A Phase 1/2a Study of Oral PRO-1562 in Healthy Subjects and Patients With Relapsing Multiple Sclerosis

Phase 1 is a randomized, double-blind, placebo-controlled, single-ascending dose (SAD) trial of PRO-1562 in healthy adult participants at a single clinical research unit to characterize the safety and pharmacokinetics of a range of oral doses of PRO-1562. Phase 2a is a randomized, double-blind, placebo-controlled, multi-center, 6-month trial of PRO-1562 in adult patients with relapsing multiple sclerosis who also have chronic optic neuropathy. Patients will remain on their stable regimen of an approved MS disease modifying therapy during the trial. Oral PRO-1562 or placebo will be dosed once a month at scheduled clinic visits. Participants will be given the option to continue on their assigned study treatment after completing the 6-month treatment period until the last patient completes the 6-month treatment period.

• PRO-1562 Oral Capsules (Drug): Oral, CNS-penetrant small molecule designed to induce remyelination
• Placebo Oral Capsule (Drug): Placebo filled capsules that look like the active intervention

Primary outcomes

• Phase 1 Incidence of ≥Grade 2 treatment-emergent adverse events [From enrollment until 7 days post dose]: Incidence of treatment-emergent adverse events including clinically significant laboratory abnormalities of ≥Grade 2 in healthy participants
• Phase 2 Change from baseline P100 VEP latency [From enrollment until the end of 6 months of treatment]: The change from baseline on visual evoked potential (VEP) in affected eye of RMS patients after 6 months of study treatment

Secondary outcomes

• Area under the concentration-time curve of PRO-1562 (Phase 1) [From enrollment until 7 days post dose.]: Concentration over time analysis to determine overall exposure to PRO-1562 by dose group
• Brain myelin content, change from baseline [From enrollment to the end of 6 months of treatment]: MRI measurement of brain myelin content in multiple brain regions will be determined as baseline and after 6 months of treatment
• Safety Phase 2 Incidence of ≥Grade 2 treatment-emergent adverse events [From enrollment until the end of 6-months of treatment]: Incidence of treatment emergent adverse events including clinically significant laboratory abnormalities of ≥Grade 2 in RMS patients

Sex: All, ages: 18 Years to 65 Years, accepts healthy volunteers

Phase 1 Inclusion Criteria:

1. Able and willing to provide written informed consent
2. Body weight ≥ 48 kg (105.6 lbs) and body mass index (BMI) ≥ 18.5 and ≤ 30 kg/m2
3. Must be in good health and without clinically significant abnormalities by review of medical and surgical history, physical examination, vital signs measurement, and 12-lead ECG
4. No clinically-significant laboratory abnormalities
5. Willing and able to use highly-effective forms of contraception for at least 30 days after the end of study visit.

Phase 1 Exclusion Criteria:

1. Ongoing medical condition requiring systemic therapy.
2. Ongoing infection
3. mRNA or live vaccine during the past 60 days
4. History of significant hypersensitivity, intolerance, or allergy to any drug/medication
5. Participation in another clinical trial with an investigational agent within 30 days prior to Check-in or 5 half-lives (if known) of the investigational drug's PK, PD, or biological activity (if known), whichever is longer
6. Positive alcohol breath test or urine screen for drugs of abuse.
7. Use or intent to use natural products or nutritional/dietary supplements (including St. John's wort), vitamins, minerals, and phytotherapeutic /herbal/plant-derived preparations within or received within 14 days or 5 half-lives prior to Check-in, whichever is longer.
8. Poor peripheral venous access.
9. Receipt of blood products within 2 months prior to Check-in.
10. Donation of blood or blood products during the 4 weeks prior to Check-in.
11. Participants who in the opinion of the Principal Investigator (or designee), should not participate in this study

• Paul A Frohna, MD, PhD, PharmD, Study chair, Progentos Therapeutics