The first participant in the RECONNECT phase 2 clinical trial has been dosed with RE104 for the treatment of postpartum depression (PPD), according to Reunion Neuroscience Inc.1
Takeaways
- The first participant has been dosed in the RECONNECT Phase 2 clinical trial for RE104, targeting postpartum depression (PPD).
- RE104, a prodrug of 4-OH-DiPT, offers a psychedelic experience lasting 3 to 4 hours, about half the duration of psilocybin, with similar intensity and safety outcomes.
- The trial aims to evaluate changes in depression severity using the Montgomery-Åsberg Depression Rating Scale from baseline to day 7 as the primary outcome, with additional measurements at days 1, 14, and 28.
- Participants must be within 12 months postpartum, meet DSM-5 criteria for PPD, and adhere to specific health and treatment guidelines; those with certain psychiatric conditions, significant suicide risk, or prior psychedelic use are excluded.
- This double-blind, randomized, multicenter trial began in June 2024 and is expected to complete by June 2025, with Reunion Neuroscience aiming to develop effective treatments for underserved mental health disorders.
PPD is one of the most common disorders of pregnancy, with approximately 10% to 15% of all mothers affected. Women and their families are often severely impacted by PPD. Symptoms include significant mood, appetite, and sleep changes leading to lack of concentration, feelings of hopelessness, poor self-esteem, loss of energy, and maternal disinterest.
According to the Centers for Disease Control and Prevention, mental health conditions are the leading cause of pregnancy-related death during the first year postpartum. This indicates a need for a treatment option with faster onset and greater efficacy after a single dose.
RE104, a prodrug of 4-OH-DiPT, was designed for use as a short duration psychedelic experience. Similar psychedelic outcomes in intensity and quality were observed from use of RE104 in a phase 1 clinical trial when compared to psilocybin, a longer duration psychedelic.
At 3 to 4 hours, the psychedelic effect of RE104 lasted approximately half as long as that of psilocybin. Similar, favorable safety outcomes were also observed between the 2 methods. RE104 is also being evaluated for use in patients with other neuropsychiatric indications such as adjustment disorder in cancer patients.
The safety and efficacy of a single subcutaneous dose of RE104 against moderate-to-severe PPD in adult women is being evaluated in the RECONNECT phase 2 trial. It is a multicenter, randomized, double-blind, parallel-group, active dose-controlled clinical trial with the change in depression severity from baseline to day 7 as the primary outcome.
Depression severity is being measured using patients’ total Montgomery-Åsberg Depression Rating Scale (MADRS) score. MADRS is a 10-item clinician rated scale for depression severity.
Secondary outcomes include change in MADRS score at days 1, 14, and 28, MADRS response indicating at least a 50% reduction in symptoms, and MADRS remission with a score of 10 or less. The safety and tolerability of RE104 will also be reported.
Inclusion criteria for the RECONNECT trial include being 12 months or under postpartum at screening, meeting DSM-5 criteria for PPD, having a Hamilton Depression Scale total score meeting the severity threshold at screening and baseline, not using any psychotropic medication or psychotherapy in the 30 days before screening, ceasing breastfeeding at screening, and having a negative pregnancy test at screening.2
Exclusion criteria include history or active postpartum psychosis, history of treatment-resistant depression, significant suicide risk, active or medical history of certain psychiatric conditions, medically significant condition, receiving electroconvulsive therapy within 90 days before screening, prior psychedelic use, and prior use or need for prohibited medications.
In the comparator group, RE104 is administered in a 1.5 mg dosage, compared to a 30 mg dosage in the experimental group. Both groups receive the treatment through a single, subcutaneous dose.
The study began on June 14, 2024, with completion estimated for June 2025. It marks a step in Reunion Neuroscience’s goal of developing therapeutic solutions for underserved mental health disorders.1
References
- Reunion Neuroscience Inc. announces first patient dosed in phase 2 clinical trial of RE104 for the treatment of postpartum depression. Reunion Neuroscience. July 23, 2024. Accessed July 23, 2024. https://reunionneuro.com/2024/07/23/reunion-neuroscience-inc-announces-first-patient-dosed-in-phase-2-clinical-trial-of-re104-for-the-treatment-of-postpartum-depression/
- RE104 Safety and Efficacy Study in Postpartum Depression. Clinical Trials. March 26, 2024. Accessed July 23, 2024. https://clinicaltrials.gov/study/NCT06342310#study-record-dates
