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

A Randomized, Double-blind, Placebo-controlled, Multicenter Phase 2 Study of AK117/Placebo in Combination With Azacitidine in Patients With Newly Diagnosed Higher-risk Myelodysplastic Syndromes

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).

Study Overview

• Status: Recruiting
• Conditions: Higher-risk Myelodysplastic Syndromes
• Intervention / Treatment: Drug: AK117; Drug: Azacitidine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jie Yang, MD; Phone Number: +86(0760)89873999; Email: clinicaltrials@akesobio.com

Study Locations

• China
  • Tianjin, China
    • Recruiting
    • Institute of hematolongy&blood diseases hospital, chinese academy of medical sciences&peking union medical college
    • Contact: Zhijian Xiao
• United States
  • Florida
    • Orange City, Florida, United States, 32763
      • Recruiting
      • Mid Florida Hematology and Oncology Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AK117 (dose 1) in combination with azacitidine; Subjects receive AK117 (dose 1) intravenously, in combination with azacitidine (75 mg/m2, D1-7, Q4W) subcutaneously	Drug: AK117; AK117 IV injection; Drug: Azacitidine; Azacitidine SC injection
Experimental: AK117 (dose 2) in combination with azacitidine; Subjects receive AK117 (dose 2) intravenously, in combination with azacitidine (75 mg/m2, D1-7, Q4W) subcutaneously	Drug: AK117; AK117 IV injection; Drug: Azacitidine; Azacitidine SC injection
Placebo Comparator: Placebo in combination with azacitidine; Subjects receive placebo intravenously, in combination with azacitidine (75 mg/m2, D1-7, Q4W) subcutaneously	Drug: Azacitidine; Azacitidine SC injection; Drug: Placebo; Placebo IV injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete remission rate (CRR)	CRR is defined as the proportion of subjects with complete remission (CR) per International Working Group (IWG) 2023 criteria	Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)	The proportion of subjects with recorded response per IWG 2023	Up to approximately 2 years
Time to response (TTR)	Time from the randomization to the first recorded response	Up to approximately 2 years
Time to CR (TTCR)	Time from the randomization to the first recorded CR	Up to approximately 2 years
Duration of response (DoR)	Time from the first recorded response until disease relapse or progression or death due to any cause, whichever occurs first	Up to approximately 2 years
Duration of CR (DoCR)	Time from the first recorded CR until disease relapse or progression or death due to any cause, whichever occurs first	Up to approximately 2 years
Event-free survival (EFS)	Time from randomization until transformation to AML or death due to any cause, whichever occurs first	Up to approximately 2 years
Overall survival (OS)	The time from randomization until death due to any cause	Up to approximately 2 years
Number of subjects with adverse events (AEs)	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	Up to approximately 2 years
Pharmacokinetic characteristics	Serum concentrations of AK117 in individual subjects at different time points after AK117 administration	Up to approximately 2 years
Anti-drug antibody (ADA)	Number of subjects with detectable anti-drug antibodies	Up to approximately 2 years

Collaborators and Investigators

• Sponsor: Akeso

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2024
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: December 24, 2023
• First Submitted That Met QC Criteria: December 24, 2023
• First Posted (Actual): January 9, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2024
• Last Update Submitted That Met QC Criteria: March 22, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Azacitidine
• Other Study ID Numbers: AK117-205

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No