Safety of Bryostatin in Patients With MS

Multiple Sclerosis Clinical Trial

Official title:

A Single-Arm, Single-Site, Single-Dose Phase 1 Study Assessing the Safety of Bryostatin in the Treatment of Patients With Multiple Sclerosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06190912
• Other study ID #: 24-099
• Status: Recruiting
• Phase: Phase 1
• Start date: April 11, 2024
• Est. completion date: August 2026

Study information

• Verified date: May 2024
• Source: The Cleveland Clinic
• Contact: Alexis Novak
• Phone: 216-445-8597
• Email: novaka5[@]ccf.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Description:

The study is 42 weeks in duration, including safety and exploratory outcomes evaluation at 30 days after the last full assessment (Week 28) and long-term follow-up at 12 weeks after the last full assessment (Week 40). Participants will receive a total of 14 doses over 26 weeks. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: August 2026
• Est. primary completion date: April 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion

1. Written informed consent signed by participant

2. English-speaking

3. Hospital Anxiety and Depression Scale <11

4. Male and female participants, 18-60 years of age inclusive

5. 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.

6. Processing Speed Test (PST) z-score between -1.0 and -2.5

7. EDSS between 0.0 and 7.0, inclusive.

8. Adequate vision and motor function to participate in assessment procedures

9. Participants must be 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.

10. Females participating in the study must meet one the following criteria:

1. 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

2. 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 (ß-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.

11. 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

12. Participants should be in reasonably good health over the last 6 months and any chronic disease should be stable. Exclusion

1. 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

2. 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

3. Previous history of seizures or seizure disorders.

4. 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.

5. Estimated Glomerular Filtration Rate (eGFR) of <45ml/min

6. Poorly controlled diabetes (at the discretion of the Principal Investigator)

7. Use of vitamin E > 400 International Units (IU) per day within 14 days prior to screening

8. Use of valproic acid and/or lithium within 14 days prior to screening

9. Routine or intermittent use of benzodiazepines in the last year (rare use in the last year is allowed as long as use during the study is not expected).

10. Use of carbamazepine within 7 days prior to screening

11. Use of teriflunomide within 90 days prior to screening

12. Use of dalfampridine within 7 days of screening

13. Current use of acetaminophen, ciprofloxacin, and/or trimethoprim/sulfamethoxazole

14. At the discretion of the PI, any medical or psychiatric condition that is unstable or may require the initiation of additional medication or surgical intervention during the course of the study

15. Any screening laboratory values outside the laboratory reference ranges that are deemed clinically significant by the PI

16. Use of an investigational drug within 30 days prior to screening

17. Suicidality defined as active suicidal thoughts during the 6 months prior to screening or at Baseline [SBQ-R], or history of suicide attempt in previous 2 years, or at serious suicide risk in study neurologist or PI's judgment

18. Major psychiatric illness such as currently uncontrolled major depression according to Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, current or past diagnosis of bipolar disorder, schizophrenia, or any other psychiatric disorder that might interfere with the assessments of safety or efficacy at the discretion of the PI

19. Diagnosis of alcohol or drug abuse within the last 2 years

20. History of prolonged QT or prolonged QT on screening ECG [QT correction with Bazett formula (QTcB) or QT correction by Fridericia (QTcF)>499 per central reader]

21. Acute or poorly controlled medical illness: blood pressure >180 mmHg systolic or 100 mmHg diastolic; myocardial infarction within 6 months; uncompensated congestive heart failure [New York Heart Association (NYHA) Class III or IV]

22. Known to be seropositive for Hepatitis B or C, unless successful curative treatment for Hepatitis C (e.g., Harvoni) has been received, and there is documentation that there is no Hepatitis B/C virus detected 3 months after completion of treatment

23. Known to be seropositive for human immunodeficiency virus (HIV)

24. Pregnancy or breastfeeding during the study. A ß-hCG serum pregnancy test will be performed at Screening for female patients of child-bearing potential.

25. Aspartate Amino Transferase (AST) or Alanine Aminotransferase (ALT) >3x upper limit of normal (ULN) and total bilirubin >2x ULN or International Normalized Ratio (INR) >1.5

26. History of significant bleeding disorders.

27. Moderate baseline thrombocytopenia (platelets <100K/uL).

28. Elevated INR (PTT >2.0).

29. Prior exposure to bryostatin, or known sensitivity to bryostatin or any ingredient in the study drug

30. Any other concurrent medical condition, which in the opinion of the PI makes the participant unsuitable for the clinical study

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• Bryostatin 1
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.

Locations

Country	Name	City	State
United States	Cleveland Clinic	Cleveland	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Robert Fox	Synaptogenix, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory outcome: MRI Biomarkers (lesion volume)	Lesion volume	Changes from baseline to Week 11, Week 28, and Week 40
Other	Exploratory outcome: MRI Biomarkers (BPF)	Brain parenchymal fraction	Changes from baseline to Week 11, Week 28, and Week 40
Other	Exploratory outcome: MRI Biomarkers (default mode network)	Default mode network	Changes from baseline to Week 11, Week 28, and Week 40
Other	Exploratory outcome: MRI Biomarkers (microstructural complexity of dendrites and axons)	Diffusion MRI measures of tissue integrity	Changes from baseline to Week 11, Week 28, and Week 40
Other	Exploratory outcome: MRI Biomarkers (anatomical connectivity of transcallosal motor pathway)	Anatomical connectivity of transcallosal motor pathway	Changes from baseline to Week 11, Week 28, and Week 40
Other	Exploratory outcome: MRI Biomarkers (MWF)	Myelin water fraction	Changes from baseline to Week 11, Week 28, and Week 40
Other	Exploratory outcome: MRI Biomarkers (measure of myelination)	Magnetization transfer ratio	Changes from baseline to Week 11, Week 28, and Week 40
Other	Exploratory outcome: MRI Biomarkers (measure of myelination)	Quantitative T2*	Changes from baseline to Week 11, Week 28, and Week 40
Other	Exploratory outcome: MRI Biomarkers (measure of myelination)	Quantitative susceptibility mapping	Changes from baseline to Week 11, Week 28, and Week 40
Other	Exploratory outcome: MRI Biomarkers (GMA)	Grey matter atrophy	Changes from baseline to Week 11, Week 28, and Week 40
Other	Exploratory outcome: MRI Biomarkers (GMF)	Grey matter fraction	Changes from baseline to Week 11, Week 28, and Week 40
Other	Exploratory outcome: MRI Biomarkers (WMF)	White matter fraction	Changes from baseline to Week 11, Week 28, and Week 40
Other	Exploratory outcome: MRI Biomarkers (CA)	Cortical atrophy	Changes from baseline to Week 11, Week 28, and Week 40
Other	Exploratory Outcome: MoCA	Montreal Cognitive Assessment test	Changes from baseline to Week 11, Week 28, and Week 40
Other	Exploratory Outcome: EDSS	Expanded Disability Status Scale	Changes from baseline to Week 11, Week 28, and Week 40
Other	Exploratory Outcomes: MS Performance Test Domains (Lower Extremity)	Walking Speed Test (WST)	Changes from baseline to Week 11, Week 28, and Week 40
Other	Exploratory Outcomes: MS Performance Test Domains (Upper Extremity)	Manual dexterity test (MDT)	Changes from baseline to Week 11, Week 28, and Week 40
Other	Exploratory Outcomes: MS Performance Test Domains (Cognition)	Processing speed test (PST)	Changes from baseline to Week 11, Week 28, and Week 40
Other	Exploratory Outcomes: Quality of life (NEURO-QoL)	Quality of Life in Neurological Disorders (NEURO-QoL)	Changes from baseline to Week 11, Week 28, and Week 40
Other	Exploratory Outcomes: CVLT3	California Verbal Learning Test 3rd Edition (CVLT3)	Change from baseline to Week 28 and Week 40
Other	Exploratory Outcomes: BVMT-R	Brief Visuospatial Memory Test - Revised (BVMT-R)	Change from baseline to Week 28 and Week 40
Other	Exploratory Outcomes: JOLO	Judgement of Line Orientation (JOLO)	Change from baseline to Week 28 and Week 40
Other	Exploratory Outcomes: BNT	Boston Naming Test (BNT)	Change from baseline to Week 28 and Week 40
Other	Exploratory Outcomes: D-KEFS (Sorting)	Delis-Kaplan Executive Function System (D-KEFS) Sorting Test	Change from baseline to Week 28 and Week 40
Other	Exploratory Outcomes: COWAT	Controlled Oral Word Association Test	Change from baseline over 40 weeks
Primary	Adverse Events	Frequency of Adverse Events [Treatment Emergent AEs (TEAEs), Serious Adverse Events (SAEs), and Suspected Unexpected Serious Adverse Reactions (SUSARS)]	Over 40 weeks
Primary	Study Medication Discontinuation	Frequency of study medication discontinuation and reason thereof	Over 40 weeks
Primary	CNS inflammatory effects	Potential CNS inflammatory effects as captured by clinical monitoring and MRI	Over 40 weeks