International multicenter study to test the efficacy and safety of a new drug, KB195, in subjects with Urea Cycle Disorder with an inadequate control of the disease with current standard drugs.

Phase 1

• Conditions: Subjects with a Urea Cycle Disorder with Inadequate Control on Standard of Care; MedDRA version: 20.1Level: PTClassification code 10080020Term: Urea cycle disorderSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2018-004842-40-FR
• Lead Sponsor: Kaleido Biosciences

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-11-18
• Last Update Posted: 13 December 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 29

Inclusion Criteria

1. Is able and willing, or has a legally authorized representative (LAR) who is able and willing, to give written informed consent. When the LAR provides informed consent, the subject must also provide written assent if able.
2. Is willing to comply with specified procedures as stated in the protocol
3. Has any confirmed UCD other than N-acetylglutamate synthase (NAGS) deficiency, with the diagnosis confirmed through genetic testing, enzymatic analysis, or analysis of ammonia and amino acid concentrations, as appropriate for the UCD subtype; documentation may be from the historical record
4. Is male or female, 18 to 65 years of age (inclusive)
5. Has a body mass index (BMI) = 20.0 and < 40.0 kg/m2
6. Has evidence of poorly controlled disease on the current SOC, as evidenced by at least 2 fasting plasma ammonia concentrations > ULN within 6 months before Day -1 (one of which may be during the Screening Period)
7. If NBT is part of SOC, is on a stable dose and regimen of NBT for at least 4 weeks before Screening and the dose is expected to remain stable during the study
8. Is willing to maintain a stable diet throughout the course of the study, and is willing to continue usual exercise routine
9. Is willing to continue taking any current supplements and vitamins (with the exception of prebiotic or probiotic supplements) that the subject is currently taking, for the duration of the study
10. If taking probiotics or prebiotics, is on a stable dose and regimen for at least 4 weeks before Screening and the dose and regimen are expected to remain stable during the study
11. Has negative urine screen for drugs of abuse at Screening
12. If subject is female: subject is surgically sterile or post-menopausal (12 months with no menses without an alternate medical cause); or if subject is a female of childbearing potential (FCBP), must have a negative serum pregnancy test at Screening, must not be lactating, and must agree to abstain from sexual activity or agree to use a highly effective method of contraception for the duration of the study and for 30 days after the last dose of KB195
13. If subject is male and has a female partner of childbearing potential, must agree to abstain from sexual activity or agree to use a highly effective contraceptive method for the duration of the study and for 90 days after the last dose of KB195
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 28
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1

Exclusion Criteria

1. Is at high risk for metabolic decompensation, as indicated by:
- More than 4 hospitalizations within 1 year before the Screening Visit for management of acute metabolic decompensation due to UCD, OR
- An ammonia concentration of = 100 µmol/L with clinical signs or symptoms during Screening (if a subject meets all other study requirements, at the PI’s discretion the subject may be re-screened 1 time after their ammonia is controlled and clinical symptoms have resolved), OR
- Other evidence of metabolic instability as judged by the PI.
2. Has had a substantive change (as judged by the PI) in diet or any other aspect of UCD management within 4 weeks before the Screening Visit
3. Has used a systemic anti-infective (for example, an antibiotic, antifungal, or antiviral product) within 4 weeks before the Screening Visit, or use is anticipated during the study (if a subject fails this criterion and meets all other study requirements, at the PI’s discretion and after consultation with the Sponsor, the subject may be re-screened 1 time)
4. Has been diagnosed with Citrullinemia Type II
5. Is receiving any systemically administered immunosuppressant medication on a chronic basis at a dose > 10 mg/day of prednisone or equivalent
6. Has changed the use or dose of any drug or other compound to modulate GI motility (including stool softeners, laxatives, bismuth, or fiber supplements), within 4 weeks before the Screening Visit, or the use or dose is expected change during the course of the study. Note that proton pump inhibitors and antacids are permitted, provided they are taken at baseline and continued throughout the study. (If a subject fails this criterion and meets all other study requirements, at the PI’s discretion the subject may be re-screened 1 time)
7. Has a history of or active GI or liver disease that may affect assessment of the efficacy, safety, or tolerability of KB195, including but not limited to the following: chronic diarrhea, malabsorption syndrome, inflammatory bowel disease, irritable bowel syndrome, liver cirrhosis or failure, autoimmune disease, or GI malignancy
8. Has a clinically significant or uncontrolled concomitant illness that would put the subject at risk or jeopardize the objectives of the study
9. Has a prior solid organ transplantation including liver transplantation, or is anticipated to receive a liver transplant during study participation
10. Has used an investigational drug, product, or device within 30 days before the Screening Visit; or is enrolled in another investigational drug, product, or device study within 30 days before the Screening Visit
11. Has a contraindication, sensitivity, or known allergy to any ingredient of the study drug
12. 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 procedures (for example, planned procedures or traveling that would occur during the duration of the study)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Evaluate the efficacy of KB195 in ammonia lowering, when added to Standard Of Care (SOC), in subjects with a Urea Cycle Disorder (UCD).;Secondary Objective: • Evaluate the safety and tolerability of KB195 in subjects with a UCD<br>• Determine the proportion of fasting plasma ammonia concentrations above the upper limit of normal (ULN) before and at the end of treatment<br>• Evaluate the effect of concomitant KB195 administration on indicators of nitrogen binding therapy (NBT) delivery and activity, as applicable, in the subset of subjects whose standard of care (SOC) includes NBT;Primary end point(s): Proportion of patients who achieve a =15% reduction from baseline in fasting plasma ammonia at the end of treatment;Timepoint(s) of evaluation of this end point: Day -1, Day 55 ± 1d