Chemoprotection effects to induce cell cycle arrest in human bone marrow
Conditions
Interventions
ALRN-6924 or 250 mL of 0.9% NaCl solution.
Sponsors
Aileron Therapeutics Inc.
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: Is healthy, defined as being free from clinically significant (and clinically relevant per Principal Investigator) illness or disease as determined by their medical history, medical assessment, physical examination, clinical laboratory tests, and 12-lead ECG obtained during Screening and predose on Day 1. Is male or female, aged 18-65 years, inclusive, at the time of informed consent (except for cohorts of subjects undergoing scalp biopsy who will be females aged 18-60 years). Has a BMI ranging between 18.0 and 30.0 kg/m2, inclusive, at Screening. Has negative urine drug and cotinine screen results at Screening and predose on Day 1.
Exclusion criteria
Exclusion criteria: Has resting systolic blood pressure =140 mmHg and a resting diastolic blood pressure =90 mmHg at Screening. Has resting pulse =100 bpm at Screening. Has QTc intervals corrected for heart rate via the Fridericia method (QTcF) >450 msec (males) and >480 msec (females) at Screening. Is pregnant or a nursing female.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Optimal cell cycle arrest defined as the lowest proportion of S-phase cells in the presence of the lowest rate of apoptosis in bone marrow cells using flow cytometry, or optimal cell cycle arrest defined as >2-fold induction of p21 over baseline in bone marrow cells using immuno-histochemistry (IHC) | — |
Secondary
| Measure | Time frame |
|---|---|
| Time to onset of cell cycle arrest in the bone marrow following administration of a single dose of ALRN-6924. Percent reduction in S-phase cells in the bone marrow following administration of a single dose of ALRN-6924. Duration of cell cycle arrest in the bone marrow following administration of a single dose of ALRN-6924. Pharmacodynamic response (time to onset of cell cycle arrest, percent reduction in S-phase cells, and duration of cell cycle arrest) in the bone marrow following slow bolus injection compared to IV infusion of a single dose of ALRN-6924. Determination of ALRN-6924 repeated dosing schedule for inducing and maintaining prolonged (0h-72h) cell cycle arrest in the bone marrow. PK parameters (eg, AUC, Cmax, tmax, t1/2) of ALRN-6924. Proportion of subjects with NCI CTCAE Grade 1/2 TEAEs. | — |
Countries
Netherlands
Outcome results
None listed