A Phase 2b double-blind, randomized, low-dose comparator-controlled clinical trial to assess the efficacy and safety of PEX010 in psilocybin-assisted psychotherapy for the treatment of adjustment disorder due to incurable cancer diagnosis

This Phase 2b study is a double-blind, 1:1:1 randomized, study to assess the efficacy, safety and tolerability of 25 mg, 10 mg and 1 mg [low-dose comparator] PEX010 in participants with adjustment disorder (AjD) following an incurable cancer diagnosis. The study will consist of a combination of clinic visits and telehealth visits and will involve the following study sequence: A screening visit (approximately 3 hours): within Day-28 to -1 Visit at the clinic for continued eligibility and baseline assessments: Day -1 (1-2 hours) PAP cycle: Day 1 to Day 28 In Clinic Visits: Day 1, 13, 14, 15, 84 Telehealth appointments: Day 7, Day 21, Day 28, Day 56, Day 168 and Day 253 (Psychiatrist/Psychologist/Psychotherapist): Preparatory therapy session: Day 1, Day 7, Day 13 (approximately 1 hour) - Participants must complete three preparation sessions with the therapist in the two weeks prior to the dosing session. Two of these sessions can be completed remotely via telehealth and have flexible timing, The remote sessions can be conducted at any time between Day 1 and Day 13, provided there is at least one day between each session. One preparation session must be done in person in the dosing room, ideally during a face to face appointment at Clinic on Day 13. Participants will attend three preparatory sessions (one virtual (Day 7) telehealth and two in-person (Day 1, Day 13)) in the two weeks prior to being treated with psilocybin. The therapist will support the participant to establish intentions and goals, to be prepared for a range of potential effects of the psilocybin and have sufficient information to approach the intervention with an open mind. Face to face appointment at clinic to be conducted with a suitably trained therapist (Psychiatrist/Psychologist/Psychotherapist). Drug administration: Day 14 (approximately 8 hours). Participants will receive a single administration of PEX010 (capsule) under medical supervision on Day 14. Participants will be supported through the acute effects of the psilocybin by a suitably qualified therapist who will be present throughout the drug-assisted session. For the majority of the session the participant will be encouraged to wear a headset with a playlist and a blindfold to encourage introspection. A mouth check will be conducted to ensure compliance with dosing. Integration Session: Integration sessions will be conducted on Day 15 and Day 21 (approximately 1 hour). The Integration session on Day 15 will be a Face-to-face appointment at clinic to be conducted with a suitably trained therapist (Psychiatrist/Psychologist/Psychotherapist). An integration session conducted via telehealth with a suitably trained therapist will be conducted remotely in the two weeks following the dosing session. The integration sessions allow participants to process the experience of their drug-assisted session, consolidate changes into their perspective, reinforce insights from the therapy, and revisit issues that arose during the session. During the integration sessions, the therapist will facilitate the participant to reflect on their experiences of the psilocybin intervention, with the aim of translating their experiences into practical and accessible objectives. Follow-up: Day 84 (week 12) (Clinic visit, approximately 1 hour) Eligible non-responders at Week 12 will be offered a second PAP cycle (at 25 mg PEX010 dose level). For eligible participants the second PAP cycle will include all activities from Day 13 onwards until Day 253. A maximum of 2 PAP cycles may be administered. To be conducted with a suitably trained therapist (Psychiatrist/Psychologist/Psychotherapist). Final study follow-up Follow-up Telehealth appointments (Approximately 1 hour): Day 168 (Month 3), Day 253 (Month 6) (calculated from the 12-week visit after the final PAP). To be conducted with a suitably trained therapist (Psychiatrist/Psychologist/Psychotherapist) Session attendance checklists will be incorporated throughout the duration of the study to ensure compliance with all components of the intervention.