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

Urea Cycle Disorder Clinical Trial

— UNLOCKED  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03933410
• Other study ID #: K020-218
• Status: Terminated
• Phase: Phase 2
• Start date: September 17, 2019
• Est. completion date: March 2, 2021

Study information

• Verified date: January 2022
• Source: Kaleido Biosciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Terminated
• Enrollment: 13
• Est. completion date: March 2, 2021
• Est. primary completion date: February 2, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Disease
• Urea Cycle Disorder
• Urea Cycle Disorders, Inborn

Intervention

Drug:
• KB195
KB195 is a novel glycan

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint-Luc	Bruxelles
Belgium	Universitair Ziekenhuis Gent	Gent
Germany	Zentrum für Kinder- und Jugendmedizin Angelika-Lautenschläger-Klinik	Heidelberg
Spain	Hospital de Cruces	Barakaldo
Spain	Hosptial Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario Reina Sofia	Córdoba
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Switzerland	Inselpital, Universitaetsklinik fur Kinderheikunde	Bern
Switzerland	Inselpital, Universitätsklinik für Kinderheilkunde	Bern
Turkey	Department of Child Health and Diseases, Department of Nutrition and Metabolism Istanbul University	Istanbul
United Kingdom	National Hospital for Neurology and Neurosurgery	London
United Kingdom	Salford Royal Hospital	Salford	Greater Manchester
United Kingdom	Salford Royal NHS Foundation Trust	Salford
United States	Johns Hopkins University School of Medicine	Baltimore	Maryland
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	Washington University School of Medicine	Saint Louis	Missouri
United States	University of South Florida/ USF HEALTH	Tampa	Florida
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Kaleido Biosciences

Countries where clinical trial is conducted

United States,  Belgium,  Germany,  Spain,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Number of subjects experiencing adverse events (AEs)		Day -28 to Day 84
Secondary	Number of subjects experiencing severe adverse events (SAEs)		Day -28 to Day 84
Secondary	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
Secondary	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