Metabolic Balance Study of FE203799 in Patients With SBS With Intestinal Insufficiency

SBS - Short Bowel Syndrome Clinical Trial

Official title:

A Phase Ib/IIa Open-label, Repeated Dose, Metabolic Balance Study of FE 203799 in Patients With Short Bowel Syndrome and Intestinal Insufficiency

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03408132
• Other study ID #: GLY-321-2017
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: May 2, 2018
• Est. completion date: October 28, 2019

Study information

• Verified date: February 2020
• Source: VectivBio AG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a repeated dose, open label trial investigating safety, efficacy, PD and PK of FE 203799 in 8 patients with SBS. The patients will receive a subcutaneous (SC) dose of 5 mg FE 203799 once weekly for 4 consecutive weeks, and efficacy parameters and PK will be assessed after the fourth dose. Safety follow up assessments will be performed 4-6 weeks after the last dose.

Description:

This is a repeated dose, open label trial investigating safety, efficacy, PD and PK of FE 203799 in 8 patients with SBS . The patients will receive a subcutaneous (SC) dose of 5 mg FE 203799 once weekly for 4 consecutive weeks, and efficacy parameters and PK will be assessed after the fourth dose. Safety follow-up assessments will be performed 4-6 weeks after the last dose.

The first two administrations of trial drug will be performed at the clinic, while the third dose can be either self-administered by the patient or administered at the clinic if the patient prefers to travel to the site or other considerations make a site visit preferable. The fourth administration of trial drug will be performed at the clinic just prior to assessment of efficacy parameters in the treatment balance study.

Prior to each administration of trial drug, liver function parameters will be analysed and assessed. During the entire trial, patients who develop extremely high or persistently elevated liver enzymes following trial drug administration will be discontinued from the trial.

The patients will complete a diary with data on trial drug administration performed at home, local tolerability and adverse events (AEs).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: October 28, 2019
• Est. primary completion date: October 28, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Males and females with SBS secondary to surgical resection of the small intestine, with or without an intact colon.

2. 18-80 years of age

3. Average faecal wet weight excretion of =1500 g/day during the baseline balance study

4. Average urine production <2000 mL/day during the baseline balance study

5. Body Mass Index (BMI) between 16.0 and 32.0 (both inclusive)

6. At least 6 months since last surgical bowel resection

7. Willing to adhere to a defined oral intake of fluids on certain days as required by the protocol (and based on the individual's routine daily consumption)

8. Women of childbearing potential must agree to use an adequate method of contraception during the trial and for 60 days after the end-of-trial visit. Adequate methods of contraception include intrauterine device or hormonal contraception (oral contraceptive pill, depot injections or implant, transdermal depot patch or vaginal ring). To be considered sterilised or infertile, females must have undergone surgical sterilisation (bilateral tubectomy, hysterectomy or bilateral ovariectomy) or be post-menopausal (defined as at least 12 months amenorrhoea and confirmed with follicle-stimulating hormone [FSH] test)

Exclusion Criteria:

1. Pregnancy or lactation

2. Positive results on the human immunodeficiency virus (HIV), hepatitis B and/or C tests

3. A history of clinically significant intestinal adhesions and/or chronic abdominal pain

4. Require chronic systemic narcotics for treatment of pain that exceeds an amount corresponding to 80 mg of morphine per day

5. History of cancer or clinically significant lymphoproliferative disease within =5 years, except for adequately treated basal cell skin cancer

6. History of gallstone within the past 3 years. Gallstone with subsequent cholecystectomy to resolve the issues is acceptable.

7. Inflammatory bowel disease patients (IBD) who have NOT been on a stable drug treatment regimen for at least the past 4 weeks

8. Evidence of active IBD in the past 12 weeks

9. Visible blood in the stool within the last 3 months

10. Decompensated heart failure (New York Heart Association [NYHA] class III-IV, see Appendix 12.2) and/or known coronary heart disease defined as unstable angina pectoris and/or myocardial infarction within the last 6 months prior to screening

11. Radiation enteritis, scleroderma or other condition of intestinal dysmotility, coeliac disease, refractory or tropical sprue

12. History of alcohol and/or drug abuse within the last 12 months

13. Inadequate hepatic function as defined by: bilirubin >upper limit of normal (ULN), alanine transaminase (ALT) or aspartate transaminase (AST) >2.0 × ULN; alkaline phosphatase (ALP) >2.5 × ULN; or international normalised ratio (INR) >1.5 × ULN

14. Inadequate renal function as defined by serum creatinine or blood urea nitrogen >2.5 x ULN

15. Unplanned hospitalisation of >24 hours duration within 1 month before the screening visit

16. Systemic corticosteroids, methotrexate, cyclosporine, tacrolimus, sirolimus, infliximab, or other biologic therapy/immune modifiers within 30 days of screening

17. Any use of growth hormone, glutamine or growth factors such as native GLP-2 or GLP-2 analogue within the last 3 months

18. Any use of antibiotics within the last 30 days

19. Participation in another clinical trial within the last 3 months and during this trial

20. Previously been treated in this trial

21. Loss of blood or donation of blood or plasma >500 mL within 3 months prior to screening

22. Patient not capable of understanding or not willing to adhere to the trial visit schedules and other protocol requirements

23. For any other reason judged not eligible by the investigator

Related Conditions & MeSH terms

• SBS - Short Bowel Syndrome
• Short Bowel Syndrome
• Syndrome

Intervention

Drug:
• FE203799
FE203799 5 mg subcutaneous once weekly

Locations

Country	Name	City	State
Denmark	Rigshospitalet	Copenhagen

Sponsors (2)

Lead Sponsor	Collaborator
GlyPharma Therapeutics	VectivBio AG

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment-emergent adverse events	Adverse events as assessed by CTCAE v4.03	Day -28 to Day 26 plus 6 weeks
Secondary	Assessment of intestinal insufficiency and gut absorption	Changes in the wet weight (g) of faecal excretion	Day -28 to day 26
Secondary	Assessment of intestinal insufficiency and gut absorption	Changes from baseline in lean body mass by DEXA scan.	Day -28 and day 26
Secondary	Assessment of intestinal insufficiency and gut absorption	Changes from baseline in bone mineral content by DEXA scan.	Day -28 and day 26
Secondary	Assessment of intestinal insufficiency and gut absorption	Changes from baseline in fat mass by DEXA scan.	Day -28 and day 26
Secondary	Assessment of intestinal insufficiency and gut absorption	Measure of body weight (kg)	Day -28 to day 26 plus 6 weeks
Secondary	Assessment of intestinal insufficiency and gut absorption	Measurement of urinary output (ml)	Baseline (Day -6) to end of treatment (Day 26)
Secondary	Assessment of intestinal insufficiency and gut absorption	Measurement of urinary electrolytes (sodium, potassium, calcium, magnesium) (mmol/d)	Baseline (Day -6) to end of treatment (Day 26)
Secondary	Assessment of gut regeneration	Measurements of the plasma Citrulline (ng/ml)	Baseline (Day -7) to end of treatment period (Day 26) plus 6 weeks
Secondary	Maximum observed plasma concentration (Cmax)	Cmax (ng/ml)	Day 1 to end of treatment period (Day 26)
Secondary	Cumulative area under the plasma concentration (AUC) of FE 203799 from time 0 to 168	AUC0-168 (ng*hr/ml)	Day 1 to end of treatment period (Day 26)
Secondary	Terminal elimination half-life (T1/2) of FE 203799	T1/2 (h)	Day 1 to end of treatment period (Day 26)
Secondary	Apparent total body clearance (CL) of FE 203799 from plasma	CL (ml/hr)	Day 1 to end of treatment period (Day 26)
Secondary	Apparent volume of distribution (Vd) of FE 203799 during terminal phase	Vd (ml)	Day 1 to end of treatment period (Day 26)