PrimaryTo determine the pharmacologically optimal dose of ALRN-6924 to induce transient cell cycle arrest in human bone marrow and other tissues.SecondaryTo characterize relative to ALRN-6924 administration the time to onset, the magnitude, and the…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Chemoprotection effects
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
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 outcome
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.
Background summary
ALRN-6924 is being developed by Aileron Therapeutics, Inc. (Aileron) as a
potential treatment for the supportive care of patients with TP53-mutant
tumors, but an intact p53 pathway in their non-malignant tissues.
Study objective
Primary
To determine the pharmacologically optimal dose of ALRN-6924 to induce
transient cell cycle arrest in human bone marrow and other tissues.
Secondary
To characterize relative to ALRN-6924 administration the time to onset, the
magnitude, and the duration of cell cycle arrest in human bone marrow
To characterize the pharmacodynamic characteristics of IV infusion vs slow
bolus injection of ALRN-6924
To evaluate schedules of repeated ALRN-6924 administration that will result in
prolonged (0h-72h) cell cycle arrest in human bone marrow
To evaluate the pharmacokinetic (PK) profile of ALRN-6924 following IV infusion
and slow bolus injection
Safety and tolerability of single and repeat doses of ALRN-6924 in healthy
volunteers
Study design
This is a Phase 1, open-label, single center clinical trial for evaluation of
ALRN-6924 pharmacological effects on human bone marrow in healthy volunteers.
The study will be conducted in 2 parts.
Intervention
ALRN-6924 or 250 mL of 0.9% NaCl solution.
Study burden and risks
Since the study is being executed in healthy volunteers, there are no
anticipated benefits of the IMP. Please see the IB for further
information.
Summer Street, Unit #101 285
Boston MA 02210
US
Summer Street, Unit #101 285
Boston MA 02210
US
Listed location countries
Age
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
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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-003178-34-NL |
| CCMO | NL74659.056.20 |