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出境医 / 临床实验 / UNLOCKED: A Phase 2, Open-label Trial With KB195 in Subjects With a Urea Cycle Disorder (UNLOCKED)

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

Study Description
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 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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: N/A
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
Actual Study Start Date : September 17, 2019
Estimated Primary Completion Date : October 2021
Estimated Study Completion Date : November 2021
Arms and Interventions
Arm Intervention/treatment
Experimental: KB195
KB195 is a novel glycan
 Drug: KB195
KB195 is a novel glycan
Outcome Measures
Primary Outcome Measures :
  1. Proportion of subjects who achieve a ≥15% reduction from baseline in fasting plasma ammonia at the end of treatment. [ Time Frame: Day -1 to Day 55 ]

Secondary Outcome Measures :
  1. 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. [ Time Frame: Day -1 to Day 55 ]
  2. Number of subjects experiencing adverse events (AEs) [ Time Frame: Day -28 to Day 84 ]
  3. Number of subjects experiencing severe adverse events (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)


Eligibility Criteria
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Ages Eligible for Study:   12 Years to 70 Years   (Child, 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, 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
Contacts and Locations

Contacts
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Contact: Mark Wingertzahn, PhD (617) 674-9000 clinicalstudies@kaleido.com

Locations
Show Show 19 study locations
Sponsors and Collaborators
Kaleido Biosciences
Investigators
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Study Director: Mark Wingertzahn, PhD Kaleido Biosciences
Tracking Information
First Submitted Date  ICMJE April 29, 2019
First Posted Date  ICMJE May 1, 2019
Last Update Posted Date October 8, 2020
Actual Study Start Date  ICMJE September 17, 2019
Estimated Primary Completion Date October 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 10, 2020) 		Proportion of subjects who achieve a ≥15% reduction from baseline in fasting plasma ammonia at the end of treatment. [ Time Frame: Day -1 to Day 55 ]
Original Primary Outcome Measures  ICMJE
 (submitted: April 29, 2019) 		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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 10, 2020)
  • 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. [ Time Frame: Day -1 to Day 55 ]
  • Number of subjects experiencing adverse events (AEs) [ Time Frame: Day -28 to Day 84 ]
  • Number of subjects experiencing severe adverse events (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)
Original Secondary Outcome Measures  ICMJE
 (submitted: April 29, 2019)
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE UNLOCKED: A Phase 2, Open-label Trial With KB195 in Subjects With a Urea Cycle Disorder
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
K020-218 is a single arm, open-label study
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Urea Cycle Disorder
Intervention  ICMJE Drug: KB195
KB195 is a novel glycan
Study Arms  ICMJE Experimental: KB195
KB195 is a novel glycan
Intervention: Drug: KB195
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 2, 2019) 		24
Original Estimated Enrollment  ICMJE
 (submitted: April 29, 2019) 		30
Estimated Study Completion Date  ICMJE November 2021
Estimated Primary Completion Date October 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years to 70 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Mark Wingertzahn, PhD (617) 674-9000 clinicalstudies@kaleido.com
Listed Location Countries  ICMJE Belgium,   Germany,   Spain,   Switzerland,   Turkey,   United Kingdom,   United States
Removed Location Countries Mexico
 
Administrative Information
NCT Number  ICMJE NCT03933410
Other Study ID Numbers  ICMJE K020-218
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Kaleido Biosciences
Study Sponsor  ICMJE Kaleido Biosciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Mark Wingertzahn, PhD Kaleido Biosciences
PRS Account Kaleido Biosciences
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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