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Drug Trials Snapshots: AKLIEF

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 AKLIEF Package Insert for complete information.

AKLIEF (trifarotene)
ack-LEEF
Galderma Laboratories
Approval date: October 4, 2019


DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

AKLIEF is a drug used on the skin to treat acne vulgaris in patients 9 years and older.

Acne vulgaris is a skin disease characterized by blackheads, whiteheads, pimples, and sometimes oily skin and scarring.

How is this drug used?

AKLIEF is a cream applied to the affected skin of face and/or trunk once a day, in the evening.

What are the benefits of this drug?

More patients achieved a reduction in the number of acnes and clear or almost clear skin after 12 weeks of treatment with AKLIEF cream in comparison to those who were treated with placebo cream.

What are the benefits of this drug (results of trials used to assess efficacy)?

The table below summarizes efficacy results for the evaluated patients in Trials 1 and 2. The co-primary endpoints were the percentage of patients with Investigator’s Global Assessment (IGA) score of clear (0) or almost clear (1) and 2-point decrease from baseline and the absolute reduction from baseline in inflammatory and non-inflammatory lesion counts at week 12.

Table 2. Acne of the Face Efficacy Results at Week 12 (Intent-to-Treat; Multiple Imputation)

 

Trial 1

Trial 2

AKLIEF Cream

Vehicle Cream

AKLIEF Cream

Vehicle Cream

(N= 612)

(N= 596)

(N= 602)

(N=610)

IGA Success
At least a 2-grade
improvement and “Clear” (0)
or “Almost Clear” (1)

29.4%

19.5%

 42.3%

 25.7%

Inflammatory Lesions
Mean* Absolute (Percent) Change from Baseline

 

-19.0 (-54.4%)

 

-15.4 (-44.8%)

 

-24.2 (-66.2%)

 

-18.7 (-51.2%)

Non-inflammatory Lesions
Mean* Absolute (Percent) Change from Baseline

 

-25.0 (-49.7%)

 

-17.9 (-35.7%)

 

-30.1 (-57.7%)

 

-21.6 (-43.9%)

*Means presented in table are Least Square (LS) means

Table 3. Acne of the Trunk Efficacy Results at Week 12 (Intent-to-Treat on the Trunk; Multiple Imputation)

 

Trial 1

Trial 2

 

AKLIEF Cream

Vehicle Cream

AKLIEF Cream

Vehicle Cream

(N= 600)

(N=585)

(N= 598)

(N=609)

PGA Success
At least a 2-grade improvement and “Clear” (0) or “Almost Clear” (1)

35.7%

25.0%

42.6%

29.9%

Inflammatory Lesions
Mean* Absolute (Percent) Change from Baseline

-21.4 (-57.4%)

-18.8 (-50.0%)

-25.5 (-65.4%)

 

-19.8 (-51.1%)

 

Non-Inflammatory Lesions
Mean* Absolute (Percent) Change from Baseline

 

-21.9 (-49.1%)

 

-17.8 (-40.3%)

 

-25.9 (-55.2%)

 

 

-20.8 (-45.1%)

 

*Means presented in table are Least Square (LS) means

AKLIEF Prescribing Information

Were there any differences in how well the drug worked in clinical trials among sex, race and age?

  • Sex: AKLIEF worked similarly in males and females.
  • Race: AKLIEF worked similarly among tested races.
  • Age: AKLIEF worked similarly between patients younger and older than 18 years of age.

Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?

The figures below summarize efficacy results by sex, race, and age based on IGA endpoint.

Figure 4. IGA Treatment Effects at Week 12 by Demographic Subgroups Trial 1

 

Figure 5. IGA Treatment Effects at Week 12 by Demographic Subgroups Trial 2

A=AKLIEF; V=vehicle

FDA Review

 

What are the possible side effects?

The most common side effects of AKLIEF are application site reactions (irritation and itching), and sunburn. Sometimes, these side effects could be severe.

Patients are advised to minimize sunlight and ultraviolent light exposure.

What are the possible side effects (results of trials used to assess safety)?

Adverse reactions reported in the 2 randomized, double-blind, vehicle-controlled 12-week clinical trials are presented in Table 4.

Table 4. Adverse Reactions Occurring in ≥ 1.0% of Patients with Acne Vulgaris in the Face and Trunk in the Two 12 week Phase 3 Clinical Trials

Preferred Term

AKLIEF Cream 

(N= 1220)

Vehicle Cream

(N=1200)

Application site irritation

91 (7.5)

 4 (0.3)

Application site pruritus

29 (2.4)

10 (0.8)

Sunburn

 32 (2.6)

6 (0.5)

 
In the open-label, 1-year trial, the local tolerability profile was comparable to that observed in the two pivotal Phase 3 trials.


AKLIEF Prescribing Information

Were there any differences in side effects among sex, race and age?

  • Sex: The occurrence of side effects was similar among males and females.
  • Race: The occurrence of side effects was similar among tested races.
  • Age: The occurrence of side effects was similar between patients younger and older than 18 years of age.

Were there any differences in side effects of the clinical trials among sex, race, and age groups?

The table below summarizes the occurrence of the most common adverse reaction-application site irritation-by subgroup.

Table 5. Subgroup Analysis of Application Site Irritation

Demographic Characteristic

AKLIEF
n/N (%)

Vechicle
n/N (%)

Sex

  Male

34/555 (6)

1/541 (<1)

  Female

45/665 (7)

1/659 (<1)

Race

   White

67/1078 (6)

2/1033 (<1)

   Black or African American

5/74 (7)

0/91 (0)

   Asian

3/25 (12)

0/38 (0)

  Other

4/43 (9)

0/38 (0)

Age Group

  < 18 years

44/594 (7)

1/568 (<1)

  > 18 years

35/626 (6)

1/632 (<1)

Adapted from FDA Review

WHO WAS IN THE CLINICAL TRIAL?

Who participated in the clinical trials?

The FDA approved AKLIEF based primarily on evidence from two clinical trials (Trial 1/NCT02566369 and Trial 2/NCT02556788) of 2420 patients with moderate acne vulgaris on the face and/or trunk. The trials were conducted at 198 sites in the United States, Canada, Puerto Rico and Europe.

Demographics of these two trials are presented in Figures 1-3 below and in in Table 6 under MORE INFO.

One additional trial of 453 patients with moderate acne vulgaris on the face and/or trunk assessed the side effects when AKLIEF was used for one year. Demographics of that trial is presented separately in Table 7 under MORE INFO.

Figure 1 summarizes how many males and females were in the clinical trials 1 and 2.

Baseline Demographics by Sex

FDA Review

Figure 2 summarizes the percentage of patients by race in the clinical trials 1 and 2.

Figure 2. Baseline Demographics by Race

*Other includes American Indian or Alaska Native, Missing

FDA Review

Table 1. Demographics of Trials 1 and 2 by Race

Race

Number of Patients

Percentage of Patients

White

2111

87

Black or African American

165

7

Asian

63

3

American Indian or Alaska Native

19

1

Native Hawaiian or Other Pacific Islander

3

Less than 1

Multiple

22

1

Other

37

1

FDA Review

Figure 3 summarizes the percentage of patients by age in the clinical trials 1 and 2.

Figure 3. Baseline Demographics by Age

FDA Review

Who participated in the trials?

Presented below are safety populations from pooled Trials 1 and 2 and from Trial 3, respectively.

Table 6. Demographics of Pooled Trials 1 and 2 (safety population)

Demographic Characteristic

AKLIEF N=1220
n (%)

Vechicle
N=1200
n (%)

TOTAL
N=2420
n (%)

Sex

 

  Male

555 (45.5)

541 (45.1)

1096 (45.3)

  Female

665 (54.5)

659 (54.9)

1324 (54.7)

Race

 

   White

1078 (88.4)

1033 (86.1)

2111(87.2)

   Black or African American

74 (6.1)

91 (7.6)

165 (6.8)

   Asian

25 (2)

38 (3.2)

63 (2.6)

  American Indian or Alaska Native

12 (1)

7 (0.6)

19 (0.8)

  Native Hawaiian or Other Pacific Islander

1 (0.1)

2 (0.2)

3 (0.1)

  Multiple

11 (0.9)

11 (0.9)

22 (0.9)

  Other

19 (1.6)

18 (1.5)

37 (1.5)

Age (years)

  Median

18

18

18

  Min, Max

9,58

10,50

9,58

Age Group (years)

  9-11

19 (1.6)

15 (1.3)

34 (1.4)

  12-17

575 (47.1)

553 (46.1)

1128 (46.6)

    ≥18

626 (51.3)

632 (52.7)

1258 (52)

Ethnicity

  Hispanic or Latino

195 (16)

210 (17.5)

405 (16.7)

  Not Hispanic or Latino

1025 (84)

990 (82.5)

2015 (83.3)

Geographic Region

   US

531 (43.5)

549 (45.8)

1080 (44.6)

   Canada

70 (5.7)

69 (5.8)

139 (5.7)

   Puerto Rico

27 (2.2)

28 (2.3)

55 (2.3)

   Europe

592 (48.5)

554 (46.2)

1146 (47.4)

Clinical Trial Data

Table 7. Demographics of Trial 3 (Long Term Safety Trial)

Demographic Characteristic

AKLIEF
N=453
n (%)

Sex

  Male

227 (50.1)

  Female

226 (49.9)

Race

   White

432 (95.4)

   Black or African American

12 (2.6)

   Asian

3 (0.7)

  American Indian or Alaska Native

1 (0.2)

   Native Hawaiian or Other Pacific         Islander

3 (0.7)

   Multiple

2 (0.4)

  Other

0

Age (years)

  Median

16

  Min, Max

9,54

Age Group (years)

  9-11

18 (4)

  12-17

268 (59.2)

  ≥18

167 (36.9)

Ethnicity

    Hispanic or Latino

47 (10.4)

    Not Hispanic or Latino

406 (89.6)

Geographic Region

     US

163 (36)

     Europe

290 (64)

Clinical Trial Data

How were the trials designed?

There were three trials that were used to approve AKLIEF for treatment of acne in patients 9 years and older.

Trials 1 and 2 enrolled patients 9 years of age and older with moderate facial and truncal acne vulgaris. Approximately half of all patients applied AKLIEF cream and the other half applied placebo cream once daily (at night) for 12 weeks. Neither the patients nor the health care providers knew which treatment was being given until after the trial was completed. The benefit of AKLIEF in comparison to placebo was assessed after 12 weeks of treatment using the Investigator’s Global Assessment (IGA) score that measures the severity of disease (on a scale from 0 to 4) and a decrease in the number of pimples.

Trial 3 enrolled patients 9 years and older with moderate facial and/or truncal acne vulgaris. Patients received AKLIEF cream once daily for one year. Patients in Trial 3 were primarily evaluated for side effects.

How were the trials designed?

There were three trials that were used to approve AKLIEF for treatment of acne in patients 9 years and older.

Trials 1 and 2 were randomized, double-blind, placebo-controlled clinical trials designed to evaluate AKLIEF in patients 9 years and older with moderate facial and truncal acne. Patients were randomized to receive either AKLIEF or vehicle cream once daily for 12 weeks. The co-primary efficacy endpoints were the percentage of patients with Investigator’s Global Assessment (IGA) success and the absolute reduction from baseline in inflammatory and non-inflammatory lesion counts at week 12. IGA success was defined as a score of clear (0) or almost clear (1) and a 2-point decrease from baseline on IGA score at week 12.

Trial 3 was an open-label safety trial of one-year duration that included patients 9 years and older, with acne vulgaris of the face and trunk. Patients received AKLIEF cream once a day and were evaluated for long term adverse events.

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.

PRESCRIBING INFORMATION

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