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

NCT03933410 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: K020-218
• Study Type: interventional
• Target: 13
• Locations: 7 countries
• Sites: 19

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

Conditions

Urea Cycle Disorder

Keywords

Microbiome; Elevated Ammonia; Disorder of the Urea Cycle Metabolism; Urea Cycle Disorder; KB195; Kaleido; 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); Glycan; Nitrogen Binding Therapy (NBT); Quality of Life; Oligosaccharide; Pediatric; Glutamine

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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

• Change from baseline to end of treatment in Bristol Stool Scale (BSS) scoring.

  Day -28 to Day 84

Study Arms (1)

KB195

EXPERIMENTAL

KB195 is a novel glycan

Drug: KB195

Interventions

KB195 DRUG

KB195 is a novel glycan

KB195

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Kaleido Biosciences: lead

Study Sites (19)

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

University of South Florida/ USF HEALTH

Tampa, Florida, 33606, United States

Location

Johns Hopkins University School of Medicine

Baltimore, Maryland, 12105, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Icahn School of Medicine at Mount Sinai-Clinical Research Unit

New York, New York, 10029, United States

Location

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Zentrum für Kinder- und Jugendmedizin Angelika-Lautenschläger-Klinik

Heidelberg, 69120, Germany

Location

Hospital de Cruces

Barakaldo, 48903, Spain

Location

Hosptial Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, 14004, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Inselpital, Universitaetsklinik fur Kinderheikunde

Bern, 3010, Switzerland

Location

Inselpital, Universitätsklinik für Kinderheilkunde

Bern, 3010, Switzerland

Location

Department of Child Health and Diseases, Department of Nutrition and Metabolism Istanbul University

Istanbul, Turkey (Türkiye)

Location

Salford Royal Hospital

Salford, Greater Manchester, M68HD, United Kingdom

Location

National Hospital for Neurology and Neurosurgery

London, WC1N3BG, United Kingdom

Location

Salford Royal NHS Foundation Trust

Salford, M68HD, United Kingdom

Location

MeSH Terms

Conditions

Urea Cycle Disorders, Inborn; Ornithine Carbamoyltransferase Deficiency Disease

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Genetic Diseases, X-Linked

Study Officials

• Mark Wingertzahn, PhD

  Kaleido Biosciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: K020-218 is a single arm, open-label study

Study Record Dates

• First Submitted: April 29, 2019
• First Posted: May 1, 2019
• Study Start: September 17, 2019
• Primary Completion: February 2, 2021
• Study Completion: March 2, 2021
• Last Updated: January 25, 2022

Record last verified: 2022-01

Locations

CH (2); DE (1); ES (4); GB (3); TU (1); BE (2); US (6)