Multiple Sclerosis
Conditions
Keywords
relapsing multiple sclerosis, chronic optic neuropathy, Remyelination
Brief summary
Phase 1 will test single oral doses of PRO-1562 in healthy adult subjects to characterize the safety and the amount of drug that is absorbed into the body. Some subjects will have lumbar punctures performed to measure the amount of drug that crosses the blood-brain barrier since that is the site of drug activity. Phase 2a will be a 6-month trial to test the ability of once monthly dosing of PRO-1562 to promote remyelination of the CNS and provide clinical benefit to adult patients with relapsing multiple sclerosis (RMS) who also have long-term vision problems diagnosed as chronic optic neuropathy. The benefits of remyelination will be measured using tests of visual acuity, speed of optic nerve conduction signals, and clinical assessments of cognitive and motor function. PRO-1562 will be added on to a stable regimen of MS disease modifying therapy.
Detailed description
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.
Interventions
DRUGPRO-1562 Oral Capsules
Oral, CNS-penetrant small molecule designed to induce remyelination
DRUGPlacebo Oral Capsule
Placebo filled capsules that look like the active intervention
Sponsors
Progentos Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Australia
Contacts
CONTACTChief Medical Officer
STUDY_CHAIRPaul A Frohna, MD, PhD, PharmD
Progentos Therapeutics
Outcome results
None listed