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

• ClinicalTrials.gov Identifier: NCT05532722
• Recruitment Status: Recruiting
• First Posted: September 8, 2022
• Last Update Posted: May 1, 2023
• Sponsor: Abcuro, Inc.
• Information provided by (Responsible Party): Abcuro, Inc.

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
T-cell Large Granular Lymphocytic Leukemia	Drug: ABC008	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 15 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Study of ABC008 in Subjects With T-cell Large Granular Lymphocytic Leukemia (T-LGLL)
• Actual Study Start Date: September 28, 2022
• Estimated Primary Completion Date: December 2023
• Estimated Study Completion Date: December 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: ABC008 Dose Level 1 Cohort; 0.25 mg / kg ABC008 Subjects receive ABC008 every 8 weeks. Cohorts receive escalating doses of ABC008 until completion of cohort 4 or any cohort is determined to have exceeded the maximum tolerated dose.	Drug: ABC008; Given subcutaneous injection
Experimental: ABC008 Dose Level 2 Cohort; 0.75 mg / kg ABC008 Subjects receive ABC008 every 8 weeks. Cohorts receive escalating doses of ABC008 until completion of cohort 4 or any cohort is determined to have exceeded the maximum tolerated dose.	Drug: ABC008; Given subcutaneous injection
Experimental: ABC008 Dose Level 3 Cohort; 1.5 mg / kg ABC008 Subjects receive ABC008 every 8 weeks. Cohorts receive escalating doses of ABC008 until completion of cohort 4 or any cohort is determined to have exceeded the maximum tolerated dose.	Drug: ABC008; Given subcutaneous injection
Experimental: ABC008 Dose Level 4 Cohort; 3.0 mg / kg ABC008 Subjects receive ABC008 every 8 weeks. Cohorts receive escalating doses of ABC008 until completion of cohort 4 or any cohort is determined to have exceeded the maximum tolerated dose.	Drug: ABC008; Given subcutaneous injection

Outcome Measures

Primary Outcome Measures :

1. Incidence, nature, and severity of treatment-emergent AEs and SAEs as determined by NCI CTCAE v5.0 [ Time Frame: Through Study Completion an average of 48 weeks ]

Secondary Outcome Measures :

1. Change from baseline in safety lab (Hematology) [ Time Frame: Through Study Completion an average of 48 weeks ]
2. Change from baseline in safety lab (Chemistry) [ Time Frame: Through Study Completion an average of 48 weeks ]
3. Change from baseline in safety lab (Coagulation) [ Time Frame: Through Study Completion an average of 48 weeks ]
   Includes the following coagulation labs: INR and aPTT
4. Change from baseline in safety lab (Complement) [ Time Frame: Through Study Completion an average of 48 weeks ]
   Includes the following complement labs: C3 and CH50
5. Change from baseline in safety lab (Cytokines) [ Time Frame: Through Study Completion an average of 48 weeks ]
6. Change from baseline in safety lab (CMV Viral Load) [ Time Frame: Through Study Completion an average of 48 weeks ]
7. Change from baseline in safety lab (EBV Viral Load) [ Time Frame: Through Study Completion an average of 48 weeks ]
8. Change from baseline in ECG (Rhythm) [ Time Frame: Through Study Completion an average of 48 weeks ]
9. Change from baseline in ECG (Heart Rate) [ Time Frame: Through Study Completion an average of 48 weeks ]
10. Change from baseline in ECG parameters [ Time Frame: Through Study Completion an average of 48 weeks ]
    Includes the following ECG parameters: RR interval, PR interval, QRS interval, QT interval, QT interval corrected by Bazett's formula, and QTcF
11. Change from baseline in vital sign (Systolic and diastolic blood pressure) [ Time Frame: Through Study Completion an average of 48 weeks ]
12. Change from baseline in vital sign (temperature) [ Time Frame: Through Study Completion an average of 48 weeks ]
13. Change from baseline in vital sign (respiratory rate) [ Time Frame: Through Study Completion an average of 48 weeks ]
14. Change from baseline in vital sign (pulse rate) [ Time Frame: Through Study Completion an average of 48 weeks ]
15. Percentage of subjects demonstrating overall response (defined as total number of subjects with CR or PR) at all time points assessed [ Time Frame: Day 1 and throughout the 48 weeks of follow up ]
16. Percentage of subjects demonstrating complete response at all time points assessed [ Time Frame: Day 1 and throughout the 48 weeks of follow up ]
    A complete response is defined by normalization of hemoglobin, neutrophil and platelet levels without transfusion
17. Percentage of subjects demonstrating partial response at all time points assessed [ Time Frame: Day 1 and throughout the 48 weeks of follow up ]
    A partial response is defined by improvement in any of the following criteria but not all: hemoglobin, neutrophil and platelet levels without transfusion
18. Duration of response at all time points assessed [ Time Frame: Day 1 and throughout the 48 weeks of follow up ]
19. Overall survival at Week 48 [ Time Frame: Day 1 and throughout the 48 weeks of follow up ]
20. The change from baseline in levels of KLRG1 expressing lymphocytes over time [ Time Frame: Day 1 and throughout the 48 weeks of follow up ]
21. The change from baseline in levels of T-LGL counts over time [ Time Frame: Day 1 and throughout the 48 weeks of follow up ]
22. The change from baseline in levels of lymphocyte subsets over time [ Time Frame: Day 1 and throughout the 48 weeks of follow up ]
23. The maximum serum concentration [CMax] of ABC008 [ Time Frame: Day 1 and throughout the 48 weeks of follow up ]
24. The time to maximum concentration [TMax] of ABC008 [ Time Frame: Day 1 and throughout the 48 weeks of follow up ]
25. The area under the concentration-time curve [AUC] of ABC008 [ Time Frame: Day 1 and throughout the 48 weeks of follow up ]
26. The apparent clearance [CL/F] of ABC008 [ Time Frame: Day 1 and throughout the 48 weeks of follow up ]
27. The apparent volume of distribution [Vd/F] of ABC008 [ Time Frame: Day 1 and throughout the 48 weeks of follow up ]
28. The elimination half-life [t½] of ABC008 [ Time Frame: Day 1 and throughout the 48 weeks of follow up ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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)
  • 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
  • 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 received more than 3 immunosuppressant therapies/chemotherapeutic agents (except for prednisone/prednisone equivalent) for the treatment of T LGLL.
• 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.

Contacts and Locations

Contacts

Contact: Michael McClain; 617-865-5078; LGL-101_ClinicalTrial@abcuro.com

Locations

United States, California

City of Hope; Recruiting

Duarte, California, United States, 91010

Contact: Ryotaro Nakamura, M.D. 877-467-3411

Principal Investigator: Ryotaro Nakamura, M.D.

University of Southern California; Recruiting

Los Angeles, California, United States, 90033

Contact: Christine Duran duran_c@med.usc.edu

Principal Investigator: Howard Liebman, M.D.

United States, Massachusetts

Massachusetts General Hospital; Recruiting

Boston, Massachusetts, United States, 02114

Contact: Salvia Jain 617-724-4000

Principal Investigator: Salvia Jain, M.D.

Dana-Farber Cancer Institute; Recruiting

Boston, Massachusetts, United States, 02215

Contact: DFCI Clinical Trial Hotline 877-338-7425

Principal Investigator: Eric Jacobsen, M.D.

United States, New York

SUNY Upstate Medical University; Recruiting

Syracuse, New York, United States, 13210

Contact: Patricia Benz 315-464-8253 benzp@upstate.edu

Principal Investigator: Bernard Poiesz, M.D.

United States, Utah

Huntsman Cancer Institute, University of Utah; Recruiting

Salt Lake City, Utah, United States, 84112

Contact: David L Samuel 801-587-9834 David.Samuel@hci.utah.edu

Principal Investigator: Paul J Shami, M.D.

Sponsors and Collaborators

Abcuro, Inc.

More Information

• Responsible Party: Abcuro, Inc.
• ClinicalTrials.gov Identifier: NCT05532722
• Other Study ID Numbers: ABC008-LGL-101
• First Posted: September 8, 2022
• Last Update Posted: May 1, 2023
• Last Verified: April 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Abcuro, Inc.:

T-cell Large Granular Lymphocytic Leukemia; T-LGLL

Additional relevant MeSH terms:

Leukemia; Leukemia, Lymphoid; Leukemia, Large Granular Lymphocytic; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, T-Cell