UNLOCKED: A Phase 2, Open-label Trial With KB195 in Subjects With a Urea Cycle Disorder

Sponsor

Kaleido Biosciences (Industry)

Overall Status

Terminated

CT.gov ID

NCT03933410

Collaborator

(none)

Enrollment

Locations

Arm

17.5

Actual Duration (Months)

0.7

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

UNLOCKED: A Phase 2 Trial to Evaluate the Efficacy and Safety of KB195 in Subjects with a Urea Cycle Disorder with Inadequate Control on Standard of Care

Condition or Disease	Intervention/Treatment	Phase
Urea Cycle Disorder	Drug: KB195	Phase 2

Detailed Description

We expect the trial to enroll approximately 24 Urea Cycle Disorder (UCD) patients on standard of care with elevated ammonia levels. The planned treatment duration is eight weeks, with a primary endpoint of proportion of subjects who achieve a ≥15% reduction from baseline in fasting ammonia at the end of treatment. Patients will also be followed for safety and tolerability. This clinical trial is intended to allow us to evaluate efficacy of KB195 in reducing ammonia in UCD patients.

Study Design

Study Type:

Interventional

Actual Enrollment :

13 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

K020-218 is a single arm, open-label studyK020-218 is a single arm, open-label study

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 2, Open-label Study to Evaluate the Efficacy and Safety of KB195 in Subjects With A Urea Cycle Disorder With Inadequate Control on Standard of Care

Actual Study Start Date :

Sep 17, 2019

Actual Primary Completion Date :

Feb 2, 2021

Actual Study Completion Date :

Mar 2, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: KB195 KB195 is a novel glycan	Drug: KB195 KB195 is a novel glycan

Arm

Intervention/Treatment

Experimental: KB195

KB195 is a novel glycan

Drug: KB195

KB195 is a novel glycan

Outcome Measures

Primary Outcome Measures

Proportion of subjects who achieve a ≥15% reduction from baseline in fasting plasma ammonia at the end of treatment. [Day -1 to Day 55]

Secondary Outcome Measures

Proportion of subjects normalizing their fasting plasma ammonia concentrations from above the upper limit of normal at baseline to below the upper limit of normal at the end of treatment. [Day -1 to Day 55]
Number of subjects experiencing adverse events (AEs) [Day -28 to Day 84]
Number of subjects experiencing severe adverse events (SAEs) [Day -28 to Day 84]
Change from baseline to end of treatment in Gastrointestinal Tolerability Questionnaire (GITQ) scores [Day -28 to Day 84]
Evaluate the effect of KB195 on self-report questionnaires including the Gastrointestinal Tolerability Questionnaire, an assessment of the frequency and severity of GI symptoms, e.g., gas, abdominal pain, calculated on a scale from 0 (None/Not applicable) to a maximum score of 60 (Severe/Much more than usual) for all questions
Change from baseline to end of treatment in Bristol Stool Scale (BSS) scoring. [Day -28 to Day 84]
Evaluate the effect of KB195 on self-report questionnaires including the Bristol Stool Scale, an assessment of stool consistency on a scale from 1 (separate hard lumps, like nuts, hard to pass) through 7 (watery, no solid pieces, entirely liquid)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Signed informed consent and willing to comply with protocol-specified procedures.
Has any confirmed UCD other than N-acetyl glutamatesynthase (NAGS) deficiency.
Is male or female, 12 to 70 years of age (inclusive)
If ≥ 18 years old, has a BMI ≥20.0 and < 40.0 kg/m2. If < 18 years old, has a BMI between 5th percentile and 95th percentile and weight greater than 5th percentile according to age, sex and regionally appropriate growth chart
Has evidence of poorly controlled disease on the current standard of care (SOC)
If NBT is part of SOC, is on a stable dose and regimen for at least 4 weeks before Screening and the dose is expected to remain stable during the study
Is willing to maintain a stable diet throughout the course of study and is willing to continue usual exercise routine.
If taking probiotics or prebiotics, is on a stable dose regimen for at least 4 weeks before Screening and the dose and regimen are expected to remain stable during the study
Has a negative urine screen for drugs of abuse at Screening
If male or female of child bearing potential, agree with use effective method of contraception for the duration of the study and 90 days after last dose of study product

Key Exclusion Criteria:

Is at a high risk for metabolic decomposition.
Has had a substantive change in diet or any other aspect of UCD management within 4 weeks before the Screening Visit
Has used a systemic anti-infective within 4 weeks before the Screening Visit, or use is anticipated during the study
Has been diagnosed with Citrullinemia Type II
Is receiving any systemically administered immunosuppressant medication on a chronic basis
Has changed the use of or dose of any drug or other compound to modulate GI motility within 4 weeks before the Screening Visit, or the use or dose is expected change during the course of the study
Has a history of or active GI or liver disease
Has a prior solid organ transplantation including liver transplantation, or is anticipated to receive a liver transplant during study participation
Has used an investigational drug, product, or device within 30 days before the Screening Visit
Has a contraindication, sensitivity, or known allergy to the study drug
Is considered, in the opinion of the PI, to likely be a poor attendee or unlikely for any reason to be able to comply with the study drug procedures

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's National Medical Center	Washington	District of Columbia	United States	20010
2	University of South Florida/ USF HEALTH	Tampa	Florida	United States	33606
3	Johns Hopkins University School of Medicine	Baltimore	Maryland	United States	12105
4	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
5	Icahn School of Medicine at Mount Sinai-Clinical Research Unit	New York	New York	United States	10029
6	UPMC Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15224
7	Cliniques Universitaires Saint-Luc	Bruxelles		Belgium	1200
8	Universitair Ziekenhuis Gent	Gent		Belgium	9000
9	Zentrum für Kinder- und Jugendmedizin Angelika-Lautenschläger-Klinik	Heidelberg		Germany	69120
10	Hospital de Cruces	Barakaldo		Spain	48903
11	Hosptial Universitari Vall d'Hebron	Barcelona		Spain	08035
12	Hospital Universitario Reina Sofia	Córdoba		Spain	14004
13	Hospital Universitario Virgen del Rocio	Sevilla		Spain	41013
14	Inselpital, Universitaetsklinik fur Kinderheikunde	Bern		Switzerland	3010
15	Inselpital, Universitätsklinik für Kinderheilkunde	Bern		Switzerland	3010
16	Department of Child Health and Diseases, Department of Nutrition and Metabolism Istanbul University	Istanbul		Turkey
17	Salford Royal Hospital	Salford	Greater Manchester	United Kingdom	M68HD
18	National Hospital for Neurology and Neurosurgery	London		United Kingdom	WC1N3BG
19	Salford Royal NHS Foundation Trust	Salford		United Kingdom	M68HD