Drug Trials Snapshots: TROGARZO
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the clinical trials that supported the FDA approval of this drug, and whether there were differences among sex, race and age groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your health provider about the risks and benefits of a drug. Refer to the TROGARZO Package Insert for complete information.
TROGARZO (ibalizumab-uiyk)
(tro-gar-zo)
Thera
Approval date: March 6, 2018
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
TROGARZO is a drug for the treatment of human immunodeficiency virus 1 (HIV-1) infection in adults who:
- have received several anti-HIV-1 regimens in the past, and
- have HIV-1 virus that is not responding to many antiretroviral medicines, and
- who are failing their current antiretroviral therapy
HIV-1 is the virus that causes AIDS (Acquired Immune Deficiency Syndrome).
How is this drug used?
TROGARZO is used in combination with other antiretroviral medications.
TROGARZO is is given by a health care professional once every two weeks directly into the bloodstream through a needle in the vein. This is known as an intravenous, or IV infusion. It takes 15-30 minutes to receive TROGARZO infusion.
What are the benefits of this drug?
In the trial, 33 of the 40 patients (83%) treated with TROGARZO experienced a significant decrease in their HIV-RNA levels one week after TROGARZO was added to their failing antiretroviral regimens.
After 24 weeks of TROGARZO treatment (in combination with other antiretroviral drugs), 43 % of the patients achieved HIV RNA suppression.
What are the benefits of this drug (results of trials used to assess efficacy)?
The primary efficacy endpoint was the proportion of patients achieving a ≥ 0.5 log10 decrease in viral load from the beginning to the end of the “Functional monotherapy period” as compared to the proportion of subjects achieving a ≥ 0.5 log10 decrease from the beginning to the end of the “Control” period.
Table 2. Proportion of Subjects Achieving a ≥ 0.5 log10 Decrease in Viral Load at the End of the Control and Functional Monotherapy Periods
|
|
Proportion of Subjects Achieving a ≥ 0.5 |
95% CI* |
|
End of Control Period |
3% |
(0.06%, 13%) |
|
End of Functional |
83% |
(67%, 93%) |
*exact 95% confidence interval
p < 0.0001="" based="" on="" mcnemar’s="" test="" comparing="" the="" proportion="" of="" subjects="" achieving="" ≥="" 0.5="" log10="" decrease="" in="" viral="" load="" at="" the="" end="" of="" the="" control="" and="" functional="" monotherapy="">
At Week 25, viral load <50 and=""><200 hiv-1="" rna="" copies/ml="" was="" achieved="" in="" 43%="" and="" 50%="" of="" patients,="">
TROGARZO Prescribing Information
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
The trial was too small to determine the differences among sex, race and age subgroups.
Were there any differences in how well the drug worked in clinical trials among sex, race and age groups?
Table below summarizes the subgroup analysis by demographics for primary efficacy endpoint in ITT population. This analysis is limited by the small sample size.
Table 3. Percentage of Patients Achieving a ≥ 0.5 log10 Decrease from Day 7 to Day 14
| %(n/N) | [95% CI] | |
|---|---|---|
| Sex | ||
| Men | 79.4% (27/34) | [62.1%, 91.3%] |
| Women | 100% (6/6) | [54.1%, 100%] |
| Race | ||
| White | 81.8% (18/22) | [59.7%, 94.8%] |
| Asian | 100% (4/4) | [39.8%, 100%] |
| All Other | 78.6% (11/14) | [49.2%, 95.3%] |
| Age | ||
| < 50=""> | 92.3% (12/13) | [64.0%, 99.8%] |
| ≥ 50 years | 77.8% (21/27) | [57.7%, 91.4%] |
Adapted from Clinical Study report
What are the possible side effects?
During the initial phase of treatment with TROGARZO, the immune system may get stronger and begin to fight infections that were hidden (a condition called immune reconstitution syndrome). Immune reconstitution syndrome is a serious condition.
The most common side effects of TROGARZO include diarrhea, dizziness, nausea, and rash.
What are the possible side effects (results of trials used to assess safety)?
The summary of adverse reaction from the trial is presented below.
Table 4. Adverse Reactions (All Grades) Reported in ≥ 5% of Patients Receiving TROGARZO and Optimized Background Regimen for 23 Weeks in Trial TMB-301
|
|
% Patients |
|---|---|
|
Diarrhea |
8% |
|
Dizziness |
8% |
|
Nausea |
5% |
|
Rash* |
5% |
*Includes pooled terms “rash”, “rash erythematous”, “rash generalized”, “rash macular”, “rash maculopapular”, and “rash papular”
TROGARZO Prescribing Information
Were there any differences in side effects among sex, race and age?
The trial was too small to determine differences in side effects among sex, race and age subgroups.
Were there any differences in side effects of the clinical trials among sex, race and age groups?
Table below summarizes adverse reactions occurring in two or more patients by sex, race, and ethnicity. This analysis is limited by the small sample size.
Table 5. Subgroub Analysis of Adverse Reactions
| Preferred Term |
Overall N=40 |
Sex | Age (years) | Race | Ethnicity | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| Men n=34 |
Women n=6 |
<50> n=13 |
≥50 n=27 |
White n=22 |
Black/AA n=13 |
Asian n=4 |
Hispanic n=10 |
Not Hispanic n=30 |
||
| Diarrhea | 3 (8%) | 3 (9%) |
0 | 1 (7%) |
2 (7%) |
2 (9%) |
0 | 1 (25%) |
0 | 3 (10%) |
| Nausea | 2 (5%) | 2 (6%) |
0 | 2 (15%) |
0 | 1 (5%) |
0 | 1 (25%) |
1 (10%) |
1 (3%) |
| Rash | 2 (5%) | 2 (6%) |
0 | 0 | 2 (7%) |
2 (9%) |
0 | 0 | 1 (10%) |
1 (3%) |
| Dizziness | 3 (8%) | 3 (9%) |
0 | 1 (7%) |
2 (7%) |
3 (14%) |
0 | 0 | 1 (10%) |
2 (7%) |
* “rash” represents several PTs, all of which are specific descriptions of types of rashes
Adapted from FDA Clinical review
WHO WAS IN THE CLINICAL TRIALS?
Who participated in the clinical trials?
The FDA approved TROGARZO based on evidence from one clinical trial (NCT02475629) of 40 adult patients with HIV-1 infection who did not respond to various anti-HIV treatments anymore.
The trial was conducted in the United States and Taiwan.
Figures 1, 2, and 3 summarize how many patients participated in the clinical trial by sex, race and age.
Figure 1. Baseline Demographics by Sex
FDA review
Figure 2. Baseline Demographics by Race
FDA review
Table 1. Baseline Demographics by Race
|
Race |
Number of Patients |
Percentage |
|---|---|---|
|
White |
22 |
55 |
|
Black or African American |
13 |
32 |
|
Asian |
4 |
10 |
|
Not reported |
1 |
3 |
FDA review
Figure 3. Baseline Demographics by Age
FDA review
Who participated in the trials?
The demographics from clinical trial of 40 adults with HIV-1 infection is presented below.
Table 6. Trial Demographics
| Demographic Parameter | Number of Patients Total N=40 n (%) |
|---|---|
| Sex | |
| Men | 34 (85) |
| Women | 6 (15) |
| Race | |
| White | 22 (55) |
| Black or African American | 13 (32.5) |
| Asian | 4 (10) |
| Not reported | 1 (2.5) |
| Ethnicity | |
| Hispanic | 10 (25) |
| Not Hispanic | 30 (75) |
| Age (years) | |
| Mean (SD) | 50.45 (10.9) |
| Median | 53 |
| Min, max | 23-65 |
| Age group | |
| ≥18 - 49 years | 13 (32.5%) |
| ≥ 50 years | 27 (67.5%) |
| ≥ 65 years | 2 (5) |
| Geographic region | |
| United States | 36 (90) |
| Taiwan | 4 (10) |
FDA review
How were the trials designed?
The benefits and side effects of TROGARZO were studied in one clinical trial that enrolled patients with HIV-1 infection who did not respond to various anti-HIV treatments anymore.
The trial consisted of three periods:
- An observation period from Day 0 to Day 6, during which patients continued their old therapy
- A therapy period from Day 7 to Day 13, during which patients received TROGARZO and continued their old therapy, and
- A maintenance period from Day 14 to Week 25 during which patients received lower dose of TROGARZO plus other anti-HIV drugs
The benefit of TROGARZO was assessed by measuring the number of HIV-1 copies in the blood from Day 7 to Day 14.
The efficacy and safety of TROGARZO were evaluated in a single-arm, multicenter trial in adult patients with multi-drug resistant HIV-1 infection.
The trial consisted of three periods:
- Control period (Day 0 to Day 6): Patients continued their failing antiretroviral therapy. This was an observational period to establish baseline HIV viral load.
- Functional Monotherapy Period (Day 7 to Day 13): Patients were treated with TROGARZO while continuing their failing antiretroviral therapy. This period was to establish the virologic activity of TROGARZO.
- Maintenance period (Day 14 to Week 25): TROGARZO was continued and an optimized background regimen was started for each patient. This period was to establish the safety and durability of virologic suppression of TROGARZO when used in combination with an optimized background regimen.
The primary efficacy endpoint was the percentage of subjects achieving a ≥ 0.5 log10 reduction in HIV RNA from Day 7 to Day 14.
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.