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

Phase 2

Terminated

Conditions: Urea Cycle Disorder

Interventions: Drug: KB195

Registration Number: NCT03933410

Lead Sponsor: Kaleido Biosciences

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

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 13

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
KB195	KB195	KB195 is a novel glycan

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
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
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)

Trial Locations

Locations (19): Salford Royal NHS Foundation Trust
🇬🇧
Salford, United Kingdom
Department of Child Health and Diseases, Department of Nutrition and Metabolism Istanbul University
🇹🇷
Istanbul, Turkey
Hospital Universitario Virgen del Rocio
🇪🇸
Sevilla, Spain
Hospital de Cruces
🇪🇸
Barakaldo, Spain
Hosptial Universitari Vall d'Hebron
🇪🇸
Barcelona, Spain
University of South Florida/ USF HEALTH
🇺🇸
Tampa, Florida, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
Icahn School of Medicine at Mount Sinai-Clinical Research Unit
🇺🇸
New York, New York, United States
UPMC Children's Hospital of Pittsburgh
🇺🇸
Pittsburgh, Pennsylvania, United States
Zentrum für Kinder- und Jugendmedizin Angelika-Lautenschläger-Klinik
🇩🇪
Heidelberg, Germany
Hospital Universitario Reina Sofia
🇪🇸
Córdoba, Spain
Salford Royal Hospital
🇬🇧
Salford, Greater Manchester, United Kingdom
Universitair Ziekenhuis Gent
🇧🇪
Gent, Belgium
Inselpital, Universitaetsklinik fur Kinderheikunde
🇨🇭
Bern, Switzerland
Johns Hopkins University School of Medicine
🇺🇸
Baltimore, Maryland, United States
Inselpital, Universitätsklinik für Kinderheilkunde
🇨🇭
Bern, Switzerland
Cliniques Universitaires Saint-Luc
🇧🇪
Bruxelles, Belgium
Children's National Medical Center
🇺🇸
Washington, District of Columbia, United States
National Hospital for Neurology and Neurosurgery
🇬🇧
London, United Kingdom