A Safety Study of SYNT001 in Subjects With Chronic, Stable Warm Autoimmune Hemolytic Anemia (WAIHA)

Overview

About this study

This study is being conducted to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and effects on warm autoimmune hemolytic anemia (WAIHA) disease activity markers of intravenous (IV) SYNT001.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Please contact the study team to discuss whether or not you are eligible to participate in a study.

Inclusion Criteria:

Subjects must meet the following criteria to be included:

  • Willing and able to read, understand and sign an informed consent form.
  • Male or female ≥18 years of age at the time of screening.
  • Confirmed diagnosis by enrolling physician of WAIHA, including positive direct Coombs test.
  • Hemoglobin <11 g/dL.
  • Evidence of active hemolysis including any one of the below:
    • LDH >upper limit of normal (ULN); or
    • Haptoglobin
    • Indirect bilirubin >ULN.
  • Other treatments for WAIHA:
    • If treated with rituximab or other anti-CD20 mAb, last dose >3 months prior to screening (a dose is defined as ≥10% of the intended dose);
    • If being treated with other immunosuppressants (ie, azathioprine, mycophenolate mofetil, methotrexate, cyclosporine, tacrolimus, sirolimus, or low-dose oral cyclophosphamide [≤100 mg/day]), dose must be stable (<25% change in dose) for the 4 weeks prior to screening;
    • If being treated with corticosteroids, dose must be ≤1mg/kg/day of prednisone or equivalent, and the dose may not be increased by more than 50% in the 2 weeks prior to screening;
    • No pulse corticosteroids are allowed in the 2 weeks prior to screening.
  • Treatment of chronic lymphocyte leukemia (CLL) or non-Hodgkin lymphoma (NHL) must be:
    • FDA-approved for oral treatment; and
    • Stable (<10% change in dose) for 6 weeks prior to screening; Bruton’s tyrosine kinase inhibitor dose must be stable (<10% change in dose) for 8 weeks prior to screening.
  • Body mass index (BMI) >18.5 kg/m2.
  • Has a negative pregnancy test (for women of childbearing potential) documented prior to the first dose of study drug.
  • Females of childbearing potential must agree to be abstinent or else use any two of the following medically acceptable forms of contraception (<1% per year failure rate) from the screening period through the final study visit: oral contraceptive, condom with or without spermicidal jelly, diaphragm or cervical cap with spermicidal jelly, or intra-uterine device (IUD). A female whose male partner has had a vasectomy must agree to use one additional form of medically acceptable contraception.
  • Females of non-childbearing potential, defined as surgically sterile (status post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or post-menopausal for at least 12 months do not require contraception during the study.
  • Males with female partners of childbearing potential, including males who are surgically sterile (post vasectomy), must agree to be abstinent or else use a medically acceptable form of contraception from the screening period through the final study visit.

Exclusion Criteria:

Subjects meeting any of the following criteria are to be excluded:

  • Subject unable or unwilling to comply with the protocol.
  • Active non-hematologic malignancy or history of non-hematologic malignancy in the 3 years prior to screening (exclusive of non-melanoma skin cancer and cervical cancer in situ).
  • Karnofsky Performance Scale ≤50.
  • Estimated glomerular filtration rate (eGFR) <45 mL/minute/1.73m2.
  • Platelet count <30 ×109/L.
  • Corrected reticulocyte count <2% (using the following calculation; (% reticulocyte x % hematocrit) / normal hematocrit [45%]).
  • Positive for human immunodeficiency virus (HIV) or hepatitis C antibody.
  • Positive for hepatitis B surface antigen.
  • Splenectomy within 3 months of screening.
  • Any T-cell or NK-cell NHL, and any moderate- or high-grade B-cell lymphoma, including Burkitt lymphoma, lymphoblastic B-cell lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, or small non-cleaved cell non-Burkitt lymphoma.
  • Received any cytotoxic (other than azathioprine, chlorambucil, low-dose methotrexate, or low-dose oral cyclophosphamide [≤100 mg/day]), or any non-anti-CD20 mAb therapy in the 3 months prior to screening.
  • Any exposure to an investigational drug or device within 30 days prior to screening.
  • IVIG treatment within 30 days of screening.
  • Plasmapheresis or immunoadsorption within 30 days of screening.
  • Cellular therapy, including chimeric antigen receptor and T-cell (CAR-T), at any time prior to screening.
  • Use of any immunosuppressive drugs within 3 months of screening, not including those allowed by the inclusion criteria.
  • Active infection or history of recurrent infections.
  • Serum total IgG <600 mg/dL.
  • Subject has any current medical condition that, in the opinion of the Investigator, may compromise their safety or compliance, preclude successful conduct of the study, or interfere with interpretation of the results (eg, a significant pre-existing illness or other major comorbidity that the Investigator considers may confound the interpretation of the study results).
  • Any vaccination within 2 weeks of screening.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status

Rochester, Minn.

Mayo Clinic principal investigator

Ronald Go, M.D.

Closed for enrollment

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20337813

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