Clinical trial NCT06083753: Study to Evaluate the Safety and Efficacy of PIPE-307 in Subjects with Relapsing-Remitting Multiple Sclerosis
Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Multicenter Study to Evaluate the Safety and Efficacy of Oral PIPE-307 As an Adjunctive Treatment in Subjects with Relapsing-Remitting Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Relapsing Remitting Multiple Sclerosis
Keywords: Relapsing Remitting Multiple Sclerosis
PIPE 307
Multiple Sclerosis
Lead sponsor: Contineum Therapeutics
Sponsor class: INDUSTRY
First posted: 2023-10-16
Enrollment: 168
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, double-blind study of PIPE-307 or placebo in subjects with relapsing-remitting multiple sclerosis. Subjects will be randomized into 1 of 3 separate cohorts (1:1:1 randomization ratio, PIPE-307 Dose A:PIPE-307 Dose B: Placebo) for a total duration of approximately 30 weeks.

Detailed description: This is a randomized, double-blind study of PIPE-307 or placebo given to 168 subjects randomized into one of 3 separate cohorts. They will be randomized 1:1:1 (PIPE-307 Dose A:Pipe 307 Dose B: Placebo). There will be a 28-day screening period followed by a 26-week treatment period. Safety will be assessed by periodic measurements of vital signs (VS), physical (PE) and neurological examinations, electrocardiograms (ECG), blood laboratory analyses and occurrence of adverse events (AE).

Eligibility criteria: Inclusion Criteria:

* Subject is fluent in English.
* Male or female 18 to 50 years of age, inclusive, at the first Screening visit.
* A diagnosis of relapsing-remitting multiple sclerosis (RRMS) according to the 2017 Revised McDonald Criteria.
* Expanded Disability Status Scale (EDSS) and retinal nerve fiber layer within protocol requirements.
* Stable immunomodulatory treatment on no more than a single DMT for RRMS over the 6 months prior to Screening, as determined by the PI.
* Male or female subjects with reproductive potential agree to comply with a highly effective contraceptive method as per protocol through 1 month after last study drug administration as per protocol.
* General good medical health with no clinically significant or relevant abnormalities except those attributed to the underlying multiple sclerosis (MS), including medical history, physical exam, vital signs, ECG and laboratory evaluations, as assessed by the Investigator.

If enrolled in the visual evoked potential (VEP) sub-study, an additional inclusion criterion includes:

- Screening VEP P100 latency greater than the upper limit of normal (as defined in the protocol) in at least one eye, OR a protocol-defined difference in VEP P100 latency between eyes.

Exclusion Criteria:

* Diagnosis or history of symptoms of optic neuritis within 9 months prior to Screening in either eye.
* Diagnosis of MS more than 10 years prior to Screening.
* History of severe myopia, ophthalmologic or retinal disorder that would interfere with measurements of low contrast letter acuity (LCLA) or exam by optical coherence tomography (OCT), as determined by Investigator.
* Concurrent use of dalfampridine or other 4-aminopyridine or diamino-4-aminopyridine drugs.
* Clinical MS relapse or MS related treatment with corticosteroids within 6 months prior to or during Screening.
* History of treatment with bone marrow transplantation, mitoxantrone, cyclophosphamide, atacicept, or irradiation.
* Use of any daily or routine anticholinergic medications within 30 days of Screening or concurrent during the study.
* The presence of gadolinium enhancing lesions by MRI.
* Use of any drugs known to strongly or moderately induce or inhibit Cytochrome P450 3A4 (CYP3A4) enzyme activity within 30 days prior to Screening or concurrent during the study.
* Use of an investigational product, vaccine or intervention other than a non-interventional registry study within the greater of 30 days or 5 half-lives (if known) prior to Screening or expected during the study.
* History of malignancy under current active treatment or considered at substantial risk for progression or recurrence during the study interval, and/or significant cardiac disorder or dysrhythmia, as determined by the Investigator.
* History of a suicide attempt or suicidal behavior or considered at risk for suicide as judged by the PI using the Columbia-Suicide Severity Rating Scale (C-SSRS) as Screening.

If enrolled in the visual evoked potential (VEP) sub-study, an additional exclusion criterion includes:

- History of an ophthalmologic or retinal disorder that would interfere with measurements of VEP, as determined by the Investigator.

Primary outcomes:
measure: Treatment-emergent adverse events (TEAE)
timeFrame: From baseline to week 26 (end of treatment period)
measure: Change in binocular 2.5% low contrast letter acuity (LCLA)
timeFrame: From baseline to week 26 (end-of-study)
Secondary outcomes:
measure: Percentage of subjects with >/=5-letter gain in binocular 2.5% LCLA
timeFrame: From baseline to week 26
measure: Change in monocular 2.5% LCLA
timeFrame: From baseline to week 26
measure: Number of subjects with at least a 15% change in disability with the Timed 25-Foot Walk Test (T25WT)
timeFrame: From baseline to week 26
measure: Number of subjects with at least a 15% change in disability with the Nine-Hole Peg Test (9HPT)
timeFrame: From baseline to week 26
measure: Number of subjects with at least a 15% change in disability with the Symbol Digital Modality Test (SDMT)
timeFrame: From baseline to week 26
measure: Change in magnetic resonance imaging (MRI) measures of myelination and MS disease activity
timeFrame: From baseline to week 26
measure: Change in serum neurofilament light chain (NfL)
timeFrame: From baseline to week 26
measure: Pharmacokinetics: Change in blood concentration levels of PIPE-307
timeFrame: From baseline to week 30
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Xenosciences
state: Arizona
city: Phoenix
country: United States
facility: Arizona Neuroscience Research, LLC
state: Arizona
city: Berkeley
country: United States
facility: Alta Bates Summit Medical Center
state: California
city: Colorado Springs
country: United States
facility: Colorado Springs Neurological Associates
state: Colorado
city: Clearwater
country: United States
facility: MS and Neuromuscular Center of Excellence
state: Florida
city: Naples
country: United States
facility: Aqualane Clinical Research
state: Florida
city: Atlanta
country: United States
facility: Shepherd Center
state: Georgia
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Foxboro
country: United States
facility: Neurology Center of New England P.C.
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Albuquerque
country: United States
facility: University of New Mexico/Health Science Center/MIND Imaging Center/MS Specialty Clinic
state: New Mexico
city: Amherst
country: United States
facility: Dent Neurologic Institute
state: New York
city: Lake Success
country: United States
facility: Neurological Associates of Long Island, P.C.
state: New York
city: Oklahoma City
country: United States
facility: Oklahoma Research Foundation - MS Center of Excellence
state: Oklahoma
city: Knoxville
country: United States
facility: Sibyl Wray Neurology PC
state: Tennessee
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
city: Houston
country: United States
facility: Clinical Trial Network
state: Texas
city: Lubbock
country: United States
facility: Bhupesh Dihenia, MD, PA
state: Texas
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Seattle
country: United States
facility: UW Medicine MS Center
state: Washington
city: Tacoma
country: United States
facility: Multicare Neuroscience Center of Washington
state: Washington
Study officials:
affiliation: Contineum Therapeutics
name: Stephen Huhn, MD
role: STUDY_DIRECTOR
References: