Clinical trial NCT03933410: UNLOCKED: A Phase 2, Open-label Trial With KB195 in Subjects With a Urea Cycle Disorder
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
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
Lead sponsor: Kaleido Biosciences
Sponsor class: INDUSTRY
First posted: 2019-05-01
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: K020-218 is a single arm, open-label study
Primary purpose: TREATMENT

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.

Eligibility 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, 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

Primary outcomes:
measure: Proportion of subjects who achieve a ≥15% reduction from baseline in fasting plasma ammonia at the end of treatment.
timeFrame: Day -1 to Day 55
Secondary outcomes:
measure: 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.
timeFrame: Day -1 to Day 55
measure: Number of subjects experiencing adverse events (AEs)
timeFrame: Day -28 to Day 84
measure: Number of subjects experiencing severe adverse events (SAEs)
timeFrame: Day -28 to Day 84
measure: Change from baseline to end of treatment in Gastrointestinal Tolerability Questionnaire (GITQ) scores
timeFrame: Day -28 to Day 84
measure: Change from baseline to end of treatment in Bristol Stool Scale (BSS) scoring.
timeFrame: Day -28 to Day 84
Other outcomes:
Locations:
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Tampa
country: United States
facility: University of South Florida/ USF HEALTH
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai-Clinical Research Unit
state: New York
city: Pittsburgh
country: United States
facility: UPMC Children's Hospital of Pittsburgh
state: Pennsylvania
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Heidelberg
country: Germany
facility: Zentrum für Kinder- und Jugendmedizin Angelika-Lautenschläger-Klinik
city: Barakaldo
country: Spain
facility: Hospital de Cruces
city: Barcelona
country: Spain
facility: Hosptial Universitari Vall d'Hebron
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Bern
country: Switzerland
facility: Inselpital, Universitaetsklinik fur Kinderheikunde
city: Bern
country: Switzerland
facility: Inselpital, Universitätsklinik für Kinderheilkunde
city: Istanbul
country: Turkey
facility: Department of Child Health and Diseases, Department of Nutrition and Metabolism Istanbul University
city: Salford
country: United Kingdom
facility: Salford Royal Hospital
state: Greater Manchester
city: London
country: United Kingdom
facility: National Hospital for Neurology and Neurosurgery
city: Salford
country: United Kingdom
facility: Salford Royal NHS Foundation Trust
Study officials:
affiliation: Kaleido Biosciences
name: Mark Wingertzahn, PhD
role: STUDY_DIRECTOR
References: