NCT07773246

Brief Summary

Phase 1/2 Study of KRRO-121 is a randomized, placebo-controlled study in Healthy Volunteers (Phase 1 SAD and MAD) and Study Participants with Urea Cycle Disorders (Phase 2). The primary objective of the study is to evaluate the safety of KRRO-121.

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at P25-P50 for phase_1

Timeline
11mo left

Started Sep 2026

Geographic Reach
1 country

1 active site

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress9%
Sep 2026Sep 2027

First Submitted

Initial submission to the registry

August 14, 2026

Completed
5 days until next milestone

First Posted

Study publicly available on registry

August 19, 2026

Completed
13 days until next milestone

Study Start

First participant enrolled

September 1, 2026

Completed
11 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2027

Expected
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2027

Last Updated

August 20, 2026

Status Verified

August 1, 2026

Enrollment Period

11 months

First QC Date

August 14, 2026

Last Update Submit

August 18, 2026

Conditions

Urea Cycle Disorders, InbornUrea Cycle DisordersOrnithine Transcarbamylase (OTC) DeficiencyArginase 1 DeficiencyNAGS DeficiencyCarbamylphosphate Synthetase IOrnithine Transporter Mitochondrial 1Argininosuccinate SynthaseArgininosuccinate Lyase DeficiencyN-acetyl Glutamate - SynthetaseCitrin Deficiency

Keywords

KRRO-121stabilized variant of glutamine synthetase (GS)ammonia clearanceRNA-editing

Outcome Measures

Primary Outcomes (2)

  • Incidence of dose limiting toxicities (DLT) (Safety and Tolerability)

    General toxicity: Any Grade 3 or higher adverse event (AE) per Common Terminology Criteria for Adverse Events (CTCAE); Serious adverse events: Any serious adverse event (SAE) assessed as related or possibly related to KRRO-121.

    Day 1 through 14 days post-dose

  • Frequency and severity of treatment-emergent adverse events (TEAEs; per Common Terminology Criteria for Adverse Events [CTCAE]) (Safety and Tolerability)

    Any adverse event (AE) per Common Terminology Criteria for Adverse Events (CTCAE),

    Day 1 through Day 50

Secondary Outcomes (1)

  • Maximum blood concentration (Cmax)

    Day 1 to Day 50

Study Arms (2)

KRRO-121

EXPERIMENTAL

KRRO-121 is a GalNAc-conjugated RNA-editing oligonucleotide that recruits endogenous hepatic ADAR to edit mRNA, producing a de novo glutamine synthetase (GS) protein resistant to feedback-driven proteasomal degradation. By stabilizing hepatic GS, KRRO-121 augments ammonia clearance capacity independently of the underlying urea cycle enzyme defect.

Drug: KRRO-121

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

KRRO-121DRUG

KRRO-121, subcutaneous injection

KRRO-121
PlaceboDRUG

Placebo, subcutaneous injection

Placebo

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Nucleus Network Pty Ltd

Melbourne, Victoria, 3004, Australia

Location

MeSH Terms

Conditions

Urea Cycle Disorders, InbornOrnithine Carbamoyltransferase Deficiency DiseaseHyperargininemiaN-acetyl glutamate synthetase deficiencyArgininosuccinic AciduriaAdult-onset citrullinemia type 2

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, InbornBrain Diseases, MetabolicBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesAmino Acid Metabolism, Inborn ErrorsMetabolism, Inborn ErrorsGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesMetabolic DiseasesNutritional and Metabolic DiseasesGenetic Diseases, X-Linked

Central Study Contacts

Nucleus Network Pty Ltd Study Director

CONTACT

(03) 8593 9801name@name.com

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Masking Details
Sponsor study team
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Model Details: Placebo-controlled dose escalation
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 14, 2026

First Posted

August 19, 2026

Study Start

September 1, 2026

Primary Completion (Estimated)

August 1, 2027

Study Completion (Estimated)

September 1, 2027

Last Updated

August 20, 2026

Record last verified: 2026-08

Locations

AU(1)