VIBRANT Study of Vurolenatide in Adult Patients With Short Bowel Syndrome.

Study Overview
=================
Brief Summary
-----------------
A Study of Vurolenatide in Adult Patients with Short Bowel Syndrome.

Detailed Description
-----------------
A Phase 2 study of Vurolenatide in adult patients with SBS. Patients were planned to be dosed in four treatment groups with placebo and/or active Vurolenatide. The study is 13 weeks (3 weeks screening, 4 weeks SC study drug administration, and 6 weeks of follow up). Safety and efficacy will be analyzed.

Official Title
-----------------
A Phase 2, Double-Blind, Double-Dummy, Placebo-Controlled, Multicenter Study of the Efficacy, Safety, and Tolerability of Vurolenatide in Adult Patients With Short Bowel Syndrome

Conditions
-----------------
Short Bowel Syndrome

Intervention / Treatment
-----------------
* Drug: Vurolenatide 50mg/PBO
* Drug: Vurolenatide 100mg/PBO
* Drug: Vurolenatide 50/50 mg
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Criteria for patient inclusion in this study are as follows: Male and female adults with SBS secondary to surgical resection of small intestine 18-75 years of age at the time of screening. Female patients must be postmenopausal (at least 2 years prior to dosing) or surgically sterile or agree to use an acceptable form of birth control from screening until 30 days after last dose. If oral contraceptives are used, patients must have been on a stable dose for ≥6 months. Male patients must agree to use an acceptable form of birth control during the study and for 30 days after the last dose. Male patients should not donate sperm for 90 days after last dose. At least 6 months since last surgical bowel resection. Patients may be on Parenteral Support [PS] (nutrition and/or fluid and electrolytes for at least some of their nutritional needs). If on PS, stable administration of PS volume for 1 month (±20% vol) prior to enrollment [stable administration of PS volume confirmed by Medical Monitor]. Able to ingest solid or semi-solid foods and drink. Key Exclusion Criteria: Criteria for exclusion from participation in this study are presented below. Pregnancy or lactation Body mass index at screening <18 or >30 kg/m2 Clinically significant intestinal adhesions and/or chronic abdominal pain that can interfere with the conduct of the study Active Crohn's disease or IBD (as evaluated by standard procedures employed by the investigator/institution). If in remission, must be ≥12 weeks of remission prior to screening Inflammatory bowel disease patients who have NOT been on a stable drug treatment regimen for at least the past 3 months prior to screening Visible blood in the stool within the last 3 months Known heart failure or active coronary disease Alcohol or drug abuse within the last 12 months by history, or a disqualifying positive urine drug test at screening. Inadequate renal function as defined by serum creatinine <0.7 or >1.3 mg/dL (in men) and <0.6 or >1.1 mg/dL in women. Personal or family history of medullary thyroid cancer. History of pancreatitis Any use of growth hormone, or growth factors such as native GLP-2 or GLP-2 analog (teduglutide) within the last 3 months Use of antibiotics within the last 30 days Patient not capable of understanding or not willing to adhere to the study visit schedules and other protocol requirements

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Double-Blind, Double-Dummy, Placebo-Controlled.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vurolenatide 50 mg/PBO<br>50 mg biweekly SC administration, PBO alternate weeks | Drug: Vurolenatide 50mg/PBO<br>* Vurolenatide - 50 mg biweekly SC administration, PBO alternate weeks<br>|
| Active Comparator: Vurolenatide 100 mg/PBO<br>100 mg biweekly SC administration, PBO alternate weeks | Drug: Vurolenatide 100mg/PBO<br>* Vurolenatide - 100 mg biweekly SC administration, PBO alternate weeks<br>|
| Active Comparator: Vurolenatide 50/50 mg<br>50 mg weekly SC administration | Drug: Vurolenatide 50/50 mg<br>* Vurolenatide - 50 mg weekly SC administration<br>|
| Placebo Comparator: Placebo<br>PBO - weekly SC administration | Drug: Placebo<br>* PBO - weekly SC administration<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24hr total stool output volume | The primary outcome measure is 24hr total stool output volume over the double-blind treatment period compared to baseline. | 10 weeks (including 6 weeks follow up) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the safety and tolerability of vurolenatide | Assessment of Adverse events - The frequency of spontaneously reported AEs will be assessed for each treatment group separately by System Organ Class and Preferred Term; and vital signs, physical examination results, clinical laboratory tests results will be evaluated. | 10 weeks (including 6 weeks follow up) | 
| To assess change from Baseline in Quality of Life | Change from baseline in Quality of Life as measured by the SF-36 instrument over the double-blind treatment period | 10 weeks (including 6 weeks follow up) | 
| To assess the change from baseline in Patient Global Impression | Change from baseline in patient reported global SBS improvement over the double-blind treatment period | 10 weeks (including 6 weeks follow up) |