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Effect of AEF0117 on Treatment-seeking Patients With Cannabis Use Disorder (CUD): SICA 2: SPECIFIC SIGNALING INHIBITOR IN CANNABIS ADDICTION (SICA 2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05322941
Recruitment Status : Recruiting
First Posted : April 12, 2022
Last Update Posted : June 2, 2022
Sponsor:
Collaborator:
National Institute on Drug Abuse (NIDA)
Information provided by (Responsible Party):
Aelis Farma

Brief 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.


Condition or disease Intervention/treatment Phase
Marijuana Abuse Drug: AEF0117 Drug: Placebo oral capsule Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 330 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Up to 330 eligible male or female subjects will be randomized into 1 of 4 treatment groups. The number of females to be enrolled will be limited to ensure that a maximum of 80 female subjects are assigned to active treatment (i.e., to 1 of the AEF0117 treatment groups).

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 (90 subjects)
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Double-blind, Placebo-controlled, Randomized, Parallel-group, Phase 2b Study in Treatment-seeking Patients With Cannabis Use Disorder to Assess the Efficacy, Safety, and Tolerability of AEF0117 in Reducing Cannabis Use
Actual Study Start Date : May 6, 2022
Estimated Primary Completion Date : August 2023
Estimated Study Completion Date : November 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Marijuana

Arm Intervention/treatment
Experimental: AEF0117
The current study tests 3 doses of AEF0117 (1.0, 0.3, and 0.1 mg).AEF0117 capsules ; dose range 0.1 to 1.0mg by mouth, once a day for 12 weeks.
Drug: AEF0117
AEF0117 (1.0, 0.3, and 0.1 mg) capsules
Other Name: 3ß-(4-methoxybenzykoxy)pregn-5-en-20-one t)

Placebo Comparator: Placebo
corn oil capsules once a day for 12 weeks.
Drug: Placebo oral capsule
Corn oil capsule manufactured to mimic AEF0117 capsule




Primary Outcome Measures :
  1. Assessment of cannabis use [ Time Frame: up to 16 weeks (end of study) ]
    Cannabis use will be assessed using self-reporting and monitored daily, prospectively by an EMA using a smartphone-based application

  2. Assessment of cannabis use [ Time Frame: up to 16 weeks (end of study) ]
    Cannabis use will be assessed using self-reporting and monitored daily, by using the TLFB procedure at each visit. The TLFB will be used to corroborate data obtained with EMA evaluation of cannabis use.


Secondary Outcome Measures :
  1. Measures subject-rated intensity of withdrawal symptoms [ Time Frame: up to 16 weeks (end of study) ]
    The 19-item version of the Cannabis Withdrawal Scale (CWS) that will be used measures subject-rated intensity of withdrawal symptoms as well as the amount of distress or impairment in functioning due to each symptom for the last 24 hours on a scale of 0 ("not at all") to 10 ("extremely"). The following statements describe how you have felt over the last 24 hours

  2. Complete psychiatric diagnosis [ Time Frame: up to 16 weeks (end of study) ]
    The MINI International Neuropsychiatric Interview (MINI-5) will be used in order to complete psychiatric diagnostic assessment to assess for CUD criteria in addition to other psychiatric disorders for eligibility.

  3. Assesment of Quality of life [ Time Frame: up to 16 weeks (end of study) ]
    the Patient-Reported Outcomes Measurement Information System-29 is a 29-item self-report measure to assess quality of life by assessing functioning and well-being in physical, mental, and social domains of health over the last 7 days.


Other Outcome Measures:
  1. Assessment of Marijuana Craving [ Time Frame: up to 16 weeks (end of study) ]
    The Marijuana Craving Questionnaire-Short Form (MCQ-12) is a 12-item self-report measures subjects' craving for marijuana on a Likert scale of 1-7 and yields total scores and factor scores in the areas of compulsivity, emotionality, expectancy, and purposefulness.

  2. Assessment of Quality of sleep [ Time Frame: up to 16 weeks (end of study) ]
    The Medical Outcome Study - Sleep Scale (MOS-SS) is a 12-item measure for characterizing the quality of sleep over the past 4 weeks.

  3. Assessment of severity of nicotine dependence [ Time Frame: up to 16 weeks (end of study) ]
    The Fagerstrom Test for Nicotine Dependence is a 6 item self-report questionnaire assessing severity of nicotine dependence

  4. Assessment of desire to quit cannabis [ Time Frame: up to 16 weeks (end of study) ]
    the Motivation to Quit Ladder is a single item change ladder from 1 to 10, where 1 is "no desire to quit" and higher numbers are greater desire to quit



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female subjects between 18 and 65 years old, both inclusive.
  2. Subjects must meet DSM-5 criteria for moderate to severe CUD as assessed by the standard MINI-5.
  3. Subjects must be treatment-seeking and have a mean cannabis use of ≥5 days per week within the last 4 weeks at the screening and baseline visit of the study. Mean cannabis use is assessed by the TLFB and a positive urine concentration test (creatinine-normalized [THC-COOH] ≥50 ng/mL).
  4. Subjects must use inhalation (i.e., smoking, vaping) consistently as the primary route of cannabis administration. Additional use of edible cannabis is allowed.
  5. Written informed consent to participate in the study.
  6. Body mass index (BMI) between ≥18 and <35 kg/m2, inclusive, by Nomograph for BMI at screening.
  7. Female subjects of childbearing potential, defined as having a menstrual cycle that is confirmed prior to enrollment, and who are heterosexually active and not surgically sterile or at least 2 years postmenopausal, must agree to use one of the following forms of contraception throughout the study and until 21 days after the last dose of study drug: abstinence, hormonal (oral, transdermal, implant, or injection), barrier (condom, diaphragm with spermicide), intrauterine device, or vasectomized partner (6 months minimum).
  8. Male subjects are to refrain from donating sperm and heterosexually active male subjects must agree to the use of highly effective contraceptive methods (e.g., double barrier with at least condoms and spermicide) from screening through 90 days after the last dose of study drug, or their female partner must use a highly effective method of contraception as listed in inclusion criteria 7 from screening through 90 days after the last dose.
  9. No clinically significant abnormal findings in the medical history, on physical examination, ECG, or clinical laboratory results (see Appendix B) during screening that could jeopardize the safety of the subject or impact the validity of the study.
  10. Subjects must agree to return to the study site as required, be able to read English, and be willing to comply with all required study procedures.

Exclusion Criteria:

  1. A history of clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, psychiatric, or cardiovascular disease, or any other condition which, in the opinion of the principal investigator, would jeopardize the safety of the subject or impact the validity of the study results. For psychiatric disease, see more details below.
  2. Subject has had significant traumatic injury, major surgery, or open biopsy within 30 days prior to the screening visit.
  3. Presence or history within 12 months prior to screening of other substance use disorders according to DSM-5 criteria (as assessed by the MINI-5, psychiatric assessment, urine drug screen, breath analyzer, as appropriate) except for mild alcohol use disorder (as defined in DSM-5) or tobacco use disorder. Current use (within 30 days prior to screening) of opioid agonist or antagonist.
  4. Subjects meeting DSM-5 criteria for schizophrenia, schizoaffective illness, psychotic disorder other than transient psychosis due to drug abuse, bipolar illness, or psychiatric disorders (other than substance abuse).
  5. Subjects with major depression and a HAM-D >17, and subjects with a baseline CGI >4 for other psychiatric disorders. Subjects with major depression or other current psychiatric disorders, in whom stable control has not been obtained within the 3 months prior to screening (with either behavioral treatment or unchanged medication and dose). Subjects with a current psychiatric disorder treated with prohibited medications (e.g., benzodiazepines, antipsychotics, and anticonvulsants). Present psychiatric state as established by the MINI-5 (severity and change in symptoms will be measured by the Hamilton Anxiety [HAM-A] and Depression [HAM-D] Scales [14-item anxiety and 17-item depression] at start of and during the study).
  6. Subjects with a history of or current homicidal ideations or attempts.
  7. Subjects with a past suicide attempt within the past 2 years or any Suicidal Ideation of 3, 4, or 5 or any Suicidal Behavior in Lifetime using the Baseline/Screening version of the C-SSRS.
  8. Subjects who use daily supplements of steroids (or food containing steroids), including pregnenolone, during the 4 weeks prior to the first screening visit. Topical use of steroids is allowed, and hormonal contraceptives are allowed if using a stable regimen throughout the study.
  9. Subjects with frequent regular use of diet or supplements (e.g., St. John's Wort), food or grapefruit juice that may interfere with the activities of CYP P450.
  10. Participation in a clinical trial within 1 month prior to the first dose of study drug, or 2 months if terminal half-life of the investigational drug is more than 120 hours.
  11. Female subjects who are trying to conceive, are pregnant, are lactating or have a positive serum pregnancy test at screening or a positive urine pregnancy test at study visits, regardless of childbearing potential.
  12. A positive urine drug screen for other drugs of abuse other than cannabinoids and/or a positive breath test for alcohol. One repeat alcohol breath test is allowed at a second screening visit or at the baseline visit.
  13. Subjects with known allergy to corn or corn derivatives.
  14. Subjects under any administrative or legal supervision.
  15. Subjects taking any of the medications or substances

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05322941


Contacts
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Contact: Stephanie Monlezun +33 7 89 56 36 33 s.monlezun@aelisfarma.com
Contact: Frances Levin, MD +1 201-694-3565 Frances.Levin@nyspi.columbia.edu

Locations
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United States, California
UCLA Department of Psychiatry and Biobehavioral Sciences Not yet recruiting
Los Angeles, California, United States, 90095
Contact: Larissa Mooney, MD    310-794-1497    LMooney@mednet.ucla.edu   
United States, Connecticut
Yale Stress Center - Addiction Program Not yet recruiting
New Haven, Connecticut, United States, 06520
Contact: Rajita Sinha, MD    203-737-3436    rajita.sinha@yale.edu   
United States, Florida
Segal Trial Not yet recruiting
Lauderhill, Florida, United States, 33319
Contact: Richi Kakar, MD    954-990-6326    rkakar@segaltrials.com   
United States, New York
The Substance Treatment and Research Service (S.T.A.R.S.) of Columbia University/NYSPI. Not yet recruiting
New York, New York, United States, 10032
Contact: Frances Levin, MD    201-694-3565    Frances.Levin@nyspi.columbia.edu   
United States, Oregon
CODA, Inc Research Department Recruiting
Portland, Oregon, United States, 97214
Contact: Jennifer Wisdom, PhD    971-202-7829    jenwisdom@codainc.org   
United States, South Carolina
Addiction Sciences Division Department of Psychiatry and Behavioral Sciences Medical University of South Carolina Not yet recruiting
Charleston, South Carolina, United States, 29425-8640
Contact: Kevin Gray, MD    843-792-6330    graykm@musc.edu   
United States, Texas
Department of Psychiatry and Behavioral Sciences at UT Health San Antonio. Not yet recruiting
San Antonio, Texas, United States, 78218
Contact: Potter Jennifer, MD    713-504-2244    potterjs@uthscsa.edu   
United States, Utah
Cedar Clinical Research Not yet recruiting
Draper, Utah, United States, 84020
Contact: Paul Thielking, MD    385-501-6116    paul@novamind.ca   
Sponsors and Collaborators
Aelis Farma
National Institute on Drug Abuse (NIDA)
Investigators
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Principal Investigator: Frances Levin, MD Columbia University/NYSPI
Principal Investigator: Jennifer Wisdom, MD CODA, Inc Research Department
Principal Investigator: Kevin Gray, MD Addiction Sciences Division Department of Psychiatry and Behavioral Sciences Medical University of South Carolina
Principal Investigator: Jennifer Potter, MD Department of Psychiatry and Behavioral Sciences at UT Health San Antonio.
Principal Investigator: Larissa Mooney, MD UCLA Department of Psychiatry and Biobehavioral Sciences
Principal Investigator: Rajita Sinha, MD Yale Stress Center - Addiction Program
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Responsible Party: Aelis Farma
ClinicalTrials.gov Identifier: NCT05322941    
Other Study ID Numbers: AEF0117-202
First Posted: April 12, 2022    Key Record Dates
Last Update Posted: June 2, 2022
Last Verified: December 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Aelis Farma:
AEF0117
Cannabis-related Use Disorder
Cannabis subjective effects
Cannabis self-administration cannabis-induced analgesia
Cannabis-related cognitive disorder
Additional relevant MeSH terms:
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Marijuana Abuse
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders