Low Dose IL-2 Therapy in Patients With a Depressive Episode in the Course of a Bipolar Disorder (DEPIL-2)

• ClinicalTrials.gov Identifier: NCT04133233
• Recruitment Status: Recruiting
• First Posted: October 21, 2019
• Last Update Posted: November 7, 2022
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborator: Iltoo Pharma
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Study Description

Brief Summary:

The purpose of this study will be to demonstrate improvement of the T regulatory cells (Treg) response, under add on low-dose Interleukin 2 (ld-IL2) in patients with bipolar disorders experiencing a depressive relapse

Condition or disease	Intervention/treatment	Phase
Bipolar Depression	Drug: ILT101; Drug: Placebos	Phase 2

Detailed Description:

A hypothesis still under study concerning the pathophysiological mechanisms of bipolar disorder concerns an immunological disorder that could possibly be involved in this disease and during a depressive episode. In particular, that the multiplication of a certain category of white blood cells called "regulators" that block the toxic effect of more aggressive white blood cells could improve these disorders.

The aim of this research is therefore to check the effectiveness and safety of injections of Interleukin 2 (IL-2) to induce this multiplication of regulatory white blood cells.

IL-2 is a natural protein released by white blood cells that is used for the proper functioning of the immune defence system. The favourable effects of injecting small doses of IL-2 are known and assessed in other diseases, including autoimmune diseases.

The secondary objective of this study is to assess the effect of these injections on patient's mood, which could be improved by this treatment.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized, double-blind, placebo-controlled (2 active: 1 placebo), multicentre, 6-week, proof-of concept trial of add on low dose IL-2 therapy in patients with a depressive episode in the course of a bipolar disorder, hospitalized or not. The study will be an add-on study, with no wash-out period.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Low Dose IL-2 Therapy in Patients With a Depressive Episode in the Course of a Bipolar Disorder
• Actual Study Start Date: June 15, 2020
• Estimated Primary Completion Date: February 15, 2023
• Estimated Study Completion Date: April 15, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: active treatment; IL-2 (ILT-101) Sub-cutaneous 1 million UI/j	Drug: ILT101; Treatment administration consists in a first course of five-day treatment (induction), followed by a single injection every week for 4 weeks (maintenance; from Week 3 to Week 6); Other Name: IL2
Placebo Comparator: placebo; placebo Sub-cutaneous The Placebo used is a sterile powder that will be produced by the CMO (AMATSI, France).	Drug: Placebos; Treatment administration consists in a first course of five-day treatment (induction), followed by a single injection every week for 4 weeks (maintenance; from Week 3 to Week 6); Other Name: placebo

Outcome Measures

Primary Outcome Measures :

1. change of Treg response [ Time Frame: baseline to Day 5 ]
   Percentage Treg fold increase compared to baseline at Day 5

Secondary Outcome Measures :

1. Treg response, under ld-IL2 in relation with symptomatic assessment of mood improvements [ Time Frame: from baseline to week 6 ]
   Change in the value of Montgomery Asberg Depression Rating and in The inventory of depressive symptomatology
2. changes in immune homeostasis under ld-IL2 in relation with symptomatic assessment of mood improvements [ Time Frame: between Day 5 and Day 60 ]
   variation in Treg /CD4+ at different visit expressed as percentage of baseline value
3. Assess the incidence of ld-IL2(safety and tolerability) in patients with a depressive episode in the course of a bipolar disorder [ Time Frame: baseline to Day 60 ]
   Frequency and type of adverse events during the trial.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• A depressive episode according to DSM-V criteria in the course of a bipolar disorder
• MADRS score > 17
• Already on a mood stabilizer and/or antidepressant
• Patient with a normal or controlled thyroid function
• Male or female both using effective methods of contraception during treatment if sexually active.

Exclusion Criteria:

• - Contraindication to IL-101 therapy:
• Hypersensitivity to active substance or excipient;
• Active infection requiring antibiotics therapy;
• Organ failure (e.g., liver, kidney, lung and heart);
• Immunosuppressed patient
• Hepatotoxic, nephrotoxic, myelotoxic or cardiotoxic drugs
• Other chronic diseases
• Signs of active infection requiring treatment
• Previous history of organ transplantation
• Leukocytes < 4000 / mm3, platelets < 100 000 / mm3, Hemoglobin < 10.0 g/dL or 6.2 mmol/L, red cell blood < 3.5 T/L.
• Anti-TPO or anti-TG or anti-TRACKS positive at inclusion.
• Use of anti-inflammatory medication on a regular basis for a chronic inflammatory/autoimmune Disorder (NSAD, immunosuppressant IV-Ig based treatment);
• Ongoing fever < 38
• uncontrolled diabetes type I or II;
• Existing cancer or history of cancer in the last 5 years (except skin epidermoid cancer or in-situ cervix cancer);
• Existing or planned pregnancy or lactation;
• Person under legal protection (1121-8 of CSP, Public Health Code
• Pregnant and parturient and Breast feeding women (1121-5 of CSP)
• legally detained person (1121-6 of CSP)
• hospitalisation without consent
• under the age of majority (1121-7of CSP)
• Immediate risk for suicidal behaviour (MADRS-item 10 >2 or columbia > 2 for suicide idea);
• Known HIV infection or clinically manifest Acquired Immune Deficiency Syndrome (AIDS), Parkinson's or Alzheimer's disease, or any other serious condition likely to interfere with the conduct of the trial;
• Participation to an interventional study concomitantly or within 30 days prior to this study, except in the cohorts studies aiming at the analysis of immuno-inflammatory biomarkers and/or brain imaging studies.
• Patients thought to be unreliable or incapable of complying with the requirements of the protocol;
• Patient is relative of, or staff directly reporting to the investigator;
• Patient is employee of the sponsor.

Contacts and Locations

Contacts

Contact: Marion Leboyer, Pr; 01 49 81 30 51 ext +33; marion.leboyer@inserm.fr

Contact: Jean-Romain Richard; 01 49 81 31 31; jean-romain.richard@inserm.fr

Locations

France

Pr Marion Leboyer; Recruiting

Créteil, Hôpital Albert Chenevier, France, 94010

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Iltoo Pharma

Investigators

• Study Chair: Marion Leboyer, Pr; Assistance Publique - Hôpitaux de Paris

More Information

• Responsible Party: Assistance Publique - Hôpitaux de Paris
• ClinicalTrials.gov Identifier: NCT04133233
• Other Study ID Numbers: D20180617; 2018-002777-22 ( EudraCT Number ); MEDAECNAT-2018-10-00069 ( Other Identifier: ANSM )
• First Posted: October 21, 2019
• Last Update Posted: November 7, 2022
• Last Verified: November 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Assistance Publique - Hôpitaux de Paris:

Low dose of IL-2; Treg response

Additional relevant MeSH terms:

Bipolar Disorder; Bipolar and Related Disorders; Mood Disorders; Mental Disorders