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

• ClinicalTrials.gov Identifier: NCT03933410
• Recruitment Status: Recruiting
• First Posted: May 1, 2019
• Last Update Posted: March 12, 2020
• Sponsor: Kaleido Biosciences
• Information provided by (Responsible Party): Kaleido Biosciences

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 adult 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 and support the inclusion of pediatric patients as soon as possible.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: K020-218 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: September 17, 2019
• Estimated Primary Completion Date: October 2020
• Estimated Study Completion Date: November 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: KB195; KB195 is a novel glycan	Drug: KB195; KB195 is a novel glycan

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. 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. [ Time Frame: Day -1 to Day 55 ]
2. Number of subjects experiencing adverse events (AEs) [ Time Frame: Day -28 to Day 84 ]
3. Number of subjects experiencing severe adverse events (SAEs) [ Time Frame: Day -28 to Day 84 ]
4. Change from baseline to end of treatment in Gastrointestinal Tolerability Questionnaire (GITQ) scores [ Time Frame: 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
5. Change from baseline to end of treatment in Bristol Stool Scale (BSS) scoring. [ Time Frame: 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

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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, 18 to 65 years of age (inclusive)
• Has a BMI ≥20.0 and < 40.0 kg/m2
• 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

Contacts

Contact: Mark Wingertzahn, PhD; (617) 674-9000; clinicalstudies@kaleido.com

Locations

United States, District of Columbia

Children's National Medical Center; Recruiting

Washington, District of Columbia, United States, 20010

Principal Investigator: Nicholas Ah Mew, MD

United States, Florida

University of South Florida/ USF HEALTH; Recruiting

Tampa, Florida, United States, 33606

Contact: Emma Gonzalez 813-259-8813 egonzal2@usf.edu

Principal Investigator: Amarilis Sanchez-Valle, MD

United States, Maryland

Johns Hopkins University School of Medicine; Recruiting

Baltimore, Maryland, United States, 12105

Principal Investigator: Hilary Vernon, MD PhD

United States, Missouri

Washington University School of Medicine; Recruiting

Saint Louis, Missouri, United States, 63110

Principal Investigator: Marwan Shinawi, MD

United States, New York

Icahn School of Medicine at Mount Sinai-Clinical Research Unit; Recruiting

New York, New York, United States, 10029

Contact: Kate Graham-O'regan Katherine.Graham-oregan@mssm.edu

Contact Kimihiko.Oishi@mountsinai.org

Principal Investigator: Kimihiko Oishi, MD

United States, Pennsylvania

UPMC Children's Hospital of Pittsburgh; Recruiting

Pittsburgh, Pennsylvania, United States, 15224

Contact: Mark Tumblin 412-692-5969 mark.tumblin2@chp.edu

Principal Investigator: Gerard Vockley, MD

Belgium

Cliniques Universitaires Saint-Luc; Recruiting

Bruxelles, Belgium, 1200

Principal Investigator: Etienne Sokal, MD PhD

Universitair Ziekenhuis Gent; Recruiting

Gent, Belgium, 9000

Principal Investigator: Patrick Verloo, MD

Spain

Hospital de Cruces; Recruiting

Barakaldo, Spain, 48903

Principal Investigator: Luis Aldamiz-Echevarria Azuara, MD

Hosptial Universitari Vall d'Hebron; Recruiting

Barcelona, Spain, 08035

Principal Investigator: Guillem Pintos Morell, MD

Hospital Universitario Reina Sofia; Recruiting

Córdoba, Spain, 14004

Principal Investigator: Mercedes Gil Campos, MD

Hospital Universitario Virgen del Rocio; Recruiting

Sevilla, Spain, 41013

Principal Investigator: Eva Venegas Moreno, MD

Switzerland

Inselpital, Universitaetsklinik fur Kinderheikunde; Recruiting

Bern, Switzerland, 3010

Principal Investigator: Matthias Gautschi, MD PhD

United Kingdom

Salford Royal Hospital; Recruiting

Salford, Greater Manchester, United Kingdom, M68HD

Principal Investigator: Reena Sharma, MD

National Hospital for Neurology and Neurosurgery; Recruiting

London, United Kingdom, WC1N3BG

Principal Investigator: Robin Lachmann, MD

Sponsors and Collaborators

Kaleido Biosciences

Investigators

• Study Director: Mark Wingertzahn, PhD; Kaleido Biosciences

More Information

• Responsible Party: Kaleido Biosciences
• ClinicalTrials.gov Identifier: NCT03933410
• Other Study ID Numbers: K020-218
• First Posted: May 1, 2019
• Last Update Posted: March 12, 2020
• Last Verified: March 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Kaleido Biosciences:

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

Additional relevant MeSH terms:

Urea Cycle Disorders, Inborn; Disease; Pathologic Processes; 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; Metabolic Diseases