CAPSI - Cancer related major depression treated with a single dose of psilocybin - a multicenter randomized placebo controlled double blind clinical trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Stockholm – SLSO

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

15 May 2024 → ongoing

Decision date (initial)

2023-11-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

The Swedish Research Council

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The primary objective of this study is to evaluate the efficacy of a single 25 mg oral dose of
psilocybin for major depressive disorder (MDD) compared to an active placebo (psilocybin 1
mg) assessed as the difference between groups in changes in depressive symptoms, in the
following PICO Population: 20-80 (inclusive) years old, current depressive episode (PHQ-922
≥10), >1 month after cancer diagnosis, with at least 12 months of life expectancy, willingness
to abstain from other psychotherapeutic or antidepressant treatments during the study (wash
out time 5 half-lives).

Conditions and MedDRA coding

Malignant tumours ICD 10 C00 to C97

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. signed informed consent via minavårdkontakter.se 2. Are 20 to 80 (inclusive) years old at the time of signed informed consent 3. Are able to read, speak, and understand Swedish 4. Are able and willing to adhere to study requirements, including attending all study visits, preparatory and follow-up sessions, and completing all study evaluations 5. Are able to swallow capsules 6. Women of childbearing potential (WOCBP) must agree to practice an effective means of birth control throughout the duration of exposure to the Investigational Product, from Screening through the Day 8. 7. A diagnosis of a malignant neoplasm with a diagnostic code from C00 to C97 according to the International Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) 8. ≥1 month after cancer diagnosis and ≥ 12 months of life expectancy at time of inclusion 9. physical functioning performance status 0-2 (WHO/ECOG) 10. Meet ICD-10 criteria for a diagnosis of major depressive disorder and are currently experiencing a major depressive episode of a. at least a 30-day duration at the time of the Screening b. less than 1 year at time of Screening 11. Have moderate-severe depression symptoms at Screening, as defined by a Screening PHQ-9 total score ≥ 10. 12. Are willing to abstain from other psychotherapeutic or antidepressant treatments during the study period (180 days; wash out time 5 half-lives). Note, if antidepressant treatment becomes needed as determined by the study physician this will be supported by the study personnel. 13. Have an identified support person. 14. Agree to be driven/accompanied home (or to an otherwise safe destination) by the support person, or another responsible party, following dosing 49

Exclusion criteria 1

1. 1. Last contact with health care due to cancer monitoring or treatment >1 year ago. 2. Women who are pregnant, as indicated by a positive urine pregnancy test at Screening or Baseline. Women who intend to become pregnant during the study or who are currently nursing. 3. Unwilling or unable to discontinue formal psychotherapy 4. Ongoing antidepressant drug treatment. No interruption of ongoing antidepressant treatment will be done on the initiation of the study personnel. Patients will be encouraged to discuss any interruption with their responsible clinical physician. 5. Have previously during the current episode received the following non-medication treatments: a. deep brain stimulation (DBS) b. vagus nerve stimulation (VNS) 6. Currently receiving electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) 7. Unable or unwilling to discontinue any current medications that are known uridine diphosphate (UDP) or glucuronosyltransferase (UGT) enzyme modulators (eg valproate) Note: Any prohibited agents must have been stopped at least 5x the elimination half-life of the specific drug plus one week at the time of Baseline. See Appendix A for a full list of prohibited medications. 8. Report psychedelic substances use ever o Note: Psychedelic substances include psilocybin, Lysergic acid diethylamide (LSD), mescaline (and natural products containing mescaline including peyote and San Pedro cactus), N,N-Dimethyltryptamine (DMT), natural products containing DMT including ayahuasca and 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT), ibogaine, 2C compounds, 3,4-methylenedioxy- methamphetamine (MDMA), methylone or other psychedelics. 9. Cancer at time of inclusion involving the CNS (as determined by a clinical examination or MRI) 10. Cancer treatment/follow up regime determined to be incompatible with the CAPSI protocol (eg due to time lines, interaction between cancer treatment and psilocybin 25 mg or 1 mg exposure). 11. Have any of the following cardiovascular conditions: a. congenital long QT syndrome (prior diagnosis), b. any of the following if disabling physical exercise similar to walking two stairs without pause: coronary artery disease, cardiac hypertrophy, cardiac ischemia, congestive heart failure, c. a clinically significant Screening ECG abnormality (e.g., atrial fibrillation); oNote: A QTcF interval > 450 milliseconds is considered a clinically significant ECG abnormality d. artificial heart valve; or 50 CAPSI protocol version no 1 date 230712 e. any other significant current or history of cardiovascular condition, based on the clinical judgment of study physician, that would make a participant unsuitable for the study 12. At Screening or Baseline have elevated blood pressure as defined as: a. Screening blood pressure SBP >150 mmHg or DBP > 95 mmHg on three separate readings; or b. Baseline blood pressure SBP >160 mmHg or DBP > 100 mmHg on three separate readings 13. Have a history of stroke or Transient Ischemic Attack (TIA) 14. Have moderate to severe hepatic impairment, as indexed by a Child-Pugh score ≥ 7 15. Have uncontrolled epilepsy 16. Have insulin-dependent diabetes o Note: Participants who are taking oral hypoglycemic agent and have a history of hypoglycemia requiring medical intervention will be excluded 17. Are unable or unwilling to adhere to the following medication requirements: a. Agree to suspend sildenafil (Viagra®), tadalafil, or similar medications at least 72 hours prior to dosing 18. Have a positive urine drug test including Amphetamines, Barbiturates, Buprenorphine, Benzodiazepines, Cocaine, Cannabis, Methamphetamine, MDMA, Methadone, Opiates (Morphine, Oxycodone), Phencyclidine (PCP), and Tetrahydrocannabinol (THC). Exceptions are made for prescribed Benzodiazepines (stable dose for sleep or anxiety).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint for the acute-phase (Day 0 to Day 42) is the endpoint score on the observer-rated MADRS total score. This will be assessed using ANCOVA. The primary endpoint for the follow-up phase (Day 43 to Day 180) is days to initiation of antidepressant treatment (antidepressants or psychotherapy) or hospitalization for depression from Day 43 to the date when either of the events has occurred.

Secondary endpoints 1

1. MADRS at day 8 (ANCOVA x1) MADRS-S at all evaluations between Day 0 and Day 42 (MMRM x1) SDS, GAD-7 and HADS at Day 42 (ANCOVA x3) CGI, EQ-5D-5L at Day 8 and Day 42 (ANCOVA x6) AQOL-6D at Day 42 (ANCOVA x1). MADRS at Day 90 and Day 180 (ANCOVA x2) MADRS-S at all evaluations between Day 43 and Day 180 (MMRM x1) SDS, GAD-7, HADS at Day 180 (ANCOVA x3) CGI, EQ-5D-5L at Day 90 and Day 180 (ANCOVA x6) AQOL-6D at Day 90 and Day 180 (ANCOVA x2)

Investigational products

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

Test 1

Comparator 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Stockholm – SLSO

Sponsor organisation

Region Stockholm – SLSO

Address

Solnavagen 1 E, S:t Matteus S:t Matteus

City

Stockholm

Postcode

113 65

Country

Sweden

Scientific contact point

Organisation

Region Stockholm – SLSO

Contact name

Johan Lundberg

Public contact point

Organisation

Region Stockholm – SLSO

Contact name

Opokua Britton Cavaco

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

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

Documents 30 files

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

Application history

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