Phase 1/2 Study of KRRO-121 in Healthy Volunteers and Patients With UCD

A Phase 1/2, Randomized, Double-Blind, Placebo-Controlled, Single- and Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of KRRO-121 in Healthy Volunteers and Patients With Urea Cycle Disorders

Status

Not yet recruiting

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT07773246

Acronym

ANCHOR

Enrollment

Registered

2026-08-19

Start date

2026-09-01

Completion date

2027-09-01

Last updated

2026-08-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Arginase 1 Deficiency, Argininosuccinate Lyase Deficiency, Argininosuccinate Synthase, Carbamylphosphate Synthetase I, Citrin Deficiency, N-acetyl Glutamate - Synthetase, NAGS Deficiency, Ornithine Transcarbamylase (OTC) Deficiency, Ornithine Transporter Mitochondrial 1, Urea Cycle Disorders, Urea Cycle Disorders, Inborn

Keywords

KRRO-121, stabilized variant of glutamine synthetase (GS), ammonia clearance, RNA-editing

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.

Detailed description

KRRO-121 is a GalNAc-conjugated RNA editing oligonucleotide in development for the potential treatment of hyperammonemia in patients with UCDs. Utilizing Korro's proprietary OPERA® platform, KRRO-121 is designed to generate a stabilized, de novo glutamine synthetase (GS) protein, a critical enzyme involved in ammonia clearance. This synthetic rescue approach is designed to augment ammonia clearance in hyperammonemia-driven diseases such as UCDs. Korro's preclinical data support the potential for KRRO-121 to be a UCD treatment that may control ammonia levels independent of any mutational background (pan-UCD). The purpose of this first-in-human (FIH) study is to determine the safety and tolerability of escalating doses of KRRO-121, to evaluate the pharmacokinetics of KRRO-121, and to assess the effect of KRRO-121 in healthy volunteers and in study participants with UCD. The study name is ANCHOR: AssessmeNt of Control of Hyperammonemia through Oligonucleotide-based RNA editing

Interventions

DRUGKRRO-121

KRRO-121, subcutaneous injection

DRUGPlacebo

Placebo, subcutaneous injection

Study design

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Masking description

Sponsor study team

Intervention model description

Placebo-controlled dose escalation

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Yes

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

Design outcomes

Primary

Measure	Time frame	Description
Incidence of dose limiting toxicities (DLT) (Safety and Tolerability)	Day 1 through 14 days post-dose	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.
Frequency and severity of treatment-emergent adverse events (TEAEs; per Common Terminology Criteria for Adverse Events [CTCAE]) (Safety and Tolerability)	Day 1 through Day 50	Any adverse event (AE) per Common Terminology Criteria for Adverse Events (CTCAE),

Secondary

Measure	Time frame	Description
Maximum blood concentration (Cmax)	Day 1 to Day 50	Maximum blood concentration (Cmax) of KRRO-121

Countries

Australia

Contacts

CONTACTNucleus Network Pty Ltd Study Director

name@name.com(03) 8593 9801

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Aug 21, 2026