A Phase 3 Study of the Safety of Trogarzo® Administered as an Undiluted "IV Push" Over a Reduced Interval or as an Intramuscular Injection in Clinically Stable HIV-1 Infected Trogarzo® Experienced Patients and Healthy HIV-uninfected Volunteers

TMB-302

This study is designed to assess the safety and pharmacokinetic profile of 800 mg Trogarzo once every two weeks administered via "IV Push" or intramuscular injection. An initial "Sentinel Group" of 5 participants will begin receiving 800mg Trogarzo on a gradual schedule of increasing concentration and decreasing administration time until undiluted IV Push over 30 seconds is achieved, while safety and pharmacokinetics are evaluated. If no safety signals are seen, the Core Group of 15 participants will be enrolled. The Core Group will receive 800mg Trogarzo via undiluted IV Push over 30 seconds while safety and pharmacokinetics are monitored. After completion of the IV Push portion of the study, a second group of 20 participants will be enrolled to evaluate the safety and pharmacokinetics of administration of 800mg via intramuscular injection.

2019-05-30

2022-10-17

2022-10-31

Completed

Early phase I

46

Inclusion Criteria - HIV-infected participants (all groups): 1. Are capable of understanding and have voluntarily signed the informed consent document 2. Currently receiving a stable Trogarzo-containing ARV regimen for a minimum of 3 months, and no change in background ARVs anticipated over the period of study participation; a stable regimen is defined as having no changes in dose or frequency and no interruptions greater than or equal to 2 weeks during the 3 month period 3. Have no acquired immunodeficiency syndrome (AIDS)-defining events in the 3 months before Screening, other than cutaneous Kaposi's sarcoma or wasting syndrome due to HIV 4. Are able and willing to comply with all protocol requirements and procedures 5. Are 18 years of age or older 6. Have a life expectancy that is \>6 months. 7. Have a viral load \<1,000 copies/mL at Screening 8. CD4+ T-cell count \> 50 cells/mm3 at Screening 9. Prothrombin time (PT) and partial thromboplastin time (PTT) \<1.5 times the upper limit of normal (IM Group only) Inclusion Criteria - Healthy Volunteers (all groups): 1. Healthy volunteers born male and female as assessed by medical history and physical examination 2. Aged \>18 and \<50 years at the time of Screening 3. Ability and willingness to provide written informed consent 4. Willingness to comply with protocol schedule 5. Willingness to undergo HIV-1 testing 6. Non-reactive 4th generation point of care HIV-1 test at Screening 7. Hepatitis B Surface antigen negative 8. Hepatitis C antibody negative, or if reactive, Hepatitis C RNA undetectable in plasma 9. PT and PTT \<1.5 times the upper limit of normal (IM Group only) 10. Volunteers born female of reproductive potential who are sexually active with a male sex partner must agree to use one effective method of contraception from the time of signing the consent to completion of the study and agree to pregnancy testing as per the schedule of events. Volunteers born female with reproductive potential are defined as pre-menopausal volunteers born female who have not had a sterilization procedure (e.g., hysterectomy, bilateral oophorectomy, tubal ligation or salpingectomy). Volunteers born female are considered menopausal if they have not had a menses for at least 12 months and have a follicle-stimulating hormone (FSH) of greater than 40 IU/L or if FSH testing is not available, they have had amenorrhea for 24 consecutive months. Exclusion Criteria - HIV-infected participants (all groups): 1. Any active AIDS-defining illness according to the Centers for Disease Control and Prevention (CDC) Revised Surveillance Case Definitions for HIV Infection 2008 (Morbidity and Mortality Weekly Report (MMWR) Vol.57/No. RR-10, Appendix A), or history of the same during the 3 months preceding Screening, with the following exceptions: cutaneous Kaposi's sarcoma and wasting syndrome due to HIV 2. Any significant diseases (other than HIV-1 infection) or clinically significant findings, including psychiatric and behavioral problems, determined from Screening, medical history, and/or physical examination that, in the investigator's opinion, would preclude the subject from participating in this study 3. Any significant acute illness within 1 week before the initial administration of study drug 4. Any active infection secondary to HIV requiring acute therapy; however, subjects that require maintenance therapy (i.e., secondary prophylaxis for opportunistic infections) will be eligible for the study 5. Any immunomodulating therapy (including interferon), systemic steroids, or systemic chemotherapy within 12 weeks before Enrollment 6. Any vaccination within 7 days before Day 1 7. Any female subject who either is pregnant, intends to become pregnant, or is currently breastfeeding 8. Any current alcohol or illicit drug use that, in the investigator's opinion, will interfere with the subject's ability to comply with the study schedule and protocol evaluations 9. Any radiation therapy during the 28 days before first administration of study medication 10. Any Grade 3 or 4 laboratory abnormality according to the Division of AIDS (DAIDS) grading scale, except for the following asymptomatic Grade 3 events: * triglyceride elevation * total cholesterol elevation * or Grade 3 or 4 reductions in levels of CD4+ T cells 11. History of coagulopathy that would preclude administration of IM injections (IM Group only) 12. Skin rashes or tattoos that would prevent ability to assess IM injection for injection-site reactions (IM Group only) 13. Use of high-dose aspirin, clopidogrel, prasugrel, ticagrelor, dipyridamole or other antiplatelet medication that would interfere with the ability to receive IM injections (IM Group only). Exclusion Criteria - Healthy Volunteers (all groups): 1. Confirmed HIV-1 infection 2. At high risk of severe COVID-19 disease as defined by one of the following: * History of hypertension, atherosclerotic cardiovascular disease (ASCVD), coronary artery disease, diabetes mellitus * History of asthma or chronic pulmonary disease * History of renal disease and chronic renal insufficiency * BMI over 35 3. Any acute or chronic medical condition that in the opinion of the investigator would preclude participation 4. Chronic autoimmune disease 5. Active IV drug use 6. Excessive use of alcohol or recreational drugs that in the opinion of the investigator would preclude participation 7. Decompensated psychiatric illness 8. Need for chronic immunotherapy including systemic corticosteroids, other MAb therapy, or immunosuppressive drugs 9. Volunteers born female who are pregnant, lactating, or planning on becoming pregnant over the study period 10. Any of the following laboratory parameters: * Hemoglobin \<10.0 g/dL * Absolute neutrophil count \<1,000/mm3 * Absolute lymphocyte count \<500/mm3 * Platelet count \<100,000/mm3 * Creatinine \>1.25x upper limit of normal (ULN) * Aspartate aminotransferase (AST) \>1.5x ULN * Alanine aminotransferase (ALT) \>1.5x ULN * Glucose (non-fasting) \>160 mg/dL * Proteinuria: 2+ or greater * Hematuria: \>10 red blood cells (RBCs) per high-power field 11. Previous receipt of an experimental MAb for HIV-1treatment or prevention in a research study 12. History of severe allergic reactions to drugs, vaccines, or drug infusion 13. Participation in another investigational clinical trial within the past 12 weeks or anticipated during the course of the current study 14. History of coagulopathy that would preclude administration of IM injections (IM Group only) 15. Skin rashes or tattoos that would prevent ability to assess IM injection for injection-site reactions (IM Group only) 16. Use of high-dose aspirin, clopidogrel, prasugrel, ticagrelor, dipyridamoleor any other antiplatelet medication that would interfere with the ability to receive IM injections (IM Group only).

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'SEQUENTIAL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 46, 'type': 'ACTUAL'}}

2023-09-21