Clinical trial NCT05055128: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Erosive Esophagitis
Keywords: Lansoprazole
Los Angeles Grade
Double-blind
Active comparator-controlled
Proton-pump inhibitor
Dose selection
Lead sponsor: Cinclus Pharma AG
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2021-09-24
Enrollment: 248
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: Inclusion Criteria:

1. Body mass index (BMI) ≥ 18 and ≤ 40 kg/m\^2 at screening.
2. 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.
3. Willing and able to comply with all aspects of the protocol (including capsule swallowing, diary completion, etc.).
4. Capable of signing informed consent form.

Exclusion Criteria:

1. History or presence of any clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disease or disorder.
2. 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.
3. Present clinically significant psychiatric diagnosis.
4. History of malignancy of any organ system.
5. 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.
6. Known severe atrophic gastritis.
7. Any planned major surgery within the duration of the study.
8. 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.
9. History of long QTc syndrome (e.g. QTc ≥450 ms for males and ≥470 ms for females).
10. Cardiac arrhythmias or any clinically significant abnormalities in the resting 12-lead ECG at the time of screening, as judged by the Investigator.
11. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity.
12. Current or history of alcohol, drug abuse and/or use of anabolic steroids within 2 years prior to screening.
13. Women who are pregnant or breastfeeding.
14. Patients who have previously participated (completed or withdrawn) in this study CX842A2201.

Primary outcomes:
measure: Number of Patients With Esophageal Mucosa Healing
timeFrame: Week 4
Secondary outcomes:
measure: Number of Patients With Adverse Events (AEs)
timeFrame: From Screening (Day -7 to Day 0) until Week 8
measure: Percentage of Heartburn-Free 24-hour Days
timeFrame: Weeks 1 and 8
measure: Percentage at Most-mild Heartburn 24-hour Days
timeFrame: Weeks 1 and 8
measure: Investigator Assessment of Symptoms by Frequency and Severity
timeFrame: Weeks 1 and 8
measure: Change From Baseline in Quality of Life in Reflux and Dyspepsia (QOLRAD) Score
timeFrame: Baseline, Weeks 1, and 8
Other outcomes:
Locations:
city: Tampa
country: United States
facility: Genesis Clinical Research - Tampa
state: Florida
city: Sofia
country: Bulgaria
facility: Medical Center Excelsior
state: Sofia-Grad
city: Sofia
country: Bulgaria
facility: DCC XIV Sofia
state: Sofia-Grad
city: Sofia
country: Bulgaria
facility: DCC XIV Sofia
state: Sofia-Grad
city: Dupnitsa
country: Bulgaria
facility: Medical Centre Asklepii
city: Pleven
country: Bulgaria
facility: Medical Center Medconsult Pleven
city: Plovdiv
country: Bulgaria
facility: DCC-1 Sliven
city: Plovdiv
country: Bulgaria
facility: MHAT "Kaspela"
city: Ruse
country: Bulgaria
facility: Medical Center Prolet EOOD
city: Sliven
country: Bulgaria
facility: Diagnostive Consultative Center-1 Sliven
city: Sliven
country: Bulgaria
facility: Medical Center Hera - Gastroenterology office
city: Sofia
country: Bulgaria
facility: 2-nd MHAT
city: Sofia
country: Bulgaria
facility: Medical Center Excelsior
city: Sofia
country: Bulgaria
facility: MHAT "Sveti Ivan Rilski" - Sofia
city: Sofia
country: Bulgaria
facility: Medical Center Hera - Gastroenterology office
city: Stara Zagora
country: Bulgaria
facility: Medical Center New Rehabilitation Center EOOD
city: Vidin
country: Bulgaria
facility: Medical Center "Biomed 99" Ltd
city: Vratsa
country: Bulgaria
facility: Mhat "Hristo Botev"
city: Praha 4
country: Czechia
facility: ResTrial GastroEndo s.r.o.
city: Batumi
country: Georgia
facility: LTD"Brothers"
state: Ajaria
city: Tbilisi
country: Georgia
facility: A. Aladashvili clinic LLC
city: Tbilisi
country: Georgia
facility: LTD Israeli-Georgian Medical Research Clinic "Helsicore"
city: Tbilisi
country: Georgia
facility: LTD TSMU and Ingorokva High Medical Technology University Clinic
city: Tbilisi
country: Georgia
facility: Emergency Cardiology Center named by acad. G. Chapidze
city: Békéscsaba
country: Hungary
facility: Bekes Megyei Kozponti Korhaz, Dr.Rethy Pal Tagkorhaz
state: Békés
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Általános Orvostudományi Kar
state: Csongrád
city: Budapest
country: Hungary
facility: ClinExpert Kft.
state: Pest
city: Budapest
country: Hungary
facility: Pannonia Maganorvosi Centrum Kft
city: Wrocław
country: Poland
facility: Centrum Medyczne Melita Medical
state: Dolnoslaskie
city: Bydgoszcz
country: Poland
facility: NZOZ "Centrum Medyczne KERMED"
state: Kujawsko-pomorskie
city: Lodz
country: Poland
facility: Szpital Zakonu Bonifratrow Sw. Jana Bozego w Lodzi
state: Lódzkie
city: Oswiecim
country: Poland
facility: Oswiecimskie Centrum Badan Klinicznych Medicome Sp. z o.o.
city: Skierniewice
country: Poland
facility: ETG Skierniewice
city: Szczecin
country: Poland
facility: Twoja Przychodnia - Szczecinskie Centrum Medyczne
city: Wrocław
country: Poland
facility: EuroMediCare Szpital Specjalistyczny z Przychodnia
city: Wrocław
country: Poland
facility: EuroMediCare Szpital Specjalistyczny z Przychodnia
city: Zamość
country: Poland
facility: ETG Zamosc
city: Belgrade
country: Serbia
facility: Zvezdara University Medical Center
city: Chernivtsi
country: Ukraine
facility: Oblasna komunalna ustanova "Chernivetska oblasna klinichna likarnia"
state: Chernivets'ka Oblast'
city: Odesa
country: Ukraine
facility: KNP "Odeska oblasna klinichna likarnia" Odeskoi oblasnoi rady"
state: Odes'ka Oblast'
city: Vinnytsia
country: Ukraine
facility: Medychnyi Tsentr TOV "KHELS KLINIK" - viddil Gasrtroenterology, Hepatology and Endocrinology
state: Vinnyts'ka Oblast'
city: Zaporizhzhia
country: Ukraine
facility: KU "6-A miska klinichna likarnia"
state: Zaporiz'ka Oblast'
Study officials:
References: