KRRO-121 for hyperammonemia in urea cycle disorders: a first-in-human study

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

KRRO-121 is a GalNAc-conjugated RNA editing oligonucleotide intended to induce a de novo glutamine synthetase protein to improve ammonia clearance in people with urea cycle disorders. The trial is a first-in-human, randomized, placebo-controlled study with two parts: Phase 1 in healthy volunteers to assess safety, pharmacokinetics, and tolerability, and Phase 2 in patients with urea cycle disorders to evaluate safety and biological effects. Utilizing Korro Bio's OPERA platform, the approach aims to provide a pan-UCD therapeutic strategy independent of specific genetic mutations. The study will escalate doses to determine safety and tolerability, with ongoing monitoring by investigators and sponsor medical monitors. Primary objectives focus on safety and tolerability across cohorts, with pharmacokinetics and preliminary pharmacodynamic signals as secondary considerations.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* Adult male or female participants, 18 to 65 years of age
* Healthy as determined by medical history, physical examination, vital signs, 12-lead electrocardiogram (ECG), and screening laboratory assessments, in the opinion of the Investigator.
* Female participant of childbearing potential or male participant that is willing to use an approved, reliable means of contraception
* Willing and able to provide signed written informed consent and to comply with all study requirements

Exclusion Criteria:

* Any medical history that is clinically significant in the opinion of the Principal Investigator and Sponsor Medical Monitor
* Any laboratory value at screening or predose on Day -1 outside the local laboratory reference range that is clinically significant in the opinion of the Principal Investigator and Sponsor Medical Monitor
* Evidence of active systemic infection at Screening or Day 1 requiring antimicrobial, antiviral, or antifungal therapy
* Use of any investigational drug or device within 3 months or 5 half-lives (whichever is longer) prior to Day 1
* Concurrent participation in any other interventional clinical study

Where it's running

• Nucleus Network Pty Ltd
  Melbourne, Victoria, Australia Recruiting

Study contacts

• Study coordinator: Nucleus Network Pty Ltd Study Director
• Email: name@name.com
• Phone: (03) 8593 9801

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• LNP.UCD.ABE for severe urea cycle disorders in young children

  This trial tests a single IV dose of LNP.UCD.ABE in five young children with severe urea cycle disorders to see if it is safe and may help reduce ammonia buildup.

  Recruiting Phase 1/2 Children's Hospital of Philadelphia · Philadelphia, Pennsylvania · NCT07667387

• Home Ammonia Monitoring for People with Metabolic Ammonia Disorders

  This study tests whether people with certain ammonia metabolism disorders can successfully measure their ammonia levels at home every day.

  Recruiting Sequitur Health Corp. · Portland, Oregon · NCT06953505

• Glycerol phenylbutyrate for Chinese children and teens with urea cycle disorders

  This project will try glycerol phenylbutyrate in children and teens in China who have urea cycle disorders to see if it lowers ammonia and reduces hyperammonemic crises over five years.

  Recruiting at 5 sites Tongji Hospital · Beijing, Beijing Municipality and 4 other locations · NCT06904027

• Long-term follow-up for participants in an iECURE protocol

  This study looks at the long-term safety and effectiveness of a treatment for people who have already been part of an earlier study, while also tracking the health of those who didn’t receive the treatment.

  Recruiting at 4 sites iECURE, Inc. · Aurora, Colorado and 3 other locations · NCT06805695

• Analyzing urea production in healthy individuals and patients with urea cycle disorders

  This study is testing how well the body makes urea in healthy people and those with urea cycle disorders to better understand these conditions and improve treatments.

  Recruiting University Children's Hospital, Zurich · Zurich, Canton of Zurich · NCT05671666

• Evaluating liver tissue in patients with urea cycle disorders

  This study looks at liver tissue from people with urea cycle disorders to see how these conditions affect the liver, especially in those who have had a liver transplant or biopsy.

  Recruiting Baylor College of Medicine · Washington D.C., District of Columbia and 1 other locations · NCT04908319

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.