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

Phase 2Not Yet RecruitingNCT07773246

Korro Bio, Inc.30 enrolled

Overview

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.

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Urea Cycle Disorders, Inborn

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: 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),

Time frame: Day 1 through Day 50

Secondary Outcomes

Maximum blood concentration (Cmax)

Maximum blood concentration (Cmax) of KRRO-121

Time frame: Day 1 to Day 50