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

• ClinicalTrials.gov Identifier: NCT03913195
• Recruitment Status: Recruiting
• First Posted: April 12, 2019
• Last Update Posted: June 13, 2019
• Sponsor: TaiMed Biologics Inc.
• Collaborator: Westat
• Information provided by (Responsible Party): TaiMed Biologics Inc.

Tracking Information

• First Submitted Date: April 9, 2019
• First Posted Date: April 12, 2019
• Last Update Posted Date: June 13, 2019
• Actual Study Start Date: May 30, 2019
• Estimated Primary Completion Date: May 15, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 11, 2019)

• Safety of Trogarzo given as IV Push over 30 seconds in Sentinel Group [ Time Frame: 12 weeks ]
  Percent of subjects in Sentinel Group who complete 100% of all Trogarzo administrations given as infusion/bolus/push as per protocol
• Safety of Trogarzo given as IV Push over 30 seconds in Core Group [ Time Frame: 10 weeks ]
  Percent of subjects in Core Group who complete 100% of all Trogarzo administrations given as infusion/bolus/push as per protocol
• Pharmacokinetics(1) of Trogarzo infusion versus IV Push in Sentinel Group [ Time Frame: Day 1 infusion versus Day 85 IV Push ]
  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
• Pharmacokinetics(2) of Trogarzo infusion versus IV Push in Sentinel Group [ Time Frame: Day 1 infusion versus Day 85 IV Push ]
  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
• Pharmacokinetics(1) of Trogarzo infusion versus IV Push in Core Group [ Time Frame: Day 1 infusion versus Day 71 IV Push ]
  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
• Pharmacokinetics(2) of Trogarzo infusion versus IV Push in Core Group [ Time Frame: Day 1 infusion versus Day 71 IV Push ]
  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

Original Primary Outcome Measures (submitted: April 10, 2019)

• Safety of Trogarzo given as IV Push over 30 seconds in Sentinal Group [ Time Frame: 12 weeks ]
  Percent of subjects in Sentinel Group who complete 100% of all Trogarzo administrations given as infusion/bolus/push as per protocol
• Safety of Trogarzo given as IV Push over 30 seconds in Core Group [ Time Frame: 10 weeks ]
  Percent of subjects in Sentinel Group who complete 100% of all Trogarzo Percent of subjects in Sentinel Group who complete 100% of all Trogarzo administrations given as infusion/bolus/push as per protocol
• Pharmacokinetics(1) of Trogarzo infusion versus IV Push in Sentinel Group [ Time Frame: Day 1 infusion versus Day 85 IV Push ]
  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
• Pharmacokinetics(2) of Trogarzo infusion versus IV Push in Sentinel Group [ Time Frame: Day 1 infusion versus Day 85 IV Push ]
  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
• Pharmacokinetics(1) of Trogarzo infusion versus IV Push in Core Group [ Time Frame: Day 1 infusion versus Day 71 IV Push ]
  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
• Pharmacokinetics(2) of Trogarzo infusion versus IV Push in Core Group [ Time Frame: Day 1 infusion versus Day 71 IV Push ]
  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

• Change History: Complete list of historical versions of study NCT03913195 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: April 11, 2019)

• Percent of subjects in the Sentinel Group who fail to maintain virologic control [ Time Frame: 99 days ]
  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
• Percent of subjects in the Core Group who fail to maintain virologic control [ Time Frame: 84 days ]
  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

Original Secondary Outcome Measures (submitted: April 10, 2019)

• Percent of subjects in the Sentinel Group who fail to maintain virology control [ Time Frame: 99 days ]
  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
• Percent of subjects in the Core Group who fail to maintain virology control [ Time Frame: 84 days ]
  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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of the Safety of Trogarzo™ Administered as an Undiluted "IV Push"
• Official Title: A Phase 3 Study of the Safety of Trogarzo™ Administered as an Undiluted "IV Push" Over a Reduced Interval in Clinically Stable HIV-1 Infected Trogarzo™ Experienced Patients
• Brief Summary: This study is designed to assess the safety and pharmacokinetic profile of 800 mg Trogarzo once every two weeks administered via "IV Push". 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.

Detailed Description

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

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. 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, Core Group participants will receive the prescribed dosage of Trogarzo via undiluted IV Push over 30 seconds through Day 71 of the study.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: HIV-1-infection

Intervention

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 Name: Trogarzo

Study Arms

• 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.
  Intervention: Drug: ibalizumab-uiyk
• Experimental: Core Group
  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.
  Intervention: Drug: ibalizumab-uiyk

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 10, 2019): 20
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 15, 2020
• Estimated Primary Completion Date: May 15, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

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

Exclusion Criteria:

1. Any active AIDS-defining illness according to the Centers for Disease Control and Prevention (CDC) Revised Surveillance Case Definitions for HIV Infection 2008 (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 patient 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, patients 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 patient 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 patient'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 grading scale, except for the following asymptomatic Grade 3 events:

    • triglyceride elevation
    • total cholesterol elevation any Grade 3 or 4 reduction in CD4+ T cell counts

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Tracy Wolbach; 240-453-2658; tracywolbach@westat.com

Contact: Christine Anderson, PhD; 713-353-7911; christineanderson@westat.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03913195
• Other Study ID Numbers: TMB-302
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: IPD will not be shared with other researchers.

• Responsible Party: TaiMed Biologics Inc.
• Study Sponsor: TaiMed Biologics Inc.
• Collaborators: Westat

Investigators

• Study Chair: Martin Markowitz, MD; TaiMed Biologics Inc. - Consultant

• PRS Account: TaiMed Biologics Inc.
• Verification Date: June 2019