Study of the Safety of Trogarzo™ Administered as an Undiluted "IV Push" or an Intramuscular Injection

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

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.

Study Overview

• Status: Completed
• Conditions: HIV-1-infection
• Intervention / Treatment: Drug: ibalizumab-uiyk

Detailed Description

This goal of this Phase 3 is to evaluate the safety and pharmacokinetics of administering Trogarzo 800 mg once every two weeks as an undiluted IV Push over 30 seconds, and as an intramuscular injection in clinically stable HIV-1 infected patients currently receiving treatment with a stable Trogarzo-containing regimen and in healthy volunteers.

The first five (5) patients enrolled will comprise the Sentinel Group. Patients six (6) through twenty (20) (the Core Group) will not be screened until the Sentinel Group has completed Day 99 (14 weeks) of the study and the DSMB has reviewed the data accumulated and given approval for enrollment of the Core Group to proceed.

The Sentinel Group will receive 2 successive doses of Trogarzo in accordance with the prescribing information. Safety and pharmacokinetic data from these administrations will serve as the comparator for each study participant. Beginning at Day 29 and continuing through Day 85, Sentinel Group participants will begin receiving the prescribed dosage of Trogarzo once every two weeks through Day 85 of the study on a schedule of increasing drug concentration and decreasing administration time at each visit to achieve an undiluted IV Push administration of Trogarzo over 30 seconds.

After review of data from the Sentinel Group by a DSMB, if approved the study will continue with enrollment of the Core Group, which will enroll both clinically stable HIV-infected patients on a stable Trogarzo-containing treatment regimen and healthy volunteers. The HIV-infected participants in the Core Group will receive 2 successive doses of Trogarzo in accordance with the prescribing information. Safety and pharmacokinetic data from these administrations will serve as the comparator for each study participant. Thereafter, HIV-infected participants in the Core Group will receive the prescribed dosage of Trogarzo via undiluted IV Push over 30 seconds through Day 71 of the study.

Healthy Volunteers in the Core Group will receive a single loading dose of 2000mg of Trogarzo, followed by three successive doses of 800mg Trogarzo in accordance with the prescribing information in order to reach steady state before pharmacokinetic data for analysis are collected. Thereafter, Healthy Volunteers in the Core Group will follow the same schedule of drug administration and assessments as the HIV-infected participants in the Core Group.

HIV-infected participants in the Intramuscular Injection Group will receive 2 successive doses of Trogarzo in accordance with the prescribing information. Safety and pharmacokinetic data from these administrations will serve as the comparator for each study participant. Thereafter, HIV-infected Intramuscular Injection Group participants will receive the prescribed dosage of Trogarzo via intramuscular injection beginning at Day 29 and continuing through Day 71.

Healthy Volunteers in the Intramuscular Injection Group will receive a single loading dose of 2000mg of Trogarzo, followed by three successive doses of 800mg Trogarzo in accordance with the prescribing information in order to reach steady state before pharmacokinetic data for analysis are collected. Thereafter, Healthy Volunteers in the Intramuscular Injection Group will follow the same schedule of drug administration and assessments as the HIV-infected participants in the Intramuscular Injection Group.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90069
      • Anthony Mills MD Inc.
  • Florida
    • Fort Lauderdale, Florida, United States, 33316
      • Gary Richmond MD, PA
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center
  • Texas
    • Dallas, Texas, United States, 75246
      • North Texas Infectious Disease Consultants

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sentinel Group; Five (5) participants will receive two successive doses of 800mg ibalizumab administered in accordance with the prescribing information followed by five (5) successive 800mg doses on a schedule gradually increasing drug concentration and decreasing administration time.	Drug: ibalizumab-uiyk; Ibalizumab-uiyk is an IgG4 monoclonal antibody targeting domain 2 of the extracellular portion of the CD4 protein. Ibalizumab-uiyk is FDA approved for the treatment of multi-drug resistant HIV in treatment experienced patients.; Other Names: Trogarzo
Experimental: Core Group; HIV-infected Core Group participants will receive two successive doses of 800mg ibalizumab (Trogarzo) administered in accordance with the prescribing information followed by four (4) successive 800mg doses via undiluted IV Push over 30 seconds. Healthy Volunteer Core Group participants will receive a single 2000mg loading dose followed by three successive doses of 800mg in accordance with the prescribing information in order to reach steady state. Thereafter, Healthy Volunteers will receive two successive doses of 800mg ibalizumab (Trogarzo) administered in accordance with the prescribing information followed by four (4) successive 800mg doses via undiluted IV Push over 30 seconds.	Drug: ibalizumab-uiyk; Ibalizumab-uiyk is an IgG4 monoclonal antibody targeting domain 2 of the extracellular portion of the CD4 protein. Ibalizumab-uiyk is FDA approved for the treatment of multi-drug resistant HIV in treatment experienced patients.; Other Names: Trogarzo
Experimental: Intramuscular Injection Group; HIV-infected Intramuscular Injection Group participants will receive two successive doses of 800mg ibalizumab (Trogarzo) administered in accordance with the prescribing information followed by four (4) successive 800mg doses via Intramuscular Injection. Healthy Volunteer Intramuscular Injection Group participants will receive a single 2000mg loading dose followed by three successive doses of 800mg in accordance with the prescribing information in order to reach steady state. Thereafter, Healthy Volunteers will receive two successive doses of 800mg ibalizumab (Trogarzo) administered in accordance with the prescribing information followed by four (4) successive 800mg doses via intramuscular injection.	Drug: ibalizumab-uiyk; Ibalizumab-uiyk is an IgG4 monoclonal antibody targeting domain 2 of the extracellular portion of the CD4 protein. Ibalizumab-uiyk is FDA approved for the treatment of multi-drug resistant HIV in treatment experienced patients.; Other Names: Trogarzo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of Trogarzo given as IV Push over 30 seconds in Sentinel Group	Percent of subjects in Sentinel Group who complete 100% of all Trogarzo administrations given as infusion/bolus/push as per protocol	12 weeks
Safety of Trogarzo given as IV Push over 30 seconds in Core Group	Percent of subjects in Core Group who complete 100% of all Trogarzo administrations given as infusion/bolus/push as per protocol	10 weeks
Pharmacokinetics(1) of Trogarzo infusion versus IV Push in Sentinel Group	Ratio of Area Under the Curve of Serum levels of Trogarzo given by 15 minute infusion versus Area Under the Curve of Serum levels of Trogarzo given by IV Push over 30 seconds	Day 1 infusion versus Day 85 IV Push
Pharmacokinetics(2) of Trogarzo infusion versus IV Push in Sentinel Group	Ratio of Trough Serum levels of Trogarzo given by 15 minute infusion versus Trough Serum levels of Trogarzo given by IV Push over 30 seconds	Day 1 infusion versus Day 85 IV Push
Pharmacokinetics(1) of Trogarzo infusion versus IV Push in Core Group	Ratio of Area Under the Curve of Serum levels of Trogarzo given by 15 minute infusion versus Area Under the Curve of Serum levels of Trogarzo given by IV Push over 30 seconds	Day 1 infusion versus Day 71 IV Push
Pharmacokinetics(2) of Trogarzo infusion versus IV Push in Core Group	Ratio of Trough Serum levels of Trogarzo given by 15 minute infusion versus Trough Serum levels of Trogarzo given by IV Push over 30 seconds	Day 1 infusion versus Day 71 IV Push
Safety of Trogarzo given as an intramuscular injection in the Intramuscular Injection Group	Percent of subjects in Intramuscular Injection Group who complete 100% of all Trogarzo administrations given as infusion/bolus/push as per protocol	10 weeks
Pharmacokinetics(1) of Trogarzo infusion versus intramuscular injection in the Intramuscular Injection Group	Ratio of Area Under the Curve of Serum levels of Trogarzo given by 15 minute infusion versus Area Under the Curve of Serum levels of Trogarzo given by intramuscular injection	Day 1 infusion versus Day 71 intramusuclar injection
Pharmacokinetics(2) of Trogarzo infusion versus intramuscular injection in the Intramuscular Injection Group	Ratio of Trough Serum levels of Trogarzo given by 15 minute infusion versus Trough Serum levels of Trogarzo given by intramuscular injection	Day 1 infusion versus Day 71 intramusuclar injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of subjects in the Sentinel Group who fail to maintain virologic control	Percent of subjects in the Sentinel group who experience a sustained increase in log HIV-1 RNA levels of greater than 0.5log from baseline	99 days
Percent of HIV-infected subjects in the Core Group who fail to maintain virologic control	Percent of subjects in the Core group who experience a sustained increase in log HIV-1 RNA levels of greater than 0.5log from baseline	84 days
Percent of HIV-infected subjects in the Intramuscular Injection Group who fail to maintain virologic control	Percent of HIV-infected subjects in the Intramuscular Injection Group who experience a sustained increase in log HIV-1 RNA levels of greater than 0.5log from baseline	84 days

Collaborators and Investigators

• Sponsor: TaiMed Biologics Inc.
• Collaborators: Westat
• Investigators: Study Chair: Martin Markowitz, MD, TaiMed Biologics Inc. - Consultant

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2019
• Primary Completion (Actual): October 17, 2022
• Study Completion (Actual): October 31, 2022

Study Registration Dates

• First Submitted: April 9, 2019
• First Submitted That Met QC Criteria: April 10, 2019
• First Posted (Actual): April 12, 2019

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 14, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: HIV; ibalizumab; MDR HIV
• Additional Relevant MeSH Terms: Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Ibalizumab
• Other Study ID Numbers: TMB-302

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD will not be shared with other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No