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

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ClinicalTrials.gov Identifier: NCT03933410
Recruitment Status : Recruiting
First Posted : May 1, 2019
Last Update Posted : August 13, 2019
Sponsor:
Information provided by (Responsible Party):
Kaleido Biosciences

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 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
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
Estimated Study Start Date : August 2019
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : July 2020


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




Primary Outcome Measures :
  1. 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 :
  1. 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 ]
  2. Incidence of adverse events (AEs) [ Time Frame: Day -28 to Day 84 ]
  3. Incidence of serious AEs (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)

  6. 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 ]
  7. Change from baseline to end of treatment in urinary concentration of PAGN [ Time Frame: Day -1, Day 56, Day 84 ]


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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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03933410


Contacts
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Contact: Margaret J Koziel, MD (617) 674-9000 clinicalstudies@kaleido.com

Locations
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United States, Florida
University of South Florida/ USF HEALTH Recruiting
Tampa, Florida, United States, 33606
Principal Investigator: Amarilis Sanchez-Valle, MD         
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
Principal Investigator: Kimihiko Oishi, MD         
United States, Pennsylvania
UPMC Children's Hospital of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15224
Principal Investigator: Gerard Vockley, MD         
Sponsors and Collaborators
Kaleido Biosciences
Investigators
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Study Director: Margaret J Koziel, MD Kaleido Biosciences

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Responsible Party: Kaleido Biosciences
ClinicalTrials.gov Identifier: NCT03933410     History of Changes
Other Study ID Numbers: K020-218
First Posted: May 1, 2019    Key Record Dates
Last Update Posted: August 13, 2019
Last Verified: August 2019

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

Keywords provided by Kaleido Biosciences:
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

Additional relevant MeSH terms:
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Disease
Urea Cycle Disorders, Inborn
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