Higher-risk Myelodysplastic Syndromes
Conditions
Brief summary
This is a Phase 2 randomized, double-blind, placebo-controlled, multicenter study evaluating the efficacy and safety of AK117 or placebo, combined with azacitidine in patients with newly diagnosed higher-risk myelodysplastic syndromes (HR-MDS).
Interventions
Sponsors
Akeso
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years old at the time of enrolment. * Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2. * Expected life expectancy ≥ 3 months. * Newly diagnosed HR-MDS, according to the 2016 World Health Organization (WHO) classification with the presence of \< 20% blasts in bone marrow or peripheral blood; Overall IPSS-R score ≥ 3.5. * Ability to undergo the study-required bone marrow sample collection procedures. * Suitable venous access for the study-required blood sampling (i.e., including PK and immunogenicity). * Female patients of childbearing age must have negative serum pregnancy test results before randomization or per region-specific guidance documented in the informed consent and a negative urine pregnancy test on the day of first dose prior to dosing. * Female patients of childbearing potential having sex with an unsterilized male partner must agree to use a highly effective method of contraception from the beginning of screening until 180 days after the last dose of the study treatment. * Unsterilized male patients having sex with a female partner of childbearing potential must agree to use an effective method of contraception from the beginning of screening until 180 days after the last dose of study treatment.
Exclusion criteria
* MDS evolving from a pre-existing myeloproliferative neoplasm (MPN), myelodysplastic/myeloproliferative neoplasms (MDS/MPN). * Prior treatment with Cluster of Differentiation (CD) 47 or Signal-regulatory protein alpha (SIRPα)-targeting agents. * Concurrently participating in another interventional clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study. * Patients who previously diagnosed with another malignancy and have any evidence of residual disease. * Known allergy to any component of any study drug; known history of severe hypersensitivity to other monoclonal antibodies. * Patients with any psychiatric or social factor which the investigator deems may interfere with the patient's ability to comply with the requirements of the study. * Patients with current hypertension with systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg after oral antihypertensive therapy. * Patients with known cardiopulmonary disease defined as unstable angina, clinically significant arrhythmia, congestive heart failure (New York Heart Association Class III or IV), decompensated cirrhosis, nephrotic syndrome, uncontrolled metabolic disorders. * Patients who are breastfeeding or plans to breastfeed during the study. * Other conditions where the investigator considers the patient inappropriate for enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete remission rate (CRR) | Up to approximately 2 years | CRR is defined as the proportion of subjects with complete remission (CR) per International Working Group (IWG) 2023 criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to response (TTR) | Up to approximately 2 years | Time from the randomization to the first recorded response |
| Time to CR (TTCR) | Up to approximately 2 years | Time from the randomization to the first recorded CR |
| Duration of response (DoR) | Up to approximately 2 years | Time from the first recorded response until disease relapse or progression or death due to any cause, whichever occurs first |
| Duration of CR (DoCR) | Up to approximately 2 years | Time from the first recorded CR until disease relapse or progression or death due to any cause, whichever occurs first |
| Overall response rate (ORR) | Up to approximately 2 years | The proportion of subjects with recorded response per IWG 2023 |
| Overall survival (OS) | Up to approximately 2 years | The time from randomization until death due to any cause |
| Number of subjects with adverse events (AEs) | Up to approximately 2 years | An AE is any untoward medical occurrence in a subject, temporally associated with the use of study treatment, whether or not considered related to the study treatment |
| Pharmacokinetic characteristics | Up to approximately 2 years | Serum concentrations of AK117 in individual subjects at different time points after AK117 administration |
| Anti-drug antibody (ADA) | Up to approximately 2 years | Number of subjects with detectable anti-drug antibodies |
| Event-free survival (EFS) | Up to approximately 2 years | Time from randomization until transformation to AML or death due to any cause, whichever occurs first |
Countries
China, United States
Contacts
Primary ContactWenting Li, MD
Outcome results
None listed