ABC008 in Subjects with T-cell Large Granular Lymphocytic Leukemia (T-LGLL)

Abcuro

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: T-cell Large Granular Lymphocytic Leukemia

Treatments: Drug: ABC008

Study type: Interventional

Funder types: Industry

Identifiers

NCT05532722

ABC008-LGL-101

Details and patient eligibility

About

An open label, ascending dose study for adult subjects with T-cell Large Granular Lymphocytic Leukemia (T-LGLL)

Enrollment: 21 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Is at least 18 years of age.

• Has body mass index (BMI) ≤35 kg/m2.

• Has a documented diagnosis of T LGLL.

• Has any 1 or more of the following at Screening:

  • Absolute neutrophil count (ANC) <0.5 x 109/L
  • ANC ≥0.5 x 109/L and <1.0 x 109/L associated with recurrent infection (≥2 or more infections requiring antimicrobial therapy within the previous 12 months)
  • Hemoglobin (Hgb) <8 g/dL or packed red blood cell transfusion frequency ≥1 time in the 4 weeks immediately prior to Screening
  • Hgb ≥8 g/dL and <10 g/dL accompanied by documented symptoms of anemia, e.g., fatigue, weakness, pale or yellowish skin, irregular heartbeat, shortness of breath, dizziness, or lightheadedness.

• Has adequate hepatic and renal function at Screening, as indicated by:

  • Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST); <2.5x the upper limit of normal (ULN)
  • Total bilirubin ≤1.5 ULN; subjects with Gilbert syndrome must have a total bilirubin <3.0x ULN with direct bilirubin <1.0x ULN at time of Screening
  • Estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) equation corrected for the body surface area of the subject calculated by the Mosteller equation and divided by 1.73

• Agrees to adhere to the current Centers for Disease Control advice regarding minimizing exposure to severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) from the first Screening Visit until the End of Study (EOS)/Early Termination Visit (ETV).

Exclusion criteria

• Has reactive large granular lymphocytosis.
• Has active anemia secondary to confirmed etiologies other than T-LGLL, including known vitamin or mineral deficiency, gastrointestinal bleeding, or genetic disorder; or has active neutropenia secondary to known vitamin or mineral deficiencies or genetic disorder.
• Has a platelet count ≤20 x 109/L or other clinically significantly abnormal laboratory results not related to the underlying condition in the Investigator's or Sponsor's opinion at Screening.
• Has known hypersensitivity to any component of the formulation of ABC008, or history of anaphylaxis to any prior mAb therapy.
• Has any other autoimmune or autoinflammatory disease other than RA, inclusion body myositis (IBM), secondary Sjogren's syndrome (SS), or thyroid disease.
• Has another myelo /lympho proliferative disorder or malignancy (other than monoclonal gammopathy of unknown significance [MGUS] not requiring treatment) within the past 5 years prior to Screening except completely resected nonmelanoma skin cancer, curatively treated localized prostate cancer, and completely resected carcinoma in situ at any site.
• Has a current diagnosis of active tuberculosis (TB)
• Has a history of herpes zoster infection that was disseminated, required hospitalization, or IV antiviral therapy in the 24 weeks prior to Day 1.
• Active, chronic, or past history of hepatitis B virus or hepatitis C virus (HCV) infection (hepatitis B core antibody or surface antigen positive, or HCV antibody positive with reflex HCV ribonucleic acid [RNA] positive at Screening; individuals who have received curative therapy for HCV are permitted if therapy was completed at least 24 weeks prior to Screening and subject is HCV RNA negative);
• Has known active bacterial, viral, fungal, or atypical mycobacterial infection, or any major episode of infection that required hospitalization
• Has received live (including attenuated) vaccination in the 30 days prior to Day 1 or killed vaccine within 14 days prior to Day 1.
• Is human immunodeficiency virus (HIV) positive by antigen/antibody test, human T cell lymphotropic virus (HTLV 1 or 2) positive by antibody test.
• Has had major surgery (defined as surgery requiring general or regional anesthesia) within 6 weeks prior to Day 1 or is expected to receive surgery during the study.
• Has a history of organ transplant (e.g., solid, bone marrow) or is expected to receive one during the study.
• Has any other condition or social situations that would interfere with the subject's study participation, increase the risk associated with study participation or investigational product administration, interfere with the interpretation of study results, or would otherwise make the subject inappropriate for entry into this study in the Investigator's or Sponsor's opinion.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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21 participants in 5 patient groups

ABC008 Dose Level 1 Cohort

Experimental group

Description:

0.25 mg / kg ABC008 Subjects receive ABC008 every 8 weeks. Cohorts receive escalating doses of ABC008 until completion of cohort 5 or any cohort is determined to have exceeded the maximum tolerated dose.

Treatment:

Drug: ABC008

ABC008 Dose Level 2 Cohort

Experimental group

Description:

0.75 mg / kg ABC008 Subjects receive ABC008 every 8 weeks. Cohorts receive escalating doses of ABC008 until completion of cohort 5 or any cohort is determined to have exceeded the maximum tolerated dose.

Treatment:

Drug: ABC008

ABC008 Dose Level 3 Cohort

Experimental group

Description:

1.5 mg / kg ABC008 Subjects receive ABC008 every 8 weeks. Cohorts receive escalating doses of ABC008 until completion of cohort 5 or any cohort is determined to have exceeded the maximum tolerated dose.

Treatment:

Drug: ABC008

ABC008 Dose Level 4 Cohort

Experimental group

Description:

3.0 mg / kg ABC008 Subjects receive ABC008 every 8 weeks OR 1.5 mg / kg Subjects receive ABC008 every 4 weeks. Cohorts receive escalating doses of ABC008 until completion of cohort 5 or any cohort is determined to have exceeded the maximum tolerated dose.

Treatment:

Drug: ABC008

ABC008 Dose Level 5 Cohort

Experimental group

Description:

3.0 mg / kg ABC008 Subjects receive ABC008 every 4 weeks. Cohorts receive escalating doses of ABC008 until completion of cohort 5 or any cohort is determined to have exceeded the maximum tolerated dose.

Treatment:

Drug: ABC008