RESIST : Administration of MAP4343 in Antidepressant Non-Responders Patients Experiencing a Major Depressive Episode

NCT03870776 | Completed Phase 2 DMC

• 1 other identifier: MAP4343 / OP103617.MAP
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 10

Brief Summary

The study is a phase II, double-blind, randomized, placebo controlled, parallel, multicentric study in 110 patients with drug resistant depression.

Conditions

Depression

Keywords

Depression; Resistant depression

Outcome Measures

Primary Outcomes (1)

• Hamilton Depression Rating Scale score evolution between baseline and D43

  Assessment of HDRS score with 17 items with sides 0 to 2 or 0 to 4. The scores from 0 to 4 correspond respectively to symptoms: absent, doubtful or insignificant, light, moderate, important, those ranging from 0 to 2 to symptoms: absent, doubtful or slight, overt or severe. The total score consists of the addition of the individual scores.

  43 days

Secondary Outcomes (61)

• Efficacy of treatment assessed by psychopathological evaluations with Hamilton Depression Rating Scale

  43 days

• Efficacy of treatment assessed by psychopathological evaluations with Montgomery and Asberg Depression rating Scale

  43 days

• Efficacy of treatment assessed by psychopathological evaluations with Brief Anxiety Scale

  43 days

• Efficacy of treatment assessed by psychopathological evaluations with Scale of Global Clinical Impressions

  43 days

• Efficacy of treatment assessed by psychopathological evaluations with Quick Inventory of Depressive Symptoms

  43 days

Study Arms (3)

Placebo group A

PLACEBO COMPARATOR

Patients will receive the placebo during 42 days.

Drug: Placebo

MAP4343 group B

EXPERIMENTAL

Patients will receive daily dose 1 during 42 days.

Drug: MAP4343

MAP4343 group C

EXPERIMENTAL

Patients will receive daily dose 2 during 42 days.

Drug: MAP4343

Interventions

MAP4343 DRUG

Daily oral administration of MAP4343

MAP4343 group B; MAP4343 group C

Placebo DRUG

Daily oral administration of Placebo

Placebo group A

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• TRD level from to 2 to 4 inclusive according to the Thase \& Rush classification;
• Patient experiencing a Major Depressive Episode (MDE) according to DSM-5 criteria. MDE can be isolated or recurrent. The diagnosis is based on Mini-International Neuropsychiatric Interview (MINI) test;
• Patient who received a previous antidepressant treatment (AD-Y) in monotherapy with vortioxetine, duloxetine or venlafaxine) at optimized dosages during 6 weeks prior to randomization, associated or not to AD-potentiator (quetiapine), are eligible.
• Hamilton Depression Rating Scale (HDRS) score \> 21;
• Clinical Global Impressions scale (CGI) ≥ 4;
• Male or female patient, aged 18 to 80 years inclusive;
• Females of childbearing potential/Sexually active males with partner of childbearing potential: commitment to consistently and correctly use an acceptable method of birth control (oral, transdermal, systemic or implant contraception birth control, intrauterine devices, diaphragm or condoms) for the duration of the trial and for 4 months after the last study drug administration; Females of non-childbearing potential: either surgically sterilized or at least 1 year postmenopausal (amenorrhea duration at least 12 months);
• Negative pregnancy test at screening baseline;
• Body Mass Index (BMI) between 18 and 32 kg/m2 inclusive;
• Laboratory parameters within the normal range of the laboratory (hematological, blood chemistry tests, urinalysis, hormonology). Individual values out of the normal range can be accepted if judged clinically non relevant by the Investigator;
• Normal ECG recording on a 12-lead ECG at the screening visit:
• \< PR \< 210 ms
• QRS \< 120 ms
• QTcF ≤ 430 ms for male and \< 450 ms for female,
• No sign of any trouble of sinusal automatism,

You may not qualify if:

• MDE with mood congruent or not congruent psychotic characteristics;
• Patient hospitalized following the procedures: Psychiatric care at the request of another person (soins psychiatriques à la demande d'un tiers) or Psychiatric care at the request of the state representative (soins psychiatriques sur décision du représentant de l'Etat);
• Suicidal risk in the last month before randomization (C-SSRS: answer yes to the item 3 and/or answer yes to section suicidal behavior; MINI 5.00; suicidal risk section or item 3 of HDRS ≥ 3);
• History of other psychiatric disorder than DME except global anxiety, social phobia, panic troubles that should be accepted. In particular, patients who experienced a depressive state in bipolar disorder 1 or 2, schizophrenic or schizoaffective disorder should not be included;
• Presence or history of drug hypersensitivity, or certain allergic-prone condition diagnosed that could represent a risk factor for an allergic shock;
• Presence or history of hypersensitivity to vortioxetine, duloxetine, venlafaxine or one of their excipients;
• Any history or presence of severe hepatic insufficiency and/or of hepatic disease which could lead to hepatic insufficiency;
• Patients who are pregnant or breastfeeding. Patients should not be enrolled if they plan to become pregnant during the time of study participation;
• Any drug intake during the last month prior to the first administration except treatments for concomitant pathologies which are stable since at least 3 months; Benzodiazepine-type anxiolytics, hydroxyzine chlorhydrate, and add-on treatments are authorized within limits described in Section 5.3; For the previous drug intake, the investigator should consider the time needed to sufficiently eliminate a drug from body system, e.g. 5 half-lives of the drug;
• Subjects who received MAOI in monotherapy right before the selection (as ttX);
• General anesthesia within 3 months before administration;
• Major surgery within 28 days prior to randomization or major surgery planned during the next 6 months;
• Positive HBs antigen or anti HCV antibody, or positive results for HIV 1 or 2 tests;
• Significant renal disease, defined as a history of chronic renal failure requiring dialysis or kidney transplant, calculated creatinine clearance ≤ 60 mL/min;
• Blood donation (including in the frame of a clinical trial) within 2 months before administration;

Sponsors & Collaborators

• Mapreg: lead
• Eurofins Optimed: collaborator

Study Sites (10)

CHU Angers

Angers, 49900, France

Location

CHU Besançon

Besançon, 25000, France

Location

Cabinet Médical Ambroise Paré

Élancourt, 78990, France

Location

CHD Vendée

La Roche-sur-Yon, 85000, France

Location

Hôpital Fontan 1

Lille, 59000, France

Location

CHU Nantes

Nantes, 44000, France

Location

APHP Hôpital La Pitié Salpétrière - Prinicipal investigator center

Paris, 75013, France

Location

Hôpital Ste Anne

Paris, 75014, France

Location

CHU Henri Laborit

Poitiers, 86000, France

Location

CHRU Tours

Tours, 37000, France

Location

MeSH Terms

Conditions

Depression

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Study Officials

• Isabelle VILLEY, PhD, MBA

  Mapreg

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: There are 3 groups : * Placebo group will receive placebo during 42 days with antidepressant treatment in add-on. * Dose 1 during 42 days with antidepressant treatment in add-on. Upon IDMC recommendation after the first futility analysis (IDMC#5 13-Jun-2022), Dose 1 was stopped from the 17-Jun-2022. * Dose 2 during 42 days with antidepressant treatment in add-on.

Study Record Dates

• First Submitted: February 26, 2019
• First Posted: March 12, 2019
• Study Start: June 1, 2019
• Primary Completion: November 7, 2024
• Study Completion: November 7, 2024
• Last Updated: March 31, 2026

Record last verified: 2026-03

Locations

FR (10)