An Open-label Trial of Add-on Oral Slow-release Ketamine Treatment in Major Depression

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Skane

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

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

Trial duration

13 Mar 2026 → ongoing

Decision date (initial)

2026-03-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Ketabon GmbH · ALF

External identifiers

EU CT number

2025-524841-28-00

ClinicalTrials.gov

NCT07396272

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the preliminary antidepressant efficacy of KET01 after one week of treatment as an adjunctive treatment to complement the initiation of a standard antidepressant agent.

Secondary objectives 7

1. To evaluate the effect of KET01 on depression, anxiety and overall clinical global impression.
2. To evaluate safety and tolerability of KET01.
3. To evaluate if KET01 treatment decreases suicidal ideation.
4. To evaluate if inflammatory markers change during treatment with KET01 and if this is associated with symptom improvement.
5. To evaluate the relationship between KET01 epigenetic markers and resilience.
6. To evaluate KET01-related changes in physical activity and sleep patterns.
7. To investigate participant’s lived experience of changes in mood during KET01 treatment.

Conditions and MedDRA coding

Major Depressive Disorder

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. The subject has given their written consent to participate in the trial.
2. Age ≥ 18 and ≤ 75 years.
3. Body mass index (BMI) ≥ 18 and ≤ 35 kg/m2.
4. Primary diagnosis of MDD meeting Diagnostic and Statistical Manual of Mental Disorders, 5th edition, Text Revision (DSM-5-TR) criteria and one of the following episode characteristics: (1) MDD, single episode, moderate (ICD-10-CM: F32.1); (2) MDD, single episode, severe, without psychotic features (ICD-10-CM: F32.2); (3) MDD, recurrent, moderate (ICD-10-CM: F33.1); (4) MDD, recurrent, severe, without psychotic features (ICD-10-CM: F33.2)
5. Duration of current depressive episode no longer than 12 months prior to screening.
6. MADRS score ≥ 22 at screening
7. Willingness to start a new, conventional antidepressant treatment which is chosen by the treating physician with regards to side effect profile and previous treatments, together with KET01, dosed according to the prescribed schedule.
8. Willingness to terminate any ongoing antidepressant treatment if deemed ineffective by study physician in accordance with clinical practice (tapering or immediate stop), followed by a wash-out phase of at least 7 days without medication before treatment with the new antidepressant is initiated together with KET01.
9. For women of childbearing potential (WOCBP; definition: A WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilisation (hysterectomy or bilateral oophorectomy) or is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over age 45 in the absence of other biological or physiological causes.): Must be willing to undergo pregnancy tests and will be required to use highly effective contraceptive measures from the time of informed consent until 28 days after last IMP intake. Methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods. Such methods include combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral or injectable); implantable intrauterine device (IUD); intrauterine hormone-releasing system (IUS), bilateral tubal occlusion or practicing sexual abstinence (if this is in line with the preferred and usual lifestyle of the participant).
10. For male participants with a partner of childbearing potential (see definition of WOCBP above): Must be willing to use adequate contraceptive measures (barrier method) or practice sexual abstinence (if this is in line with the preferred and usual lifestyle of the participant) from the time of informed consent until 28 days after last IMP intake. Note: These requirements also apply for male participants who have had a vasectomy.

Exclusion criteria 26

1. Known hypersensitivity or intolerance to ketamine or any of the excipients.
2. Pregnancy, breastfeeding or planned pregnancy (if female).
3. High suicide risk according to the overall assessment of the research physician.
4. Known psychiatric and neurological concomitant condition of: MDD, single episode, severe, with psychotic features (ICD-10-CM: F32.3). MDD, recurrent, severe, with psychotic features (ICD-10-CM: F33.3) Schizophrenia spectrum and other psychotic disorders (ICD-10-CM: F21, F22, F23, F20.81, F20.9, F25.0, F25.1, F06.0, F06.1, F06.2, F28 and F29) or bipolar disorder (ICD-10-CM: F31), other mental disorder due to known physiological condition (ICD-10-CM: F06). Participants with first-degree relatives (parents, brothers, sisters or children) with psychotic or bipolar disorders are also not considered eligible. Paranoid or schizoid personality disorder (ICD-10-CM: F60.0, F60.1). Antisocial, borderline, histrionic or narcissistic personality disorder (ICD 10 CM: F60.2, F60.3, F60.4, F60.81). Neurodevelopmental disorders, e.g. moderate to profound intellectual developmental disorders (ICD-10-CM: F71, F72, F73), or autism spectrum disorders (ICD-10-CM: F84).
5. Known or suspected lifetime history of surgical procedures involving the brain or meninges, encephalitis, meningitis, degenerative central nervous system (CNS) disorder, epilepsy (excluding uncomplicated childhood febrile seizures with no sequelae) or any other disease/procedure/accident/intervention which, according to the investigator is deemed associated with significant injury to or malfunction of the CNS.
6. History of significant head trauma within the past 2 years prior to Visit 1.
7. History of cerebrovascular event (e.g. stroke, prolonged ischaemic neurologic deficit [PRIND], transient ischaemic attack).
8. Known or suspected ongoing cardiac disease (e.g. unstable angina, congestive heart failure, tachyarrhythmia or myocardial infarction).
9. Clinically significant abnormal electrocardiogram findings at Visit 1 which may jeopardize participant’s safety according to the investigator.
10. Untreated or uncontrolled hypertension (after 5 minutes of rest, systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 120 mmHg confirmed by three sequential measurements with at least 5 minutes between the single measurements).
11. Laboratory findings suggesting impaired hepatic function or liver cirrhosis i.e. gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) values > 2x times the upper limit of normal (ULN) or total bilirubin > 1.5 times the ULN at Visit 1. Participants with an isolated increase of indirect bilirubin not previously documented as a diagnosis of Gilbert’s syndrome must be discussed with the medical monitor.
12. Known hepatitis B or C.
13. Estimated Glomerular Filtration Rate (eGFR) < 60 mL/min/1.73 m2 or creatinine > 200 µmol/L at Visit 1 or ongoing dialysis or kidney transplants.
14. Diabetes mellitus with a haemoglobin A1c (HbA1c) value > 64 mmol/mol at the screening visit.
15. Hyperthyroidism.
16. Uncontrolled hypothyroidism i.e. not at stable treatment with thyroid hormones (triiodothyronine/thyroxine [T3/T4]) within the 6 weeks before Visit 1 or abnormal thyroid stimulating hormone (TSH) and free thyroxine (fT4) values at Visit 1.
17. History (within 5 years before Visit 1) of complicated cystitis (defined as cystitis in males; due to anatomical abnormalities; due to immunocompromised state, in pregnant women; recurrent infections despite adequate treatment; infections occurring after instrumentation such as nephrostomy).
18. Any other significant disease or disorder which, in the opinion of the investigator, may either put the participant at risk because of participation in the trial, or jeopardise the conduct of the trial according to the protocol.
19. Previous administration of ketamine (with exception of known or suspected ketamine-anaesthesia) or esketamine.
20. Prohibited prior and concomitant therapies and medication (see 7.3 Concomitant use of other medicinal products and treatments in Study Protocol).
21. History of moderate to severe alcohol use disorder or substance use disorder, including e.g. benzodiazepines, opiates, ketamine, hallucinogens and related drugs, stimulants (e.g. phencyclidine [PCP]), lysergic acid diethylamide [LSD], 3,4 methylenedioxymethamphetamine [MDMA], dextromethorphan, amphetamines, cocaine) or cannabis, except nicotine and caffeine, within 6 months before Visit 1 or a positive drug abuse test except for allowed medication prescribed for a medical condition.
22. Participation in other treatment studies.
23. Ongoing electroconvulsive treatment (ECT) or repetitive transcranial magnetic stimulation (rTMS).
24. Ongoing compulsory psychiatric care.
25. Other reason, as assessed by the investigator, that prevents the research subject’s participation such as risk that the subject is unable to complete the trial (non-compliance).
26. Recently started psychotherapy (within 6 weeks) or planning to start such treatment during participation in the trial.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in total Montgomery-Åsberg Depression Rating Scale (MADRS) score after one week of treatment (day 8) compared to the baseline visit (day 1).

Secondary endpoints 15

1. Change in total MADRS score between baseline (day 1) and day 3, 5, 15 and 29.
2. Change in Clinical Global Impression – Severity (CGI-S) rating scale from baseline (day 1) to every post-baseline measurement (day 3, 5, 8, 15, 29)
3. Total score of Clinical Global Impression – Efficacy Index (CGI-E) rating scale at every post-baseline measurement (day 3, 5, 8, 15, 29)
4. Change in Patient Health Questionnaire-9 (PHQ-9) between baseline (day 1) and the two follow-up visits (day 15 and 29)
5. Change in composite inflammatory depressive symptom score (InfDep score) consisting of PHQ-9 items # 3, 4 and 5 between baseline (day 1) and the two follow-up visits (day 15 and 29)
6. Change in generalized anxiety disorder-7 (GAD-7) between baseline (day 1) and the two follow-up visits (day 15 and 29)
7. Change in Columbia Suicide Severity Rating Scale (C-SSRS) between baseline (day 1) and three post-baseline visits (day 8, 15, 29)
8. Response rate (≥ 50% decrease from baseline in MADRS total score) at every post-baseline visit (day 3, 5, 8, 15, 29).
9. Remission rate (MADRS score of ≤10) at every post-baseline visit (day 3, 5, 8, 15, 29).
10. Change in Sedentary Behaviour (SED), Low-Intensity Physical Activity (LPA) and Moderate- to Vigorous Physical Activity (MVPA) and number of steps, between baseline (day 1) and every post-baseline visit (day 3, 5, 8, 15, 29).
11. Change in sleep patterns total sleep time (TST), sleep efficiency (SE), wake after sleep onset (WASO) and number of awakenings (NA) between baseline (day 1) and every post-baseline visit (day 3, 5, 8, 15, 29).
12. Changes in blood plasma levels of the inflammatory biomarkers high-sensitive C-reactive protein, interleukin-6, tumor necrosis factor alpha and white blood cell count between baseline (day 1) and three post-baseline visits (day 8, 15, 29).
13. Change in DNA methylation patterns between baseline (day 1) and two post-baseline visits (day 8 and day 29).
14. Change in Connor-Davidsson Resilience Scale (CD-RISC-25) between baseline (day 1) and two post-baseline visits (day 8 and 29).
15. Patient's personal experience with effect of ketamine treatment on mood (qualitative interview with open-ended question at last follow-up (day 29)).

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Skane

Sponsor organisation

Region Skane

Address

Dockplatsen 26, Malmo S:t Petri Malmo S:t Petri

City

Malmo

Postcode

211 74

Country

Sweden

Scientific contact point

Organisation

Region Skane

Contact name

Mirjam Wolfschlag

Public contact point

Organisation

Region Skane

Contact name

Mirjam Wolfschlag

Locations

1 EU/EEA country · 1 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 14 files

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

Application history

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