Regression of Atherosclerosis induced by liFe chAnging Experience with psiLocybin

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Psyon s.r.o.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

14 Oct 2024 → ongoing

Decision date (initial)

2024-11-21

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Psyon, s.r.o.

External identifiers

EU CT number

2024-517902-27-00

EudraCT number

2022-003381-21

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

To demonstrate regression of atherosclerotic plaque volume between baseline (F2) and follow-up invasive coronary artery examination (F7) performed 365 days +- 28 days after administration (F4) in patients with ischemic heart disease treated with standard hypolipidemic therapy (add-on therapy) and randomized to psilocybin- or midazolam-assisted psychotherapy as a negative control.

Secondary objectives 4

1. Change in the composition of atherosclerotic plaques between the baseline (F2) and follow-up invasive coronary artery examination (F7) performed 365 days +- 28 days after IMP administration (F4).
2. Reduction in the incidence of the highest-risk phenotype of atherosclerotic plaque - thin-cap fibroatheroma (TCFA), between baseline (F2) and follow-up invasive coronary artery examination (F7) performed 365 days +- 28 days after IMP administration (F4).
3. Measurement of the increase in fibrous cap thickness using optical coherence tomography between baseline (F2) and follow-up invasive coronary artery examination (F7) performed 365 days +- 28 days after IMP administration (F4).
4. Safety assessment (blood pressure, heart rate) of study medication.

Conditions and MedDRA coding

Stable Ischemic Heart Disease

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Men and women aged 18-80.
2. Diagnosis of stable ischemic heart disease (I25.9).
3. A coronary finding of stenosis on one of the major coronary arteries of at least 2.5 mm in diameter with narrowing that does not exceed 50 % of the reference diameter and is on the native artery without previous intervention.
4. Patient's cognitive ability to fully understand CT information and study questionnaires.
5. Participants of childbearing age or with preserved fertility must agree to use prescribed contraceptive methods throughout the clinical trial..The following methods of contraception are required: (a) Women - we require at least one of the highly effective conception protection methods listed below: Combined (estrogen and progesterone) hormonal contraceptives (oral, transdermal, or intravaginal); Progesterone hormonal contraceptives (oral, transdermal, or intravaginal); Intrauterine device (IUD); Intrauterine Hormone Releasing System (IUS); Bilateral fallopian tube closure; Bilateral interruption of fallopian tubes in a partner; Sexual abstinence. (b) Men - use of at least an adequate barrier contraceptive method (condom) or sexual abstinence from the signing of the informed consent until 48 hours after administration of the study medication (study visit F4).

Exclusion criteria 30

1. Severe neurological disease of the CNS. In case of suspicion of such disease, the CNS imaging (CT/MR) must be negative.
2. Any other serious psychiatric illness based on psychiatric examination
3. Stable treatment with antidepressants / thymostabilisers / antipsychotics in a non-hypnotic indication (doses must not achieve the antidepressant, antipsychotic or thymostabilising effect as per SPC).
4. Renal insufficiency with creatinine clearance < 0.6 ml/s
5. Presence of suicidal ideation or suicidal behavior based on the C-SSRS version Lifetime/Recent (L/R) or C-SSRS version since last visit (SLV), specifically, a "yes" response to question 4 and 5 in the past 6 months and/or any "yes" response to suicidal behavior questions in the past 6 months and/or clinical examination
6. Current or history of alcohol or drug dependence F1X.X. unless at least 2 years of abstinence can be demonstrated
7. Other inappropriateness of the patient's classification based on the clinical judgment of the examining physician
8. Known intolerance or allergy to psilocybin or midazolam
9. Pregnancy or breastfeeding
10. Hepatic dysfunction with GGT, AST, ALT values > 5 times the upper limit of normal, total bilirubin > 50 μmol/l
11. Cardiovascular instability in the sense of uncorrected hypertension (baseline BP ≥ 140/95 mm Hg - mean of 3 measurements), manifest heart failure NYHA II or more, left ventricular ejection fraction < 50%, history of ventricular tachycardia except reperfusion arrhythmias, atrial fibrillation with resting ventricular rate > 100 beats/min (mean of 3 measurements)
12. Severe thrombocytopenia < 50 x 10^9/l, resistant to replacement
13. Anatomical findings not allowing IVUS and OCT examination. i.e. tortuous coronary artery, markedly calcified stenosis.
14. Myasthenia gravis
15. Epilepsy including a history of isolated epileptic seizures
16. Known paraneoplastic syndrome or ectopic hormone production by the primary tumour, which could include hypercalcemia, Cushing's syndrome, hypoglycaemia, SIADH, or carcinoid syndrome.
17. Sleep apnoea syndrome
18. Status post aortocoronary bypass with a functional graft to the artery of interest
19. Diabetes mellitus on insulin or corrected with oral antidiabetic agents if there is a history of clinically significant hypoglycaemia.
20. Prior myocardial infarction less than 6 weeks ago with full revascularization
21. Prior stroke and/or TIA less than 6 months ago
22. Clinically significant peripheral vascular disease (acute venous thrombosis, chronic venous insufficiency at the stage of tibial ulceration, lower extremity ischemic disease at the stage of defects)
23. Focal neurological findings
24. Pulmonary disease with a reduction in vital capacity to lower than 75% of appropriate values, or FEV1 < 1,5 l
25. Psychoterapy initiated less than 3 months prior to the start of the RAFAEL study
26. Patient's condition does not allow compliance with concomitant therapy
27. Inability to orally administer study medication in capsule form
28. Untreated or incompletely compensated hyperthyroidism
29. Use of psilocybin or another serotonergic psychedelic in the past 12 months
30. Any current or history of psychotic illness from the diagnosis F2X.X

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in the atherosclerotic plaque volume between the baseline (F2) and follow-up invasive coronary artery examination (F7) performed 365 days ± 28 days after IMP administration (F4) measured with intravascular ultrasound (IVUS).

Secondary endpoints 4

1. Change in the composition of atherosclerotic plaques between the baseline (F2) and follow-up invasive coronary artery examination (F7) 365 days ± 28 days after IMP administration (F4)
2. Reduction in the incidence of the thin-cap fibroatheroma (TCFA), between the baseline (F2) and follow-up invasive coronary artery examination (F7) performed 365 days ± 28 days after IMP administration (F4)
3. Change in the increase of the in fibrous cap thickness measured with optical coherence tomography between the baseline (F2) and follow-up invasive coronary artery examination (F7) 365 days ± 28 days after IMP administration (F4)
4. Safety evaluation (blood pressure, heart rate) of study medication

Investigational products

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

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Psyon s.r.o.

Sponsor organisation

Psyon s.r.o.

Address

Cistovicka 249/11, Repy Repy

City

Prague

Postcode

163 00

Country

Czechia

Scientific contact point

Organisation

Psyon s.r.o.

Contact name

Principal Investigator

Public contact point

Organisation

Psyon s.r.o.

Contact name

Principal Investigator

Third parties 1

Locations

1 EU/EEA country · 2 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 25 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