Elsiglutide will be administered to patients with colorectal cancer along with chemotherapy, to assess the efficacy of elsiglutide in preventing the Chemotherapy Induced Diarrhea (CID). Elsiglutide will be given at different doses including placebo group.

• Register: EUCTR
• Last refreshed on: 13 February 2017
• Main ID: EUCTR2014-000998-39-DE
• Date of registration: 08/07/2014
• Prospective Registration: Yes
• Primary sponsor: Helsinn Healthcare SA
• Public title: Elsiglutide will be administered to patients with colorectal cancer along with chemotherapy, to assess the efficacy of elsiglutide in preventing the Chemotherapy Induced Diarrhea (CID). Elsiglutide will be given at different doses including placebo group.
• Scientific title: Randomized, double-blind, parallel group, placebo-controlled, dose finding study in colorectal cancer patients receiving 5-FU-based chemotherapy to assess the efficacy of different doses of s.c. elsiglutide in the prevention of Chemotherapy Induced Diarrhea (CID)
• Date of first enrolment: 30/10/2014
• Target sample size: 600
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-000998-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belarus, Bulgaria, Czech Republic, Germany, Hungary, Russian Federation, Ukraine

Contacts

• Name: Regulatory Service
• Affiliation: Chiltern International Ltd

• Name: Regulatory Service
• Affiliation: Chiltern International Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
1. Written informed consent
2. Male or female patient > 18 years of age;
3. Histologically or cytologically confirmed diagnosis of colorectal cancer;
4.a) Inclusion in the Target Population:
Scheduled to receive at least 3 consecutive cycles of the same regimen of FOLFOX or FOLFIRI (Oxaliplatin/Irinotecan, Folinic acid, 5-FU) without monoclonal antibody;
4.b) Inclusion in the Additional Population:
Scheduled to receive at least 3 consecutive cycles of the same regimen of FOLFOX or FOLFIRI (Oxaliplatin/Irinotecan, Folinic acid, 5-FU) in combination with monoclonal antibody;
5. A performance status of = 2 according to the Eastern Cooperative Oncology Group (ECOG) scale;
6. Non-childbearing female patient or female patient of childbearing potential using reliable contraceptive measures and having negative pregnancy test before treatment administration;
7 Able to read, understand, follow the study procedure and complete patient diary.
Inclusion criteria will be checked during the screening visit. Inclusion criteria 4 and 6 will be re-checked as applicable on Day 1 of Cycle 1 and Cycle 2.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 300

Exclusion criteria:
Patients are excluded from this study if they meet any of the following criteria:
1. Any investigational drugs within 30 days before enrollment or foreseen use of investigational agents during the study;
2. Treatment with chemotherapy of any type within 12 months before enrollment;
3. Patient with any type of ostomy (temporary ostomy should be closed at least 6 months prior to enrollment);
4. Patient who underwent total colectomy;
5. Patient who had abdomino-perineal resection or surgery leaving the patient without a functioning rectum;
6. Any radiotherapy to the abdomen or pelvis in the 6 months prior to enrollment;
7. Scheduled to receive radiotherapy to abdomen or pelvis during the study;
8. a) Exclusion from the Target population
Scheduled to receive:
- any concomitant chemotherapeutic agent, other than FOLFOX or FOLFIRI agents (Oxaliplatin/Irinotecan, Folinic acid, 5-FU);
- any type of monoclonal antibodies;
8. b) Exclusion from the Additional population
Scheduled to receive:
- any concomitant chemotherapeutic agent, other than FOLFOX or FOLFIRI agents (Oxaliplatin/Irinotecan, Folinic acid, 5-FU;
9. Any type of condition leading to diarrhea, including but not limited to inflammatory bowel diseases (e.g. ulcerative colitis and Crohn’s disease), diarrhea of presumed or confirmed infectious origin and irritable bowel syndrome, celiac disease, lactose intolerance, pancreas, liver or diverticular disease, alcohol abuse;
10. History of chronic (= 30 consecutive days) use of laxatives;
11. Active and ongoing systemic infection;
12. Lactating woman;
13. History of hypersensitivity or allergies to drugs or compounds potentially related to this investigational drug class;
14. Previous exposure to GLP-2 or other compounds in this investigational drug class;
15. Patient who participated in a previous study with elsiglutide;
16. Patient with abnormalities in selected laboratory parameters, including:
a. Aspartate aminotransferase (AST) = 5 x upper limit of normal
b. Alanine aminotransferase (ALT) = 5 x upper limit of normal
c. Bilirubin > 1.5 x upper limit of normal
d. Creatinine > 2 mg/dL (177 µmol/L)
e. Albumine < 2 g/dL (20 g/L)
f. Neutrophils < 1.5 x109/L
g. Platelet count < 100 x109/L;
17. Any illness or condition that, in the opinion of the investigator, may confound the
results of the study or pose unwarranted risk in administering the investigational
product to the patient;
18. Any medical condition that precludes the administration of chemotherapy;
19. Use of laxatives within 7 days prior to study Day 1;
20. Use of antibiotics within 7 days prior to study Day 1;
21. Any diarrhea in the 48 hours preceding study drug administration on Day 1;
22. Major surgery within the previous 21 days before study Day 1;
23. Use of anti-diarrheal agents and probiotics within the 48 hours prior to study drug
administration on study Day 1.
Exclusion criteria 1 to 18 will be checked during the screening visit. Exclusion criteria 7,
8, 9, 11 and 17 to 23 will be checked on Day 1 of Cycle 1 and Cycle 2.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Chemotherapy Induced Diarrhea (CID)
MedDRA version: 18.1 Level: LLT Classification code 10056985 Term: Diarrhoea post chemotherapy System Organ Class: 100000004856

Intervention(s)

Product Name: Elsiglutide
Product Code: ZP1846
Pharmaceutical Form: Powder and solvent for suspension for injection
INN or Proposed INN: ELSIGLUTIDE
Other descriptive name: H-His-Gly-Glu-Gly-Ser-Phe-Ser-Ser-Glu-Leu-Ser-Thr-Ile-Leu-Asp-Ala-Leu-Ala-Ala-Arg-Asp-Phe-Ile-Ala-Trp-Leu-Ile-Ala-Thr-Lys-Ile-Thr-Asp-Lys-Lys-Lys-Lys-Lys-Lys-NH2, acetate salt (IUPAC)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Powder and solvent for suspension for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Secondary Objective: Efficacy of 3 s.c. elsiglutide doses vs placebo and vs each other dose in the prevention of CID in colorectal cancer patients treated with 5-FU based chemotherapy (FOLFOX or FOLFIRI) given in combination with a monoclonal antibody.
Safety and tolerability of the administered repeated doses of elsiglutide will be evaluated.
PK profile of elsiglutide and its active metabolites ZP2242 and ZP2712 in each patient who consents to undergo an exposure assessment after the 1st administration and at steady state (trough level only). Influence of possible demographic and therapeutic covariates on the PK parameters and their variability. The possible relationship between exposure of elsiglutide and its metabolites and efficacy measures in the target and overall population.
Economic impact of the 3 elsiglutide doses vs. placebo and each other dose in the treatment of CID.
Impact on patient’s QoL of the different elsiglutide dosages vs. placebo measured by Euroqol EQ-5D-3L questionnaire.

Primary end point(s): • Proportion of patients experiencing a maximum Grade = 2 diarrhea during the first cycle of chemotherapy.
This will be assessed for the Target population.

Timepoint(s) of evaluation of this end point: 14 days

Main Objective: The primary objective is to compare the efficacy of 3 s.c. doses of elsiglutide vs placebo and vs each other dose in the prevention of CID in colorectal cancer patients treated with 5-FU based chemotherapy (FOLFOX or FOLFIRI) with no addition of a monoclonal antibody.

Secondary Outcome(s)

Secondary end point(s): • Proportion of patients experiencing a maximum Grade = 2 diarrhea during the first cycle of chemotherapy in the Additional population.
The following endpoints will be considered for the Target population. They will also be considered for the Additional population as relevant based on the number of patients randomized in this population.
• Proportion of patients experiencing a maximum Grade = 2 diarrhea during the second and third cycle of chemotherapy;
• Proportion of patients experiencing a maximum Grade = 2 diarrhea over the first two cycles of chemotherapy (i.e. in at least one of the first two cycles);
• Proportion of patients experiencing a maximum Grade 1, Grade 2, Grade 3, Grade 4, Grade 5 and any Grade (i.e. = 1) diarrhea by cycle (Cycle 1, 2 and 3);
• Proportion of patients experiencing an overall Grade = 2 diarrhea by cycle (Cycle 1, Cycle 2 and Cycle 3);
• Proportion of patients experiencing an overall Grade = 2 diarrhea over the first two cycles of chemotherapy (i.e. in at least one of the first two cycles);
• Proportion of patients experiencing an overall Grade 1, Grade 2, Grade 3, Grade 4, Grade 5 and any Grade (i.e. = 1) by cycle (Cycle 1, 2 and 3);
• Time to onset of first event of diarrhea of any Grade (i.e. = 1) and time to onset of first event of diarrhea of Grade = 2 (as assessed by the Investigator) by cycle (Cycle 1, 2 and 3);
• Time to first day with diarrhea (as reported by patient in the eDiary) by cycle (Cycle 1, 2 and 3);
• Cumulative duration (days) of any Grade (i.e. = 1) diarrhea events and cumulative duration of Grade = 2 diarrhea events (as assessed by the Investigator) by cycle (Cycle 1, 2 and 3);
• Cumulative duration (days) of diarrhea events (as assessed by the Investigator) by grade (Grade 1, Grade 2, Grade 3, Grade 4, Grade 5) and by cycle (Cycle 1, 2 and 3);
• Number of events of diarrhea by grade (as assessed by the Investigator) by cycle (Cycle 1, 2 and 3);
• Number of days with presence of diarrhea (as reported by patient in the eDiary) by cycle (Cycle 1, 2 and 3);
• Number of days with presence of at least one bowel movement with stools of consistency 6 or 7 (according to Bristol Stool Form Scale) accompanied by urgency or by fecal incontinence by cycle (Cycle 1, 2 and 3);
• Number of days with presence of abdominal discomfort by cycle (Cycle 1, 2 and 3);
• Number of days with limitation of self-care activities due to diarrhea by cycle (Cycle 1, 2 and 3);
• Proportion of patients: who required i.v. fluids due to CID, who required changes to the primary therapy (chemotherapy dose reduction, delay or change to regimen) due to CID, who used rescue medication (i.e. medication used for treatment of diarrhea) by cycle (Cycle 1, 2 and 3);
• Proportion of patients having a maximum Grade = 2 diarrhea - shift from Cycle 1 to Cycle 2 and from Cycle 2 to Cycle 3;
• Proportion of patients having a maximum Grade = 1 diarrhea - shift from Cycle 1 to Cycle 2 and from Cycle 2 to Cycle 3;
• Proportion of patients having an overall Grade = 2 diarrhea - shift from Cycle 1 to Cycle 2 and from Cycle 2 to Cycle 3;
• Proportion of patients having an overall Grade = 1 diarrhea - shift from Cycle 1 to Cycle 2 and from Cycle 2 to Cycle 3;
• Time trend of the citrulline plasma concentrations in Cycles 1, 2 and 3.

Timepoint(s) of evaluation of this end point: 14 days

Secondary ID(s)

TIDE-13-22

73491

Source(s) of Monetary Support

Helsinn Healthcare SA