Safety of Bryostatin in Patients With MS

NCT06190912 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: 24-099
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-site, single-arm, single-dose, Phase 1 study of the safety of bryostatin in participants with multiple sclerosis (MS) receiving any disease modifying therapy (DMT).

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (3)

• Adverse Events

  Frequency of Adverse Events \[Treatment Emergent AEs (TEAEs), Serious Adverse Events (SAEs), and Suspected Unexpected Serious Adverse Reactions (SUSARS)\]

  Approximately 37 weeks

• Study Medication Discontinuation

  Frequency of study medication discontinuation and reason thereof

  Approximately 37 weeks

• CNS Inflammatory Effects

  Potential CNS inflammatory effects as captured by clinical monitoring and MRI

  Approximately 37 weeks

Study Arms (1)

Bryostatin 1

EXPERIMENTAL

Participants in this arm will receive treatment with Bryostatin 1

Drug: Bryostatin 1

Interventions

Bryostatin 1 DRUG

Eligible participants will be treated with bryostatin over a 26-week period. Doses 1, 2, 8, and 9 of the study drug will be a loading dose 20% higher (i.e., 24 µg) than the assigned fixed dose and will be administered one week apart. Otherwise, the assigned fixed dose is 20 µg. Drug is administered intravenously (IV) by continuous infusion over 45(±5) minutes. Participants are scheduled to receive 14 doses over 26 weeks.

Bryostatin 1

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent signed by participant
• English-speaking
• Hospital Anxiety and Depression Scale \<11
• Male and female participants, 18-65 years of age inclusive
• Established diagnosis of MS, as defined by the 2017 revision of McDonald Diagnostic Criteria (any form of MS). A diagnosis of MS must be confirmed at the time of the screening visit.
• Processing Speed Test (PST) z-score between -1.0 and -2.5
• EDSS between 0.0 and 7.0, inclusive.
• Adequate vision and motor function to participate in assessment procedures
• Participants must be off of a DMT or on a stable dose of a DMT for at least 1 year prior to entry into the study, and the dose should not change during the study unless a change is required by a clinically significant change in the participant's status.
• Females participating in the study must meet one the following criteria:
• Surgically sterilized (e.g., hysterectomy, bilateral oophorectomy or tubal ligation) for at least 6 months or postmenopausal (postmenopausal females must have no menstrual bleeding for at least 1 year) or
• If not postmenopausal, agree to use a double method of contraception, one of which is a barrier method (e.g., intrauterine device plus condom, spermicidal gel plus condom) 30 days prior to dosing until 30 days after last dose and have negative human chorionic gonadotropin (β-hCG) test for pregnancy at screening. Contraception methods resulting in an overall failure rate of \<1 % per year are required for women of childbearing potential.
• Males who have not had a vasectomy must use appropriate contraception methods (barrier or abstinence) from 30 days prior to dosing until 30 days after last dose
• Participants should be in reasonably good health over the last 6 months and any chronic disease should be stable.

You may not qualify if:

• Evidence of significant CNS vascular disease on previous neuroimaging, including but not limited to cortical stroke, multiple infarcts, localized single infarcts in the thalamus, angular gyrus, multiple lacunar infarcts, or extensive white matter injury
• Clinically significant neurologic disease or condition other than MS, such as cerebral tumor, chronic subdural fluid collections, Huntington's Disease, Parkinson's Disease, normal pressure hydrocephalus, or any other diagnosis that could interfere with assessment of safety and efficacy
• Previous history of seizures or seizure disorders.
• Evidence of clinically significant unstable cardiovascular, pulmonary, renal, hepatic, gastrointestinal, neurologic, or metabolic disease within the 6 months prior to enrollment. If there is a history of cancer, the participant should be clear of cancer for at least 2 years prior to screening. More recent history of basal cell or squamous cell carcinoma and melanoma in situ (Stage 0) may be acceptable after review by the Medical Monitor.
• Estimated Glomerular Filtration Rate (eGFR) of \<45ml/min
• Poorly controlled diabetes (at the discretion of the Principal Investigator)
• Use of vitamin E \> 400 International Units (IU) per day within 14 days prior to screening
• Use of valproic acid and/or lithium within 14 days prior to screening
• Use of carbamazepine within 7 days prior to screening
• Use of teriflunomide within 90 days prior to screening
• Use of dalfampridine within 7 days of screening
• Current use of acetaminophen, ciprofloxacin, and/or trimethoprim/sulfamethoxazole
• Use of any potent or moderate inhibitor or inducer of CYP3A4, CYP2C8, or CYP2C9. Concomitant medicines will be examined on a case-by-case basis against the Flockhart Table by study investigator, and if needed, the Medical Monitor, to determine allowability
• Current use of St. John's Wort, within 2 weeks prior to screening
• Consumption of grapefruit juice from screening until end of study

Sponsors & Collaborators

• Robert Fox: lead
• Synaptogenix, Inc.: collaborator

Study Sites (1)

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

bryostatin 1

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Limitations and Caveats

The study funder abruptly withdrew funding and access to bryostatin shortly after the 4th participant was enrolled. As a result, detailed safety and efficacy analyses were not able to be performed effectively. There were no concerning adverse events or other safety signals observed. The exploratory efficacy measures were limited due to small sample size. The number of participants evaluated were too few to draw any meaningful conclusions.

Results Point of Contact

• Title: Dr. Robert Fox
• Organization: Cleveland Clinic Foundation

foxr@ccf.org

216 445-1915

Study Officials

• Robert J Fox, MD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Vice Chair for Research, Neurological Institute, Staff Neurologist, Cleveland Clinic Mellen Center for MS Treatment and Research

Study Record Dates

• First Submitted: December 11, 2023
• First Posted: January 5, 2024
• Study Start: June 26, 2024
• Primary Completion: March 15, 2025
• Study Completion: March 15, 2025
• Last Updated: March 31, 2026
• Results First Posted: March 31, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)