Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT05322941 |
| Other study ID # |
AEF0117-202 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
May 6, 2022 |
| Est. completion date |
May 2024 |
Study information
| Verified date |
April 2024 |
| Source |
Aelis Farma |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Cannabis use is increasing and will only further escalate with legalization of recreational
and medical cannabis use in western countries , with a prevalence greater than 30 % in the US
and most European countries for individuals between 16 and 24 years of age. Approximately 9 %
of those who use cannabis will become addicted. The number goes up to about 1 in 6 among
those who start using cannabis as teenagers and to 25 to 50 % among those who smoke cannabis
daily. The consequences of cannabis abuse in the most prone population (14-25 years of age)
are extremely serious, and may include addiction, altered brain development, poorer
educational outcomes, cognitive impairment, lower income, greater welfare dependence,
unemployment and lower relationship and life satisfaction. There are no available
pharmacological treatments of cannabis use disorder (CUD). Thus, the development of safe and
effective medications for the treatment of CUD is an urgent public health priority.
The preclinical efficacy and available ADMET (Administration, Distribution, Metabolism,
Elimination and Toxicology) in animal and human data suggest that AEF0117, an investigational
new study drug, could constitute a very efficacious and safe treatment for cannabis abuse
disorders. The purpose of this research is to study how AEF0117 influences the subjective
effects of cannabis in subjects with CUD. AEF0117 acts in the same parts of the brain as THC
(tetrahydrocannabinol), the active ingredient of marijuana, and may temporarily alter some of
cannabis's effects.
The safety and tolerability of AE0117 has been demonstrated in the clinical studies conducted
to date. This study will provide additional data on the efficacy of AEF0117 on
treatment-seeking subjects with moderate to severe CUD.
This is a phase 2b, randomized, double-blind, placebo-controlled, 4-arm, parallel-group,
prospective, multicenter study. The overall purpose of this study is to assess the efficacy
and safety of AEF0117 in subjects with moderate to severe CUD who are treatment-seeking. The
primary objective of this study is to demonstrate that AEF0117 induces a greater proportion
of RESPONDERS (i.e., subjects with a RESPONSE of ≤1 day of cannabis use per week) compared to
placebo in treatment-seeking subjects with moderate to severe CUD, according to DSM-5
criteria.The secondary objectives are to investigate the proportion of subjects that reach
various levels of reduction and how this influences their quality of life, and to evaluate
the safety and tolerability of AEF0117. And the exploratory objectives of this study are to
further evaluate the effect of AEF0117 on pattern of cannabis use and change in various signs
and symptoms, and in addition to assess effects during the grace period and the entire
treatment period.
Description:
Cannabis use is increasing and will only further escalate with legalization of recreational
and medical cannabis use in western countries , with a prevalence greater than 30 % in the US
and most European countries for individuals between 16 and 24 years of age. Approximately 9 %
of those who use cannabis will become addicted. The number goes up to about 1 in 6 among
those who start using cannabis as teenagers and to 25 to 50 % among those who smoke cannabis
daily. The consequences of cannabis abuse in the most prone population (14-25 years of age)
are extremely serious, and may include addiction, altered brain development, poorer
educational outcomes, cognitive impairment, lower income, greater welfare dependence,
unemployment and lower relationship and life satisfaction. There are no available
pharmacological treatments of cannabis use disorder (CUD). Thus, the development of safe and
effective medications for the treatment of CUD is an urgent public health priority.
The preclinical efficacy and available ADMET (Administration, Distribution, Metabolism,
Elimination and Toxicology) in animal and human data suggest that AEF0117, an investigational
new study drug, could constitute a very efficacious and safe treatment for cannabis abuse
disorders. The purpose of this research is to study how AEF0117 influences the subjective
effects of cannabis in subjects with CUD. AEF0117 acts in the same parts of the brain as THC
(tetrahydrocannabinol), the active ingredient of marijuana, and may temporarily alter some of
cannabis's effects.
The safety and tolerability of AE0117 has been demonstrated in the clinical studies conducted
to date. This study will provide additional data on the efficacy of AEF0117 on
treatment-seeking subjects with moderate to severe CUD.
This will be a phase 2b, randomized, double-blind, placebo-controlled, 4-arm, parallel-group,
prospective, multicenter study. The overall purpose of this study is to assess the efficacy
and safety of AEF0117 in subjects with moderate to severe CUD who are treatment-seeking. The
overall purpose of this study is to assess the efficacy and safety of AEF0117 in subjects
with moderate to severe CUD who are treatment-seeking.
Up to 330 eligible male or female subjects will be randomized into 1 of 4 treatment groups.
Due to the difference in prevalence of CUD between males and females, the number of females
enrolled is anticipated to be less than 1/3 of all subjects. Moreover, the number of female
subjects to be enrolled will be limited via stratification ensuring that a maximum 80 females
will be assigned to active treatment (i.e., to 1 of the AEF0117 treatment groups),
considering the development stage of the compound.
Subjects will be randomized to 1 of 4 treatment groups:
- AEF0117 1.0 mg once daily (QD) (90 subjects)
- AEF0117 0.3 mg QD (90 subjects)
- AEF0117 0.1 mg QD (60 subjects)
- Placebo QD (90 subjects)
The primary objective of this study is to demonstrate that AEF0117 induces a greater
proportion of RESPONDERS (i.e., subjects with a RESPONSE of ≤1 day of cannabis use per week)
compared to placebo in treatment-seeking subjects with moderate to severe CUD, according to
DSM-5 criteria.
The secondary objectives are to investigate the proportion of subjects that reach various
levels of reduction and how this influences their quality of life, and to evaluate the safety
and tolerability of AEF0117.
- Assess if AEF0117 increases the proportion of subjects that reach complete abstinence (0
cannabis use).
- Assess if AEF0117 increases the proportion of subjects that have a modest level of
cannabis use (≤2 days per week).
- Assess if AEF0117 increases the proportion of subjects that report no CUD symptoms
according to DSM-5 except for craving (modified early remission, which is defined by the
same criteria of the DSM-5 but without the required minimal time duration of the
remission).
- Assess if AEF0117 decreases the percentage of days of cannabis use.
- Assess if AEF0117 improves the quality of life as measured by the Patient-Reported
Outcomes Measurement Information System-29 (PROMIS-29) adult profile.
- Assess if AEF0117 introduce a change in pattern of cannabis use over the day.
- Assess the safety and tolerability of AEF0117.
The exploratory objectives of this study are to further evaluate the effect of AEF0117 on
pattern of cannabis use and change in various signs and symptoms, and in addition to assess
effects during the grace period and the entire treatment period.
The study consists of a screening period, a double-blind treatment period which includes a
grace period and a treatment ascertainment period, and a follow-up period. The study will be
conducted on an outpatient basis at the sites with a total of 27 visits per subject after
screening for eligibility. During the 12-week treatment period, 25 visits will be performed:
1 weekly visit will include most of the scheduled assessments (13 full visits), while the
second weekly visit will only include few assessments (12 short visits).Under certain
circumstances, a short visit may be converted to a remote visit if it does not pose a risk to
the safety of the subject as judged by the investigator.
During the 4-week follow-up period, 2 visits approximately 14 days apart will take place.
The double-blind randomized treatment period will consist of 2 periods: a 4-week grace period
and an 8-week treatment ascertainment period. During both periods, subjects will attend
standardized medical management sessions once a week with trained professionals (i.e., 12
visits in total).
During the grace period (Day 1 to Day 28), cannabis use will not be a criterion for
characterization of non-responding subjects. This period will allow AEF0117 to reach plasma
steady state and allow for behavioral changes. During the treatment ascertainment period (Day
29 to Day 84), any cannabis use will be taken into consideration to assign subjects as
responders and non-responders.
All study visits will be conducted on an outpatient basis at the sites. Screening visit(s),
weekly full visits during the grace period and treatment ascertainment period (13 visits) and
visits every second week during follow up (2 visits) include extended assessments. In
addition, 1 short visit per week is scheduled during the grace period and treatment
ascertainment period (12 visits), including a few assessments (the second of the twice weekly
visits).
Efficacy will be assessed using different observer-rated and self-reported scales.
Self-reported cannabis use will be monitored daily, prospectively by an Ecological Momentary
Assessment (EMA) using a smartphone-based application and retrospectively by using the TLFB
procedure.
The documentation of self-reported cannabis use will be based primarily on the EMA data and,
in the case of missing data, on the TLFB data. In the case of a discrepancy, the more
conservative data will be used (i.e., presence of an episode of use).
Adverse events will be monitored by research staff and medical observations and spontaneous
reporting throughout the study. The grading system of adverse events used in this study will
be the grading system proposed by Sibille M., et. al. Specifications on the grading system
for clinical observations and ECG parameters will be based on the publication by Sibille M,
Patat A, et al. Vital signs and laboratory parameters will be based on the FDA vaccine
guidance (The Biologics Blood Vaccines Guidance Compliance, FDA).
