Clinical trial NCT04900350: A Trial of AK117 (Anti-CD47) in Patients With Myelodysplastic Syndrome
Official title: A Phase I/II Trial of AK117 (Anti-CD47) in Patients With Higher-risk Myelodysplastic Syndrome
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Myelodysplastic Syndrome
Lead sponsor: Akeso
Sponsor class: INDUSTRY
First posted: 2021-05-25
Enrollment: 136
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a open label, phase I/II study. All patients are diagnosed with higher-risk MDS, Eastern Cooperative Oncology Group (ECOG) performance status 0-2. The purpose of this study is to evaluate the safety and efficacy of AK117 + azacitidine in subjects with higher-risk MDS.


Eligibility criteria: Inclusion Criteria:

* Age ≥18 years (at the time consent is obtained).
* Be able and willing to provide written informed consent and to comply with all requirements of study participation (including all study procedures).
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2.
* Has a life expectancy of at least 12 weeks.
* Phase 1: Diagnosis of higher-risk MDS that is either previously untreated or relapsed/refractory.
* Phase 2: Diagnosis of higher-risk MDS that is previously untreated.
* White blood cell count ≤ 25 x 10\^9/L (hydroxyurea may be used to reduce the WBC count).
* Has adequate organ function.
* All female and male subjects of reproductive potential must agree to use an effective method of contraception, as determined by the Investigator, during and for 120 days after the last dose of study treatment.

Exclusion Criteria:

* Is currently participating in a study of an investigational agent or using an investigational device.
* Has undergone major surgery within 30 days of Study Day 1.
* Has a known additional malignancy that is progressing or requires systemic treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
* Previous allogeneic hematopoietic stem cell transplant (allo-HSCT) .
* Prior treatment with any anti-CD47 or anti-SIRPα (signal regulatory protein alpha) agent.
* Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
* Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected).
* History of myocardial infarction, unstable angina, congestive heart failure within 12 months prior to day 1 of study treatment.
* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of this subject to participate, in the opinion of the treating investigator.
* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
* Has received a live virus vaccine within 30 days of the planned first dose of study therapy.
* Is pregnant, breastfeeding, or expecting to conceive or father a child within the projected duration of the study including 120 days following the last dose of study treatment.
* Has any concurrent medical condition that, in the opinion of the Investigator, would complicate or compromise compliance with the study or the well-being of the subject.

Primary outcomes:
measure: Rate of Complete Remission (CR)
timeFrame: Approximately 6 months
measure: Number of participants with adverse events (AEs)
timeFrame: Up to approximately 2 years.
measure: Duration of Complete Remission (DoCR)
timeFrame: Up to approximately 2 years.
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 2 years.
measure: Duration of Response (DOR)
timeFrame: Up to approximately 2 years.
measure: Progression Free Survival (PFS)
timeFrame: Up to approximately 2 years.
measure: Maximum observed concentration (Cmax) of AK117
timeFrame: Up to 2 years.
measure: Anti-drug antibodies (ADA)
timeFrame: Up to 2 years.
Other outcomes:
Locations:
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital of Soochow University
name: Depei Wu, MD
role: PRINCIPAL_INVESTIGATOR
References: