UNLOCKED: A Phase 2, Open-label Trial With KB195 in Subjects With a Urea Cycle Disorder (UNLOCKED)
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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
Urea Cycle Disorder
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 plasma ammonia levels, as measured by plasma ammonia 24-hour area under the curve. 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.
Change from baseline to end of treatment in the 24-hour area under the concentration-curve (AUC24) of plasma ammonia [ Time Frame: Day -1 to Day 84 ]
Secondary Outcome Measures :
Fasting ammonia concentration at baseline, during treatment, and end of treatment. [ Time Frame: Day -28, Day -1, Day 1, Day 28, Day 55, Day 56, Day 84 ]
Incidence of adverse events (AEs) [ Time Frame: Day -28 to Day 84 ]
Incidence of serious AEs (SAEs) [ Time Frame: Day -28 to Day 84 ]
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
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)
Change from baseline to end of treatment in concentrations (serum or plasma) of sodium benzoate (NaB), phenylbutyric acid (PBA), phenylacetic acid (PAA), and/or phenylacetylglutamine (PAGN) [ Time Frame: Day -1, Day 56, Day 84 ]
Change from baseline to end of treatment in urinary concentration of PAGN [ Time Frame: Day -1, Day 56, Day 84 ]
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Layout table for eligibility information
Ages Eligible for Study:
18 Years to 65 Years (Adult, Older Adult)
Sexes Eligible for Study:
Accepts Healthy Volunteers:
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 received a vaccination within 2 weeks before the Screening Visit
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