Efficacy and Safety of REL-1017 for Major Depressive Disorder

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Mggm LLC

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

4 Dec 2024 → 1 Feb 2025

Decision date (initial)

2024-05-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

MGGM LLC

External identifiers

EU CT number

2023-507399-27-00

WHO UTN

U1111-1300-5155

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety

To evaluate the therapeutic efficacy of REL-1017 compared to placebo in participants with inadequate response to ongoing ADT at Day 28 on the Montgomery-Åsberg Depression Rating Scale (MADRS10) total score

Secondary objectives 9

1. To evaluate the therapeutic efficacy of REL-1017 compared to placebo in participants with inadequate response to ongoing ADT in the following measurements: • Decrease from Baseline to Day 7 of the MADRS10 total score
2. MADRS10 response rate (improvement ≥50% compared with total Baseline score) at Day 28
3. MADRS10 remission rate (total score ≤10) at Day 28
4. Decrease from Baseline to Day 28 of the CGI-S score
5. To evaluate safety and tolerability of REL-1017
6. To evaluate the effect of REL-1017 on electrocardiographic parameters
7. To evaluate the impact of REL-1017 for 28 days compared to placebo in subjects with inadequate response to ongoing ADT on measures of depression, anxiety, sleep, sexual function, cognitive function, select biomarkers, and quality of life
8. To evaluate the effect of REL-1017 on potential blood markers of MDD or treatment outcome
9. To evaluate the PK of REL-1017

Conditions and MedDRA coding

Major Depression

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Written informed consent.
2. Male or female participant, aged 18 to 65 years, inclusive.
3. Body mass index (BMI) between 18.5 and 30.0 kg/m2, at Screening
4. Participant understands the study requirements, is willing and able to commit to meet all study requirements, adhere to both approved ADT and study drug regimen, and complete all assessments and all scheduled visits, per Investigator judgment
5. Women of childbearing potential (WOCBP) and men whose sexual partners are WOCBP must use at least 1 highly effective method of contraception from Screening and for at least 2 months after the last study drug administration
6. Diagnosed with MDD as defined by the Diagnostic and Statistical Manual, Fifth Edition (DSM-5), and confirmed by the SCID-5 CV.
7. Diagnosed with a current MDE lasting from 8 weeks to 24 months as defined by the DSM-5 and confirmed by the SCID-5 CV, as well as confirmation of MADRS10 and PHQ9 scores of moderate to severe MDD and contextual appropriateness to be a participant in this study by the Investigator.
8. Diagnosed with a current MDE lasting from 8 weeks to 24 months as defined by the DSM-5 and confirmed by the SCID-5 MDD, as well as confirmation of MADRS10 score, ATRQ, and contextual appropriateness to be a participant in this study by the Investigator
9. Treated for at least 6 weeks prior to Screening, stabilized for at least 6 weeks prior to Baseline, and experiencing approximately 10% to 50% improvement, as assessed by the clinician, and documented on the ATRQ, from an approved dosing regimen of ADT (eg, SSRI, SNRI, bupropion [a NDRI and nicotinic receptor antagonist] or atypical antipsychotic adjunctive antidepressant, alone or in combination) during the current MDE, and committed to remaining on the same stable dosing regimen for the Screening period and for the entire study, at or above the minimally adequate dose listed in the ATRQ. Subjects with clinician assessed antidepressant tolerance/tachyphylaxis are eligible even if the current ADT response is <10%.
10. As ascertained by an independent adjudicator, the data transcribed in the eCRF from the ATRQ, SCID-5-CV, PHQ9, MADRS, C-SSRS, HAM-A are complete, consistent and compatible with the primary diagnosis of moderate to severe MDD with inadequate response to an adequate trial of antidepressants as defined in the criterion above. • A cut-off of ≥ 26 on MADRS is defined for study entry. The remaining scales will be checked by the independent adjudicator only for ensuring consistency of diagnosis for inclusion of patients, i.e. diagnosis of MDD as defined by the DSM-5.
11. Baseline (Day 1) MADRS10 score not exceeding >30% and <20% compared to the Screening MADRS

Exclusion criteria 7

1. History or presence of clinically significant abnormality as assessed by physical examination, medical history, 12-lead ECG, vital signs, or laboratory values, which in the opinion of the Investigator would jeopardize the safety of the participant or the validity of the study results.
2. Any medical, psychiatric condition, or social context that, in the opinion of the investigator, is likely to unfavourably alter the risk-benefit of participant, to interfere with protocol compliance, or to confound safety or efficacy assessments
3. Triplicate 12-lead ECG with average QTcF ≥450 msec, and/or a QRS interval ≥120 msec at Screening
4. Poorly controlled diabetes as defined by a glycosylated hemoglobin (HbA1c) >8.5% (69 mmol/mol), despite standard care. (Note: re-screening of patients who has failed the screening process due to not meeting this exclusion criterion is allowed after diabetes treatment adjustment and level of glycosylated hemoglobin (HbA1c) back to <8.5%)
5. Any long-term use (ie, >120 days in a 6-month period) of prescribed opioids or controlled substances within 6 months, prior to Screening – as verified by appropriate medical records.
6. More than 3 doses of opioids use within 30 days prior to Baseline
7. Pro Re Nata (PRN) use of any anxiolytic, antipsychotic, anticonvulsant/antiepileptic, mood stabilizer, or stimulant medications or supplements within 30 days prior to Screening. Note: Participants should be medically stable; when discontinuation of a prohibited medication is indicated, the prohibited medication should be appropriately tapered to avoid withdrawal symptoms. Benzodiazepines, atypical antipsychotic drugs, anticonvulsants/antiepileptic drugs, mood stabilizers, stimulants, and supplements, including St. John’s Wort, [Hypericum Perforatum), taken regularly and daily at a stable dose for at least six weeks prior to Screening, for the treatment of MDD or its symptoms, are permitted.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Decrease from Baseline to Day 28 of the MADRS10 total score in REL-1017 compared to placebo in participants with inadequate response to ongoing ADT

Secondary endpoints 17

1. Decrease from Baseline to Day 7 of the MADRS10 total score
2. MADRS10 response rate (improvement ≥50% compared with total Baseline score) at Day 28
3. MADRS10 remission rate (total score ≤10) at Day 28
4. Decrease from Baseline to Day 28 of the CGI-S score
5. Effect of the following covariates on primary endpoint: MADRS10 total score as a function of severity at baseline (MADRS baseline >35) tachyphylaxis/tolerance (yes/no), TRD (yes/no), time since first diagnosis of MDD, sex and age.
6. CGI-I score at Day 7 and Day 28
7. Decrease from Baseline to Day 28 in MADRS10 component scores
8. Change from Baseline in DSST
9. Change from Baseline in ASEX
10. Change from Baseline to Day 28 of each Sheehan Disability Scale (SDS) domain score
11. Change from Screening to Day 28 of the Hamilton Anxiety Depression Scale (HAM-A) total score
12. Change from Baseline to Day 28 of potential blood markers of MDD or treatment outcome
13. Treatment-emergent adverse events (TEAEs)
14. • Vital signs and weight • Physical examination • Clinical laboratory parameters (chemistry, hematology, and urinalysis)
15. C-SSRS (Columbia Suicide Severity Rating Scale) Change from baseline at each assessment point. Safety end point and used to identify behaviors that may be indicative of an individual's intent to commit suicide and to guide adoption of appropriate measures
16. Evaluate the effects on QT interval with Fridericia's correction (QTcF) at Day 28
17. PK evaluation at Day 28

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Mggm LLC

Sponsor organisation

Mggm LLC

Address

85 Baker Road

City

Kerhonkson

Postcode

12446-1701

Country

United States

Scientific contact point

Organisation

Mggm LLC

Contact name

Paolo Manfredi

Public contact point

Organisation

Mggm LLC

Contact name

Paolo Manfredi

Third parties 1

Locations

1 EU/EEA country · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 31 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications