A Phase 1/2a, Single- and Multiple-dose Escalation Study of KRRO-110
- Registration Number
- NCT06677307
- Lead Sponsor
- Korro Bio, Inc.
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 64
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 (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 < 50%
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Arm 2: Placebo (Part A only) KRRO-110 Placebo, IV administration Arm 1: KRRO-110 (Part A and Part B) KRRO-110 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).
- Primary Outcome Measures
Name Time Method Safety and Tolerability From Day 1 to Day 43 in the SAD and from Day 1 to Day 85 in the MAD Type, frequency, and severity of treatment-emergent adverse events (TEAEs)
- Secondary Outcome Measures
Name Time Method Pharmacokinetics (PK) of KRRO-110 Day 1 to Day 43 (SAD), and Day 1 to Day 85 (MAD) PK profile of KRRO-110 half-life (t1/2), area under the concentration-time curve (AUC), and trough level (MAD cohorts only).
Pharmacodynamics (PD) of KRRO-110 Day 1 to Day 43 (SAD), and Day 1 to Day 85 (MAD) PD profile of KRRO-110 based on change from Baseline in alpha-antitrypsin (AAT) enzyme levels at all measured timepoints (PiZZ participants only).
Trial Locations
- Locations (2)
New Zealand Clinical Research
🇳🇿Christchurch, New Zealand
Nucleus Network Pty Ltd
🇦🇺Melbourne, Victoria, Australia