NCT06677307TerminatedPhase 1
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)
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- Korro Bio, Inc.
- Enrollment
- 42
- Locations
- 7
- Primary Endpoint
- Safety and Tolerability
Study Overview
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).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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
Arms & Interventions
Arm 2: Placebo (Part A only)
Placebo Comparator
Placebo, IV administration
Intervention: KRRO-110 (Drug)
Arm 1: KRRO-110 (Part A and Part B)
Experimental
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).
Intervention: KRRO-110 (Drug)
Outcomes
Primary Outcomes
Safety and Tolerability
Time Frame: 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 Outcomes
- Pharmacodynamics (PD) of KRRO-110(Day 1 to Day 43 (SAD), and Day 1 to Day 85 (MAD))
- Pharmacokinetics (PK) of KRRO-110(Day 1 to Day 43 (SAD), and Day 1 to Day 85 (MAD))
Investigators
Study Sites (7)
Loading locations...
Similar Trials
Active, not recruiting
Phase 1
BOXR1030 T Cells in Subjects With Advanced GPC3-Positive Solid TumorsSquamous Cell Carcinoma of the LungMyxoid/Round Cell LiposarcomaHepatocellular CarcinomaMerkel Cell CarcinomaNCT05120271Sotio Biotech Inc.7
Completed
Phase 1
Phase 1 Safety, Tolerability, PK & PD Study of AD-214 Administered to Healthy VolunteersInterstitial Lung DiseaseNCT04415671AdAlta Limited50
Recruiting
Phase 1
A Phase 1/2 Study of D3S-002 as Monotherapy or Combination Therapy in Adult Subjects With Advanced Solid Tumors With MAPK Pathway MutationsAdvanced Solid Tumors With MAPK Pathway MutationsNCT05886920D3 Bio (Wuxi) Co., Ltd67
Active, not recruiting
Phase 1
Phase 1 Study of OLX-07010 in Healthy Adult and Elderly ParticipantsAlzheimer DiseaseNCT05696483Oligomerix, Inc76
Completed
Phase 1
A Study of Anti-VEGFR2 AK109 in Subjects With Advanced Solid TumorsSolid TumorNCT04547205Akeso40