MDS, Myelodysplastic Syndromes
Conditions
Brief summary
Phase 1 study evaluating the safety and efficacy of APR-548 in combination with Azacitidine for the treatment of TP53-Mutant Myelodysplastic Syndromes.
Detailed description
Open-label first-in-human (FIH) phase 1 clinical trial assessing the safety, pharmacokinetics (PK), and clinical activity of orally (p.o.) administered APR-548 alone and in combination with azacitidine for the treatment of TP53-mutant myelodysplastic syndromes (MDS).
Interventions
DRUGAPR-548 + Azacitidine
APR-548 monotherapy period followed by APR-548 in combination with Azacitidine
Sponsors
Aprea Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Provision of signed and dated, written informed consent prior to any study specific procedures. 2. Documented diagnosis of TP53-mutant MDS, according to WHO criteria that is relapsed/refractory or previously untreated MDS. 3. Adequate organ function as defined by the following laboratory values: 1. Creatinine clearance ≥60 mL/min (by Cockcroft-Gault method, Appendix I), 2. Total serum bilirubin ≤1.5 × upper limit of normal (ULN) unless due to Gilbert's syndrome or MDS organ involvement, 3. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN, unless due to MDS organ involvement. 4. Age ≥18 years at the time of signing the informed consent form. 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 (Appendix II). 6. Projected life expectancy of ≥12 weeks. 7. Clear ocular media and adequate pupil dilation to permit fundus examination and retinal imaging.
Exclusion criteria
1. Cardiac abnormalities, which includes, but not limited to: 1. Myocardial infarction within six months prior to enrollment 2. New York Heart Association Class III or IV heart failure or known LVEF \<40% 2. Concomitant malignancies or previous malignancies with less than a 1 year disease-free interval at the time of signing informed consent. 3. Use of cytotoxic chemotherapeutic agents, or experimental agents for the treatment of MDS within 14 days or 5 half-lives of the product (whichever is shorter) of the first day of study drug treatment. 4. Prior exposure to eprenetapopt (APR-246). 5. A female subject who is pregnant or breast-feeding. 6. Known history of human immunodeficiency virus (HIV), active hepatitis B or active hepatitis C infection. 7. Malabsorption syndrome or other condition likely to affect gastrointestinal absorption of APR-548. 8. Known history or current evidence of ocular disease in either eye
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Investigate the Number of Participants With Treatment Emergent Adverse Events From Treatment With APR-548 as Monotherapy and in Combination With Azacitidine | Through study completion, approximately 28 days | Occurrence of frequency of treatment emergent adverse events by reviewing safety data including AEs, vital signs, laboratory data, ECG, ophthalmologic assessment findings, and other physical exam findings. |
Countries
United States
Participant flow
Recruitment details
Study was terminated prior to enrollment into cohort 2 and 3.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Dose level 1
APR-548 + Azacitidine: APR-548 monotherapy period followed by APR-548 in combination with Azacitidine | 4 |
| Cohort 2 Dose level 2
APR-548 + Azacitidine: APR-548 monotherapy period followed by APR-548 in combination with Azacitidine | 0 |
| Cohort 3 Dose level 3
APR-548 + Azacitidine: APR-548 monotherapy period followed by APR-548 in combination with Azacitidine | 0 |
| Total | 4 |
Baseline characteristics
| Characteristic | Total | Cohort 1 | Cohort 3 | Cohort 2 |
|---|---|---|---|---|
| Age, Continuous | 64 years | 64 years | — | — |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | — | — |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | — | — |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | — | — |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | — | — |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | — | — |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | — | — |
| Race (NIH/OMB) White | 4 Participants | 4 Participants | — | — |
| Region of Enrollment United States | 4 participants | 4 participants | — | — |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 4 |
| other Total, other adverse events | 2 / 4 |
| serious Total, serious adverse events | 2 / 4 |
Outcome results
Primary
To Investigate the Number of Participants With Treatment Emergent Adverse Events From Treatment With APR-548 as Monotherapy and in Combination With Azacitidine
Occurrence of frequency of treatment emergent adverse events by reviewing safety data including AEs, vital signs, laboratory data, ECG, ophthalmologic assessment findings, and other physical exam findings.
Time frame: Through study completion, approximately 28 days
Population: Study was terminated.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 | To Investigate the Number of Participants With Treatment Emergent Adverse Events From Treatment With APR-548 as Monotherapy and in Combination With Azacitidine | 3 Participants |