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

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

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

Study Overview

• Status: Terminated
• Conditions: Urea Cycle Disorder
• Intervention / Treatment: Drug: KB195

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 Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1200
    • Cliniques Universitaires Saint-Luc
  • Gent, Belgium, 9000
    • Universitair Ziekenhuis Gent
• Germany
  • Heidelberg, Germany, 69120
    • Zentrum für Kinder- und Jugendmedizin Angelika-Lautenschläger-Klinik
• Spain
  • Barakaldo, Spain, 48903
    • Hospital De Cruces
  • Barcelona, Spain, 08035
    • Hosptial Universitari Vall d'Hebron
  • Córdoba, Spain, 14004
    • Hospital Universitario Reina Sofia
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocío
• Switzerland
  • Bern, Switzerland, 3010
    • Inselpital, Universitaetsklinik fur Kinderheikunde
  • Bern, Switzerland, 3010
    • Inselpital, Universitätsklinik für Kinderheilkunde
• Turkey
  • Istanbul, Turkey
    • Department of Child Health and Diseases, Department of Nutrition and Metabolism Istanbul University
• United Kingdom
  • London, United Kingdom, WC1N3BG
    • National Hospital For Neurology and Neurosurgery
  • Salford, United Kingdom, M68HD
    • Salford Royal NHS Foundation Trust
  • Greater Manchester
    • Salford, Greater Manchester, United Kingdom, M68HD
      • Salford Royal Hospital
• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center
  • Florida
    • Tampa, Florida, United States, 33606
      • University of South Florida/ USF HEALTH
  • Maryland
    • Baltimore, Maryland, United States, 12105
      • Johns Hopkins University School of Medicine
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai-Clinical Research Unit
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • UPMC Children's Hospital of Pittsburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: KB195; KB195 is a novel glycan	Drug: KB195; KB195 is a novel glycan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Measure Description	Time Frame
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	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	Day -28 to Day 84
Change from baseline to end of treatment in Bristol Stool Scale (BSS) scoring.	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)	Day -28 to Day 84

Collaborators and Investigators

• Sponsor: Kaleido Biosciences

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 17, 2019
• Primary Completion (ACTUAL): February 2, 2021
• Study Completion (ACTUAL): March 2, 2021

Study Registration Dates

• First Submitted: April 29, 2019
• First Submitted That Met QC Criteria: April 29, 2019
• First Posted (ACTUAL): May 1, 2019

Study Record Updates

• Last Update Posted (ACTUAL): January 25, 2022
• Last Update Submitted That Met QC Criteria: January 20, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Microbiome; Quality of Life; Pediatric; Glutamine; Kaleido; Glycan; Urea Cycle Disorder; Elevated Ammonia; Disorder of the Urea Cycle Metabolism; KB195; UNLOCKED; Ornithine Transcarbamylase Deficiency (OTC); Carbamoyl Phosphatase Synthetase 1 (CPS1); Argininosuccinic Acid Synthetase (ASS1); Argininosuccinic Acid Lyase (ASL); Arginase (ARG 1); N-acetyl Glutamate Synthetase (NAGS); Ornithine Translocase (ORNT1); Microbiome Metabolic Therapy (MMT); Nitrogen Binding Therapy (NBT); Oligosaccharide
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Amino Acid Metabolism, Inborn Errors; Disease; Urea Cycle Disorders, Inborn
• Other Study ID Numbers: K020-218

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No