A Study of AK117 in Combination With Azacitidine in Patients With Myelodysplastic Syndromes

Akeso

Status and phase: Enrolling; Phase 2

Conditions: Higher-risk Myelodysplastic Syndromes

Treatments: Drug: AK117; Drug: Azacitidine; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT06196203

AK117-205

Details and patient eligibility

About

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).

Enrollment: 90 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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90 participants in 3 patient groups, including a placebo group

AK117 (dose 1) in combination with azacitidine

Experimental group

Description:

Subjects receive AK117 (dose 1) intravenously, in combination with azacitidine (75 mg/m2, D1-7, Q4W) subcutaneously

Treatment:

Drug: Azacitidine

Drug: AK117

AK117 (dose 2) in combination with azacitidine

Experimental group

Description:

Subjects receive AK117 (dose 2) intravenously, in combination with azacitidine (75 mg/m2, D1-7, Q4W) subcutaneously

Treatment:

Drug: Azacitidine

Drug: AK117

Placebo in combination with azacitidine

Placebo Comparator group

Description:

Subjects receive placebo intravenously, in combination with azacitidine (75 mg/m2, D1-7, Q4W) subcutaneously

Treatment:

Drug: Placebo

Drug: Azacitidine