A Phase 1/2a, Single- and Multiple-dose Escalation Study of KRRO-110 (REWRITE)

A Phase 1/2a, Single- and Multiple-dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of KRRO 110 in Healthy Adult Volunteers and in Adult Participants With Alpha-1 Antitrypsin Deficiency (AATD) (REWRITE)

The purpose of this first-in human (FIH) study is to assess the safety, tolerability, and pharmacokinetics (PK) of single and multiple doses of KRRO-110 in both healthy adult participants and in clinically stable patients with Alpha-1 antitrypsin deficiency (AATD).

Study Overview

• Status: Terminated
• Conditions: AATD; Alpha-1 Anti-trypsin Deficiency
• Intervention / Treatment: Drug: KRRO-110

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Brisbane, Queensland, Australia, 4032
      • The Prince Charles Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3065
      • St. Vincent's Hospital Melbourne
    • Melbourne, Victoria, Australia, 3004
      • Nucleus Network Pty Ltd
• New Zealand
  • Auckland, New Zealand
    • New Zealand Clinical Research
  • Christchurch, New Zealand
    • New Zealand Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Part A SAD cohort Inclusion Criteria (Healthy Volunteers)

• Adult male or female participants, 18 to 65 years of age
• Documented PiMM genotype
• Participants who are willing to and able to provide signed written informed consent

PiZZ Genotype (Part A SAD and Part B MAD cohorts) Inclusion Criteria (PiZZ Genotype)

• Adult male or female participants 18 to 70 years of age (inclusive)
• Documented PiZZ genotype
• Baseline blood total AAT level < 11 µM/L

Exclusion Criteria:

Exclusion Criteria (Healthy Volunteers)

• Female participant of childbearing potential or male participant that is unable or unwilling to use an approved, reliable means of contraception
• Body mass index (BMI) > 32 or < 18.5 kg/m2
• History or current clinical evidence of hepatic disease
• Evidence of active infection
• History of medical condition(s), eg, advance cardiac disease, current or recent malignancy, organ transplantation, or other illness
• Serology result indicative of any exposure (past or active) to hepatitis C, hepatitis B, or human immunodeficiency virus (HIV)
• Respiratory or other acute illness within 8 weeks
• Tobacco use of any kind within 6 months

Exclusion Criteria (PiZZ Genotype)

• Female participant of childbearing potential or male participant that is unable or unwilling to use an approved, reliable means of contraception
• BMI > 32 or < 18.5 kg/m2 or weight > 90 kg
• History of FEV1 < 35%
• History or current clinical evidence of advanced hepatic disease and/or pulmonary disease
• Use of an experimental therapy except KRRO-110 within 6 months or 5 half-lives for the experimental therapy, whichever is greater
• Tobacco use of any kind within 6 months
• Use of conventionally dosed AAT augmentation therapy within 5 half-lives
• Serology result consistent with exposure to HIV, or serology consistent with active hepatitis B or hepatitis C infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: KRRO-110 (Part A and Part B); KRRO-110 is an RNA editing oligonucleotide encapsulated in a lipid nanoparticle (LNP) administered by intravenous (IV) infusion as a single dose in Part A (SAD), multi-dose in Part B (MAD).	Drug: KRRO-110; KRRO-110 drug product, IV
Placebo Comparator: Arm 2: Placebo (Part A only); Placebo, IV administration	Drug: KRRO-110; KRRO-110 drug product, IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability	Type, frequency, and severity of treatment-emergent adverse events (TEAEs)	From Day 1 to Day 43 in the SAD and from Day 1 to Day 85 in the MAD

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK) of KRRO-110	PK profile of KRRO-110 including maximum blood concentration (Cmax)	Day 1 to Day 43 (SAD), and Day 1 to Day 85 (MAD)
Pharmacodynamics (PD) of KRRO-110	PD profile of KRRO-110 based on change from Baseline in alpha-antitrypsin (AAT) enzyme levels at all measured timepoints (PiZZ participants only).	Day 1 to Day 43 (SAD), and Day 1 to Day 85 (MAD)
Pharmacokinetics (PK) of KRRO-110	PK profile of KRRO-110 half-life (t1/2), area under the concentration-time curve (AUC), and trough level (MAD cohorts only).	Day 1 to Day 43 (SAD), and Day 1 to Day 85 (MAD)

Collaborators and Investigators

• Sponsor: Korro Bio, Inc.
• Investigators: Study Director: Study Director, Korro Bio, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2025
• Primary Completion (Actual): October 31, 2025
• Study Completion (Actual): December 15, 2025

Study Registration Dates

• First Submitted: November 4, 2024
• First Submitted That Met QC Criteria: November 5, 2024
• First Posted (Actual): November 6, 2024

Study Record Updates

• Last Update Posted (Actual): April 17, 2026
• Last Update Submitted That Met QC Criteria: April 14, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Genetic Diseases, Inborn; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Liver Diseases; Subcutaneous Emphysema; Emphysema; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; alpha 1-Antitrypsin Deficiency
• Other Study ID Numbers: KRRO-110-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No