IRB Study Number 23-549
Status Recruiting
Institute Taussig Cancer Institute
Description
2.1.1. Primary Objectives
• Assess the safety and tolerability profile of escalating dose levels of ABC008 in
subjects with T-LGLL
2.1.2. Secondary Objectives
• Assess the efficacy of ABC008;
• Assess the PD profile of ABC008;
• Assess the PK profile of ABC008.
2.1.3. Exploratory Objectives
• Assess the immunogenicity of ABC008;
• Assess changes in health-related quality of life (HRQoL) related to ABC008;
• Explore gene expression, genetic, and biomarker analyses associated with the disease and response to ABC008;
• Explore PK, PD, and immunogenicity correlations associated with safety and response to ABC008;
• Explore cytokine levels in relation to response to ABC008.
Inclusion Criteria
- Has the ability to personally provide written, signed, and dated informed consent or eConsent to participate in the study;
- Has an understanding, ability, and willingness to fully comply with study procedures and restrictions;
- Is at least 18 years of age;
- Has body mass index (BMI) ≤35 kg/m2;
- Has a documented diagnosis of T-LGLL;
- Subject has any 1 or more of the following at Screening:
a. ANC <0.5 x 109/L;
b. 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);
c. Hgb <8 g/dL or packed red blood cell (PRBC) transfusion frequency ≥1 time in the 4 weeks immediately prior to Screening;
d. 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 an anticipated life expectancy of at least 12 months prior to study drug administration, per Investigator or Sponsor opinion;
- Has adequate hepatic or renal function at Screening, as indicated by:
a. Serum ALT or AST <2.5x the ULN;
b. Total bilirubin ≤1.5 ULN;
c. Estimated GFR ≥45 mL/min/1.73m2 by CKD-EPI equation corrected for the subject’s actual body surface area calculated by the Mosteller equation and divided by 1.73;
- Willingness to avoid pregnancy or fathering children based on the criteria below:
a. Male subjects must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from Screening through 12 weeks after the last dose of study treatment or during the study, whichever period is longer, and refrain from donating sperm during this period. Permitted methods in preventing pregnancy (as below) should be communicated to the subject and his understanding confirmed;
b. Women of childbearing potential must not be pregnant and must have a negative serum pregnancy test at Screening and a negative urine pregnancy test before the first dose on Day 1 and must agree to take appropriate precautions to avoid pregnancy from Screening through 12 weeks after the last dose of study treatment or during the study, whichever period is longer, and refrain from donating oocytes during this period. Permitted methods in preventing pregnancy (as outlined in Section 5.3.5) should be communicated to the subject and her understanding confirmed;
- Agree 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 EOS/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 × 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 or is unable to forgo use of any of the following therapies in the time frames specified prior to Day 1 (unless otherwise specified):
a. Polychemotherapy, e.g., CHOP) or CHOP-like regimens (e.g., cyclophosphamide [CTX], doxorubicin or hydroxyrubicin, vincristine, and prednisone); cytosine arabinoside-containing regimens; fludarabine with mitoxantrone – any use ever;
b. Antithymocyte globulin (ATG) or T-cell-depleting biologic therapies, e.g., alemtuzumab, siplizumab or biosimilar versions of these agents –12 months;
c. B cell-depleting biologic therapies, e.g., inebilizumab, ofatumumab, ocrelizumab, rituximab or biosimilar versions of these agents – 12 months;
d. Average systemic prednisone or prednisone equivalent (e.g., oral, IV, intramuscular [IM]) ≥20 mg/day or change in dose of systemic prednisone or prednisone equivalent (inhaled, nasal, ophthalmic, otic, topical administration of corticosteroids permitted) – 4 weeks;
e. CTX, CSA, MTX, Janus kinase (JAK) inhibitors, tacrolimus, sirolimus – 4 weeks;
f. IV, SC, or IM gamma globulin therapy – 12 weeks;
g. Concomitant growth factors (e.g., granulocyte colony stimulating factor [G-CSF], erythropoietin) if the dose has not been stable for at least 8 weeks prior to Day 1, is not expected to stay stable for the duration of the study, or has been discontinued – 4 weeks;
h. Purine analogs (e.g., fludarabine, cladribine, deoxycoformycin [pentostatin], bendamustine) – 4 weeks, unless administered for >3 courses, then any use ever;
i. Any other chemotherapeutic agent not already indicated above (e.g., alkylating agents [other than bendamustine or CTX as already delineated above]; nitrosoureas; antimetabolites [other than cladribine, fludarabine, deoxycoformycin or MTX as already delineated above]; anti-tumor antibiotics [e.g., anthracyclines, bleomycin]; topoisomerase inhibitors; mitotic inhibitors; tyrosine kinase inhibitors) – any use ever;
j. Any non-cell-depleting biologic therapy, e.g., interleukin (IL)-6 inhibitors, IL-15 inhibitors, PD-1/PD-L1 inhibitors, TNFα inhibitors, denosumab, abatacept – 12 weeks;
k. Note: Etanercept only required to be washed out for 4 weeks;
l. Any other immunosuppressant therapy not already specified above – 12 weeks;
m. Note: Hydroxychloroquine in subjects with RA is allowed at up to 400 mg/day if the dose has been stable for at least 12 weeks prior to Day 1;
n. Any ayurvedic, herbal, or traditional Chinese medications/supplements – Screening Visit onward;
o. Any investigational compound if not already specified above – 4 weeks or 5 half-lives, whichever is longer;
- Has any other autoimmune or autoinflammatory disease other than RA, IBM, secondary Sjogren’s syndrome (SS), or thyroid disease, unless there is agreement between the study medical team and the PI that the subject’s autoimmune or autoinflammatory disease and/or concomitant treatment(s) do not present risk to the subject that would outweigh potential benefit(s) to participation in this study;
a. If the subject has RA, the subject is not expected to change therapy for the underlying RA for the duration of the study from the Day 1 visit if undergoing washout of therapies to comply with Exclusion Criterion 5 or from the Screening Visit if no washouts required to comply with Exclusion Criterion 5;
− The subject does not need to undergo washout during the screening window if the Investigator determines there is a risk for clinically-significant RA exacerbation.
b. If the subject has thyroid disease, free T4 and thyroid stimulating hormone (TSH) levels must be within normal limits or the subject should be on replacement therapy;
Has another myelo-/lympho-proliferative disorder or malignancy (other than 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;
Is a female with a known history in the 3 years prior to Screening of an abnormal Pap smear attributed to human papilloma virus (HPV);
Has a history or current diagnosis of active tuberculosis (TB), recent contact (within 12 weeks of Screening) with an individual(s) with active TB, or positive QuantiFERON®-TB Gold or Gold Plus test (QFT) at Screening or within 12 weeks of Screening. Subjects with an initial indeterminate QFT result must have a negative result on repeat testing to participate. In the event of a positive QFT result, subjects can be screened via chest x-ray to rule out active TB disease. Subjects with documented evidence of treatment per the Centers for Disease Control guidelines of latent TB infection will be permitted to enter the study if they have no known history of subsequent contact with an individual with active TB;
Has a history of herpes zoster infection that was disseminated, required hospitalization, or required IV antiviral therapy in the 24 weeks prior to Day 1;
EBV or CMV plasma viral load that is greater than the lower limit of quantification at Screening and confirmed on repeat testing prior to dosing;
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 or treatment with IV antimicrobials within 4 weeks prior to Day 1 or oral antimicrobials within 14 days prior to Day 1. Onychomycosis, vaginal mycosis, or herpes infections under control from stable ongoing treatment/prophylactic therapy are permitted;
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., corneal, solid, bone marrow) or is expected to receive one during the study;
Has had any of the following medical conditions in the 24 weeks prior to Day 1 unless otherwise specified:
a. New York Heart Association Class III or IV congestive heart failure or known left ventricular ejection fraction of ≤40%;
b. Unstable angina pectoris, myocardial infarction, or coronary angioplasty/stent;
c. Long QT syndrome;
d. Per the central ECG obtained at Screening or the local ECG obtained at Day 1, QT interval corrected by Fridericia’s formula (QTcF) >480 msec;
e. Uncontrolled clinically significant or symptomatic conduction abnormalities/arrythmias (asymptomatic premature atrial/ventricular contractions, 1st degree atrioventricular block, or left/right bundle branch block permitted);
f. Uncontrolled hypertension (subjects with systolic blood pressure <160 AND diastolic blood pressure <100 at Screening and BL and on treatment for hypertension are permitted);
g. Cerebrovascular accident, transient ischemic attack;
h. Pulmonary embolism;
i. Uncontrolled or severe (e.g., CTCAE v5.0 ≥Grade 3) hepatic diseases, e.g., alcohol related liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis;
j. Uncontrolled or severe (e.g., CTCAE v5.0 ≥Grade 3) renal diseases, e.g., diabetic or hypertensive renal disease, glomerulonephritis, polycystic kidney disease;
k. Neurologic condition, e.g., neurodegenerative disease;
l. Psychiatric illness, e.g., suicidal ideation, psychiatric hospitalization;
m. Uncontrolled or severe pulmonary disease (e.g., CTCAE v5.0 ≥Grade 3) e.g., respiratory insufficiency requiring oxygenation or pulmonary fibrosis, asthma, or chronic obstructive pulmonary disease;
n. Uncontrolled or severe (e.g., CTCAE v5.0 ≥Grade 3) metabolic disease, e.g., diabetes mellitus or thyroid disorders;
o. Suspected or known drug or alcohol abuse in the 24 weeks prior to Screening; medicinal marijuana is permitted;
Is a female who is lactating or within 4 weeks of completion of lactation prior to Day 1;
Is currently participating in another interventional clinical trial at Screening or Day 1 or intends to do so during this 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.
