Clinical trial NCT06677307: A Phase 1/2a, Single- and Multiple-dose Escalation Study of KRRO-110
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Alpha-1 Anti-trypsin Deficiency
AATD
Lead sponsor: Korro Bio, Inc.
Sponsor class: INDUSTRY
First posted: 2024-11-06
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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 \< 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

Primary outcomes:
measure: Safety and Tolerability
timeFrame: From Day 1 to Day 43 in the SAD and from Day 1 to Day 85 in the MAD
Secondary outcomes:
measure: Pharmacokinetics (PK) of KRRO-110
timeFrame: Day 1 to Day 43 (SAD), and Day 1 to Day 85 (MAD)
measure: Pharmacodynamics (PD) of KRRO-110
timeFrame: Day 1 to Day 43 (SAD), and Day 1 to Day 85 (MAD)
measure: Pharmacokinetics (PK) of KRRO-110
timeFrame: Day 1 to Day 43 (SAD), and Day 1 to Day 85 (MAD)
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Nucleus Network Pty Ltd
state: Victoria
city: Auckland
country: New Zealand
facility: New Zealand Clinical Research
city: Christchurch
country: New Zealand
facility: New Zealand Clinical Research
Study officials:
affiliation: Korro Bio, Inc.
name: Study Director
role: STUDY_DIRECTOR
References: