Eosinophilic Duodenitis (EoD), Eosinophilic Gastritis (EoG), Eosinophilic Gastroenteritis, Eosinophilic Gastrointestinal Disease (EGID)
Conditions
Keywords
Eosinophilic Gastritis (EoG) with or without Eosinophilic Duodenitis (EoD)
Brief summary
This study is researching an experimental drug called dupilumab. The study is focused on participants with active eosinophilic gastritis (EoG) with or without eosinophilic duodenitis (EoD). Participants with EoD only are not eligible for enrollment. EoG and EoD are uncommon, persistent, allergic/immune diseases in which eosinophils (a type of white blood cell) gather in large numbers in the stomach and small intestine and cause inflammation and damage. The aim of the study is to evaluate the effect of dupilumab on relieving EoG (with or without EoD) symptoms and reducing inflammation in the stomach and, if applicable, small intestine in adults and adolescents aged 12 years and older after at least 24 weeks (about 6 months) and up to 52 weeks (1 year) of treatment. The study is looking at several other research questions, including: * What side effects may happen from taking the study drug * How much study drug is in the blood at different times * Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)
Detailed description
This study has 2 parts and a 12-week (about 3 months) Follow-up Period for all participants * Part A is an open-label treatment period lasting up to 24 weeks (up to 6 months). "Open-label" means that you and the study doctors and the staff staff will know that you are taking the study drug * Part C is an open-label extended treatment period lasting up to 28 weeks (about 7 months). "Extended Treatment Period" means that you will take the study drug for an additional 28 weeks after finishing Part A if you are eligible to take part in this part of the study
Interventions
DRUGDupilumab
Administered as described in the protocol
Sponsors
Regeneron Pharmaceuticals
Sanofi
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Adolescent participants will only be enrolled at study sites in countries/regions as permitted by local regulatory authorities and ethic committees (ECs) 2. Documented endoscopic biopsy supporting a pathologic diagnosis of Eosinophilic gastritis (EoG) at least 3 months prior to screening 3. Screening endoscopic biopsies with a demonstration of eosinophilic infiltration for a diagnosis of EoG, as defined in the protocol 4. Completed at least 11 of 14 days of EoG/EoD-SQ eDiary data entry in the 2 weeks prior to the baseline visit 5. History (by participant report) of at least 2 episodes of EoG (with or without EoD) symptoms per week in 8 weeks before screening, as defined in the protocol 6. An average TSS of ≥ 20 calculated using data collected via the EoG/EoD-SQ eDiary per week for the 2 weeks prior to baseline. An average severity score of ≥4 (on a scale of 0-10) per week for the 2 weeks prior to baseline for at least 2 of the 6 symptoms, as defined in the protocol. Key
Exclusion criteria
1. Body weight less than 40 kg at screening 2. Prior participation in a dupilumab clinical trial, or past or current treatment with dupilumab 3. Helicobacter pylori infection 4. Any esophageal stricture unable to be passed with a standard, diagnostic, upper endoscope or any critical esophageal stricture that requires dilation at screening 5. History of achalasia, Crohn's disease, eosinophilic colitis, ulcerative colitis, celiac disease, and prior gastric or duodenal surgery, as defined in the protocol 6. Other causes of gastric and, if applicable, duodenal eosinophilia or the following conditions: eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) or hyper-eosinophilic syndrome 7. History of bleeding disorders, esophageal or gastric varices that, in the opinion of the investigator, would put the participant at undue risk for significant complications from an endoscopy procedure 8. Initiation or change of a food-elimination diet regimen or re-introduction of a previously eliminated food group in the 4 weeks prior to the screening visit. Participants on a food-elimination diet must remain on the same diet throughout the study 9. Planned or anticipated use of any prohibited medications and procedures during the study 10. Planned or anticipated major surgical procedure during the study 11. Receiving tube feeding or parenteral nutritional at screening NOTE: Other Protocol Defined Inclusion /
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent change in peak gastric eosinophil count eosinophils/high power field (eos/hpf) | Baseline up to 24 Weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in frequency of diarrhea episodes | Baseline up to 52 Weeks | Assessed for only those with diarrhea at baseline |
| Change in frequency of vomiting episodes | Baseline up to 52 Weeks | Assessed for only those with vomiting at baseline |
| Change in the Normalized Enrichment Scores (NES) for the type 2 inflammation transcriptome signature | Baseline up to 52 Weeks | Assessed on gastric tissue Normalized Enrichment Score (NES) reflects the degree to which the activity level of a set of transcripts is overrepresented at the extremes (top or bottom) of the entire ranked list of transcripts within a sample and is normalized by accounting for the number of transcripts in the set. |
| Change in the NES for the type 2 inflammation transcriptome signature | Baseline up to 52 Weeks | Assessed on duodenal tissue from participants with EoD NES reflects the degree to which the activity level of a set of transcripts is overrepresented at the extremes (top or bottom) of the entire ranked list of transcripts within a sample and is normalized by accounting for the number of transcripts in the set. |
| Change in the NES for the EoG disease (EoG diagnostic panel (EGDP]) transcriptome signature | Baseline up to 52 Weeks | Assessed on gastric tissue NES reflects the degree to which the activity level of a set of transcripts is overrepresented at the extremes (top or bottom) of the entire ranked list of transcripts within a sample and is normalized by accounting for the number of transcripts in the set. |
| Proportion of participants who receive rescue medications or procedures | Up to 52 Weeks | — |
| Incidence of treatment-emergent adverse events (TEAEs) | Up to 52 Weeks | A TEAE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. |
| Incidence of treatment-emergent serious adverse events (SAEs) | Up to 52 Weeks | An SAE is any untoward medical occurrence that at any dose: * Results in death - includes all deaths, even those that appear to be completely unrelated to study drug (eg, a car accident in which a patient is a passenger) * Is life-threatening * Requires in-patient hospitalization or prolongation of existing hospitalization * Results in persistent or significant disability/incapacity * Is a congenital anomaly/birth defect * Is an important medical event |
| Incidence of treatment-emergent adverse events of special interest (AESIs) | Up to 52 Weeks | An AESI (serious or non-serious) is one of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the Investigator to the sponsor can be appropriate. Such an event might warrant further investigation in order to characterize and understand it |
| Incidence of TEAEs leading to permanent discontinuation of study treatment | Up to 52 Weeks | A TEAE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. |
| Incidence of anti-drug antibody (ADA) | Up to 52 Weeks | Immunogenicity will be characterized per drug molecule by ADA status |
| Titer of ADA | Up to 52 Weeks | Immunogenicity will be characterized per drug molecule by ADA status |
| Incidence of neutralizing antibody (NAb) to dupilumab | Up to 52 Weeks | Immunogenicity will be characterized per drug molecule by NAb status |
| Concentrations of functional dupilumab in serum at each assessment time point | Baseline up to 64 Weeks | The concentrations of functional dupilumab over time will be summarized by descriptive statistics by study arm for the overall population and for adolescent patients. |
| Proportion of participants achieving a peak gastric eosinophil count of ≤20 eos/hpf | Up to 52 Weeks | — |
| Proportion of participants achieving a peak gastric eosinophil count of ≤30 eos/hpf | Up to 52 Weeks | — |
| Proportion of participants achieving both a peak gastric eosinophil count of ≤20 eos/hpf and a peak duodenal eosinophil count of ≤30 eos/hpf | Up to 52 Weeks | — |
| Proportion of participants achieving a peak duodenal eosinophil count of ≤30 eos/hpf | Up to 52 Weeks | Assessed for only those with duodenal involvement |
| Absolute change in the EoG/EoD-SQ Total Symptom Score (TSS) | Baseline up to 52 Weeks | EoG/EoD-SQ is a PRO collected daily via an eDiary. Symptoms are assessed using an 11-point numerical rating scale (0 through 10). Higher scores indicate a higher symptom burden. Symptom scores are summed on each day with a maximum daily score of 60. The TSS is calculated by averaging daily sum scores over 7 days, with a maximum TSS of 60. |
| Percent change in the EoG/EoD-SQ TSS | Baseline up to 52 Weeks | — |
| Percent change in peak duodenal tissue eosinophil count (eos/hpf) | Baseline up to 52 Weeks | Assessed for only those with duodenal involvement |
| Absolute change in EoG scores from the EoG Histology Scoring System (EoGHSS) | Baseline up to 52 Weeks | EoGHSS scores evaluate 11 features of gastric tissue. Total score is the sum of features scores divided by the maximum possible score for the biopsy. Total scores range from 0 - 1. |
| Percent change in peak gastric eosinophil count eosinophils/high power field (eos/hpf) | Baseline up to 52 Weeks | — |
Countries
Canada, Italy, Japan, United States
Contacts
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Outcome results
None listed