.

Outcome Measures

Primary Outcome Measures

Healing rate of erosive esophagitis [Week 4]
To assess the healing rate of erosive esophagitis due to GERD based on endoscopic assessment. Dose selection for X842 (to identify the dose providing the target effect of 85% healing rate) will be supported through assessment of healing of erosive esophagitis after 4 weeks of treatment.

Secondary Outcome Measures

Number of patients with adverse events (AEs) [From Screening (Day -7 to Day 0) until Week 8]
To assess safety and tolerability of the four dose levels of X842 and Lansoprazole, where Lansoprazole will serve as the active comparator.
Percentage of heartburn-free 24-hour days [Weeks 1, 2, 4 and 8]
To evaluate the percentage to heartburn-free 24-hour days based on eDiary (Reflux Symptom Questionnaire electronic Diary: RESQ-eDiary). The reflux related symptom pattern will be evaluated during the initial 4 weeks treatment with four dose levels of X842 and with Lansoprazole, and the symptom pattern during the subsequent additional 4 weeks (Weeks 5-8) open-label treatment with Lansoprazole. Modified RESQ-eDiary is a validated self-reported questionnaire electronic symptom diary. mRESQ-eD has 3 domains [i.e. Heartburn (min-max: 0-10), Other GERD signs/symptoms (min-max: 0-15) and Regurgitations/Reflux (min-max: 0-8)]. It is used to assess the severity and frequency of gastroesophageal reflux disease symptoms. For severity a 6-point and for frequency a 5-point Likert response format is used. RESQ-eD contains 8 items where 5 assess severity (0=Did not have - 5=Severe) and 3 assess frequency (0=Never - 4=Very often) of symptoms (min-max: 0-33). Higher scores mean a worse outcome.
Investigator assessment of symptom [Week 1-8]
Investigator will assess the severity of patients' heartburn, regurgitation and dysphagia in the 7 days prior to the visit. The assessment will include both the severity grade (for severity, items are coded: none, mild, moderate, severe where none represents no complaints, severe represents incapacitating symptoms) and the frequency (for frequency, a 7-graded Likert scale is used, ranges from none of the time to all of the time) of symptoms. Symptoms are scored as follows: none (no complaints), mild (aware of symptom, but easily tolerated), moderate (discomforting symptom, sufficient to cause interference with normal daily activities and/or sleep), severe (incapacitating symptom, with inability to perform normal daily activities and/or sleep).
Change from baseline in Quality of Life in Reflux and Dyspepsia (QOLRAD) score [Baseline, Weeks 1, 2, 4 and 8]
The reflux related symptom pattern will be evaluated during the initial 4 weeks treatment with four dose levels of X842 and with Lansoprazole, and the symptom pattern during the subsequent additional 4 weeks (Weeks 5-8) open-label treatment with Lansoprazole 30 mg QD. The heartburn version of the QOLRAD is a disease specific instrument and contains 25 questions addressing concerns associated with gastrointestinal symptoms. The questions are rated on a seven-grade (1-7) Likert scale, score of 1 represents low quality of life and as higher the score the better is the patient. If 50% or more of the questions in one dimension are completed, the mean value of the completed items should replace the missing responses. The questions are categorized into 5 domains: emotional distress, sleep disturbance, vitality, food/drink problems and physical/social functioning. The score ranges from 1 to 175, higher scores mean a better outcome.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Body mass index (BMI) ≥ 18 and ≤ 40 kg/m^2 at screening.
Gastro-esophageal reflux disease with endoscopically confirmed esophagitis:

LA grade C or D ≤7 days before randomization (with or without historical PPI treatment) or
LA grade A or B ≤7 days before randomization and history of treatment with the standard healing course of PPI for minimum of 8 weeks prior to screening and ≤7 days of non-treatment during this period and at least partial symptom response during the minimum of 8 weeks of PPI treatment.

Willing and able to comply with all aspects of the protocol (including capsule swallowing, diary completion, etc.).
Capable of signing informed consent form.

Exclusion Criteria:

History or presence of any clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disease or disorder.
Patients with so-called "alarm features" in symptomatology, like odynophagia, severe dysphagia, bleeding, weight loss, anemia, and blood in stool pointing to a possible malignant disease of the gastrointestinal (GI) tract.
Present clinically significant psychiatric diagnosis.
History of malignancy of any organ system.
Presence of esophageal ulcer, stricture, Barrett´s esophagus or suspected esophagitis secondary to infection, inflammatory disease, ingestion of erosive chemicals or history of any surgical or medical condition which might significantly alter the Gastro-oesophageal reflux disease (GERD) status or the absorption, distribution, metabolism or excretion of drugs.
Known severe atrophic gastritis.
Any planned major surgery within the duration of the study.
History of a positive result for human immunodeficiency virus (HIV), Hepatitis B surface antigen (HBsAg), antibody to Hepatitis B core antigen (anti-HBcAg), or antibody to Hepatitis C virus (anti-HCV) or presence of these findings on screening.
History of long QTc syndrome (e.g. QTc ≥450 ms for males and ≥470 ms for females).
Cardiac arrhythmias or any clinically significant abnormalities in the resting 12-lead ECG at the time of screening, as judged by the Investigator.
History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity.
Current or history of alcohol, drug abuse and/or use of anabolic steroids within 2 years prior to screening.
Women who are pregnant or breastfeeding.
Patients who have previously participated (completed or withdrawn) in this study CX842A2201.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Omega Research Orlando	DeBary	Florida	United States	32713
2	Genesis Clinical Research - Tampa	Tampa	Florida	United States	33614
3	Revive Research Institute	Farmington Hills	Michigan	United States	48334-3275
4	Onyx Clinical Research, LLC	Flint	Michigan	United States	48532
5	Javara Research	Charlotte	North Carolina	United States	28287
6	3A Research, LLC	El Paso	Texas	United States	79225
7	coastal Carolina Research Center	Houston	Texas	United States	77099
8	Medical Center Excelsior	Sofia	Sofia-Grad	Bulgaria	1233
9	NMTH 'Tsar Boris III'	Sofia	Sofia-Grad	Bulgaria	1233
10	DCC XIV Sofia	Sofia	Sofia-Grad	Bulgaria	1404
11	DCC XIV Sofia	Sofia	Sofia-Grad	Bulgaria	1408
12	Medical Centre Asklepii	Dupnitsa		Bulgaria	2600
13	Medical Center Medconsult Pleven	Pleven		Bulgaria	5800
14	MC Exacta Medical OOD	Pleven		Bulgaria	5809
15	DCC-1 Sliven	Plovdiv		Bulgaria	4002
16	MHAT "Kaspela"	Plovdiv		Bulgaria	4002
17	Medical Center Prolet EOOD	Ruse		Bulgaria	7000
18	Diagnostive Consultative Center-1 Sliven	Sliven		Bulgaria	8800
19	Medical Center Hera - Gastroenterology office	Sliven		Bulgaria	8800
20	2-nd MHAT	Sofia		Bulgaria	1202
21	Medical Center Excelsior	Sofia		Bulgaria	1407
22	MHAT "Sveti Ivan Rilski" - Sofia	Sofia		Bulgaria	1431
23	Medical Center Hera - Gastroenterology office	Sofia		Bulgaria	1510
24	Medical Center New Rehabilitation Center EOOD	Stara Zagora		Bulgaria	6003
25	Medical Center "Biomed 99" Ltd	Vidin		Bulgaria	3700
26	Mhat "Hristo Botev"	Vratsa		Bulgaria	3000
27	Libera Scientia s.r.o.	Praha 3		Czechia	130 00
28	ResTrial GastroEndo s.r.o.	Praha 4		Czechia	143 00
29	LTD"Brothers"	Batumi	Ajaria	Georgia	6010
30	A. Aladashvili clinic LLC	Tbilisi		Georgia	0102
31	LTD Israeli-Georgian Medical Research Clinic "Helsicore"	Tbilisi		Georgia	0112
32	LTD TSMU and Ingorokva High Medical Technology University Clinic	Tbilisi		Georgia	0141
33	Emergency Cardiology Center named by acad. G. Chapidze	Tbilisi		Georgia
34	LTD INNOVA - Gestroenterology	Tbilisi		Georgia
35	Bekes Megyei Kozponti Korhaz, Dr.Rethy Pal Tagkorhaz	Békéscsaba	Békés	Hungary	5600
36	Szegedi Tudomanyegyetem Általános Orvostudományi Kar	Szeged	Csongrád	Hungary	H-6725
37	Bugat Pal Hospital/Clinexpert Gyongyos Ltd.	Gyöngyös	Heves	Hungary	3200
38	Szent Borbala Korhaz	Tatabánya	Komárom-Esztergom	Hungary	2800
39	ClinExpert Kft.	Budapest	Pest	Hungary	1032
40	MH Egészségügyi Központ - Gasztroenterológiai Osztály	Budapest	Pest	Hungary	1062
41	Jávorszky Ödön Kórház	Vac	Pest	Hungary	H-2600
42	Obudai Egeszsegugyi Centrum Kft.	Budapest		Hungary	1036
43	Pannonia Maganorvosi Centrum Kft	Budapest		Hungary	H-1136
44	Centrum Medyczne Melita Medical	Wrocław	Dolnoslaskie	Poland	50-449
45	NZOZ "Centrum Medyczne KERMED"	Bydgoszcz	Kujawsko-pomorskie	Poland	85-681
46	Centrum Diagnostyczno - Lecznicze Barska sp. z o.o. Szpital	Włocławek	Kujawsko-pomorskie	Poland	87-800
47	Szpital Zakonu Bonifratrow Sw. Jana Bozego w Lodzi	Lodz	Lódzkie	Poland	90-302
48	WIP Warsaw IBD Point Profesor Kierkus	Warszawa	Mazowieckie	Poland	04-730
49	Centrum Medyczne Pratia Czestochowa	Częstochowa		Poland	42-200
50	Oswiecimskie Centrum Badan Klinicznych Medicome Sp. z o.o.	Oswiecim		Poland	32-600
51	ETG Skierniewice	Skierniewice		Poland	96-100
52	Twoja Przychodnia - Szczecinskie Centrum Medyczne	Szczecin		Poland	71-270
53	EuroMediCare Szpital Specjalistyczny z Przychodnia	Wrocław		Poland	50-449
54	EuroMediCare Szpital Specjalistyczny z Przychodnia	Wrocław		Poland	54-144
55	ETG Zamosc	Zamość		Poland	22-400
56	Clinical Hospital Centre Dragisa Misovic	Belgrade		Serbia	11000
57	Euromedik	Belgrade		Serbia	11000
58	Zvezdara University Medical Center	Belgrade		Serbia	11000
59	Clinical Hospital Center Bezanijska Kosa	Belgrade		Serbia	11080
60	Clinical Center Kragujevac - Center for Gastroenterohepatology	Kragujevac	Šumadijski Okrug	Serbia	34000
61	Oblasna komunalna ustanova "Chernivetska oblasna klinichna likarnia"	Chernivtsi	Chernivets'ka Oblast'	Ukraine	58001
62	Medical Center "OK Clinic"	Kyiv	Kyïv	Ukraine	2091
63	KNP "Odeska oblasna klinichna likarnia" Odeskoi oblasnoi rady"	Odesa	Odes'ka Oblast'	Ukraine	65025
64	Medychnyi Tsentr TOV "KHELS KLINIK" - viddil Gasrtroenterology, Hepatology and Endocrinology	Vinnytsia	Vinnyts'ka Oblast'	Ukraine	21009
65	Komunalne nekomertsiine pidpryiemstvo "Vinnytska miska klinichna likarnia #1"	Vinnytsia	Vinnyts'ka Oblast'	Ukraine	21029
66	KNP "Zakarpatska oblasna klinichna likarnia imeni Andriia Novaka" Zakarpatskoi oblasnoi rady	Uzhhorod	Zakarpats'ka Oblast'	Ukraine	88018
67	KU "6-A miska klinichna likarnia"	Zaporizhzhia	Zaporiz'ka Oblast'	Ukraine	69035