A Phase 1 Pharmacology Study of the Dual MDMX/MDM2 Inhibitor, ALRN-6924, in Healthy Volunteers.
- Conditions
- Chemoprotection effectsto induce cell cycle arrest in human bone marrow
- Registration Number
- NL-OMON52916
- Lead Sponsor
- Aileron Therapeutics Inc.
- Brief Summary
Trial ended prematurely
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 105
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.
Has resting systolic blood pressure <=90 or >=140 mmHg and a resting diastolic
blood pressure <=51 or >=90 mmHg at Screening.
Has resting pulse <=50 or >=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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Optimal cell cycle arrest defined as the lowest proportion of S-phase cells in<br /><br>the presence of the lowest rate of apoptosis in bone marrow cells using flow<br /><br>cytometry, or optimal cell cycle arrest defined as >2-fold induction of p21<br /><br>over baseline in bone marrow cells using immuno-histochemistry (IHC)</p><br>
- Secondary Outcome Measures
Name Time Method <p>Time to onset of cell cycle arrest in the bone marrow following administration<br /><br>of a single dose of ALRN-6924.<br /><br>Percent reduction in S-phase cells in the bone marrow following administration<br /><br>of a single dose of ALRN-6924.<br /><br>Duration of cell cycle arrest in the bone marrow following administration of a<br /><br>single dose of ALRN-6924.<br /><br>Pharmacodynamic response (time to onset of cell cycle arrest, percent reduction<br /><br>in S-phase cells, and duration of cell cycle arrest) in the bone marrow<br /><br>following slow bolus injection compared to IV infusion of a single dose of<br /><br>ALRN-6924.<br /><br>Determination of ALRN-6924 repeated dosing schedule for inducing and<br /><br>maintaining prolonged (0h-72h) cell cycle arrest in the bone marrow.<br /><br>PK parameters (eg, AUC, Cmax, tmax, t1/2) of ALRN-6924.<br /><br>Proportion of subjects with NCI CTCAE Grade 1/2 TEAEs.</p><br>