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

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.

• KB195 (Drug): KB195 is a novel glycan

Primary outcomes

• 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

• 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]: 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. [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)

Sex: All, ages: 18 Years to 65 Years

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

• Mark Wingertzahn, PhD, Study director, Kaleido Biosciences