The study was terminated for business decision reasons.

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).

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