ERG/5-HTP in Fragile X Syndrome (FXS)

NCT05030129 | Completed Phase 2 Results FDA Drug

• 1 other identifier: ORA 21051102
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the safety, tolerability and efficacy of Ergoloid mesylates (EM) and 5-hydroxytryptophan (5-HTP) and the combination (EM + 5-HTP) compared to placebo in males aged 18-45 years old with Fragile X Syndrome.

Conditions

Fragile X Syndrome

Outcome Measures

Primary Outcomes (2)

• Safety and Tolerability - Number of Treatment-Emergent Adverse Events

  Adverse Events (AEs), including clinically meaningful laboratory abnormalities and significant behavioral changes will be recorded from the time of the subject's first dose of study drug to the end of the study (Week 17) or longer if needed. Adverse events will be assessed at each visit as well as during each phone call and will be tabulated for each treatment period.

  Baseline through Week 17

• Safety and Tolerability - Severity of Treatment Emergent Adverse Events

  Adverse Events (AEs), including clinically meaningful laboratory abnormalities and significant behavioral changes will be tabulated for each treatment period. The Investigator is responsible for assessing the severity (intensity) of each adverse event as mild, moderate, or severe according to the following definitions: Mild - An event that is easily tolerated and generally not interfering with normal daily activities. Moderate - An event that is sufficiently discomforting to interfere with normal daily activities. Severe - An event that is incapacitating with inability to work or perform normal daily activities.

  Baseline through Week 17

Secondary Outcomes (16)

• Change From Baseline in KiTAP Executive Battery - Alertness Subscore (Reaction Time)

  Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment)

• Change From Baseline in Total Number of Correct Responses on KiTAP Executive Battery Distractibility Subtest

  Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment)

• Change From Baseline in Total Number of Errors on KiTAP Executive Battery Distractibility Subtest

  Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment)

• Change From Baseline in Total Number of Correct Responses on KiTAP Executive Battery Flexibility Subtest

  Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment)

• Change From Baseline in Total Number of Errors on KiTAP Executive Battery Flexibility Subtest

  Baseline, Week 4 (EM Treatment), Week 8 (EM+5-HTP Treatment), Week 12 (5-HTP Treatment), Week 16 (Placebo Treatment)

Study Arms (4)

Ergoloid mesylates (EM)

EXPERIMENTAL

During treatment period 1, subjects will receive EM 1 mg (Medisca) and matching placebo for 5-HTP 100mg (ascorbic acid powder). One of each capsule (both size 00) will be taken three times per day for four weeks.

Drug: Ergoloid Mesylates; Drug: Matching placebo for 5-Hydroxytryptophan

Ergoloid mesylates (EM) and 5-hydroxytryptophan (5-HTP)

EXPERIMENTAL

During treatment period 2, subjects will receive EM 1 mg (Medisca) and 5-HTP 100 mg (5-HTP, Basic Vitamins). One of each capsule (both size 00) will be taken three times per day for four weeks.

Drug: 5-Hydroxytryptophan; Drug: Ergoloid Mesylates

5-hydroxytryptophan (5-HTP)

EXPERIMENTAL

During treatment period 3, subjects will receive 5-HTP 100 mg (5-HTP, Basic Vitamins) and matching placebo for EM 1 mg (ascorbic acid powder). One of each capsule (both size 00) will be taken three times per day for four weeks.

Drug: 5-Hydroxytryptophan; Drug: Matching placebo for Ergoloid mesylates

Placebo

PLACEBO COMPARATOR

During treatment period 4, subjects will receive matching placebo for EM 1mg (ascorbic acid powder) and matching placebo for 5-Hydroxytryptophan 100mg (ascorbic acid powder). One of each capsule (both size 00) will be taken three times per day for four weeks.

Drug: Matching placebo for Ergoloid mesylates; Drug: Matching placebo for 5-Hydroxytryptophan

Interventions

5-Hydroxytryptophan DRUG

5-HTP will be over-encapsulated in identical size 00 capsules. During the 5-HTP Treatment Period (Period 3) and 5-HTP/EM Treatment Period (Period 2), subjects will take 1 capsule of 5-HTP 3 times per day.

Also known as: 5-HTP, Basic Vitamins

5-hydroxytryptophan (5-HTP); Ergoloid mesylates (EM) and 5-hydroxytryptophan (5-HTP)

Ergoloid Mesylates DRUG

Ergoloid mesylates 1 mg will be mixed with methyl cellulose and placed in a size 00 capsule. During the EM Treatment Period (Period 1) and 5-HTP/EM Treatment Period (Period 2), subjects will take 1 capsule of EM 3 times per day.

Also known as: Medisca

Ergoloid mesylates (EM); Ergoloid mesylates (EM) and 5-hydroxytryptophan (5-HTP)

Matching placebo for Ergoloid mesylates DRUG

Matching placebo for Ergoloid mesylates will be ascorbic acid powder in identical size 00 capsules. During the 5-HTP Treatment Period (Period 3) and Placebo Treatment Period (Period 4), subjects will take 1 capsule of matching placebo for EM 3 times per day.

5-hydroxytryptophan (5-HTP); Placebo

Matching placebo for 5-Hydroxytryptophan DRUG

Matching placebo for 5-Hydroxytryptophan will be ascorbic acid powder in identical size 00 capsules. During the EM Treatment Period (Period 2) and Placebo Treatment Period (Period 4), subjects will take 1 capsule of matching placebo for 5-HTP 3 times per day.

Ergoloid mesylates (EM); Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male aged 18 to 45 years, inclusive.
• Participant has Fragile X Syndrome with a molecular genetic confirmation of the full Fragile X Mental Retardation (FMR1) mutation (≥200 CGG repeats).
• Current treatment with no more than 3 prescribed psychotropic medications. Anti-epileptic medications are permitted and are not counted as psychotropic medications if they are used for treatment of seizures. Anti-epileptics for other indications, such as the treatment of mood disorders, count towards the limit of permitted medications.
• Permitted concomitant psychotropic medications must be at a stable dose and dosing regimen for at least 2 weeks prior to Screening and must remain stable during the period between Screening and the commencement of study medication.
• Anti-epileptic medications must be at a stable dose and dosing regimen for 12 weeks prior to Screening and must remain stable during the period between Screening and the commencement of study medication.
• Participants with a history of seizure disorder who are currently receiving treatment with anti-epileptics must have been seizure-free for 3 months preceding screening, or must be seizure-free for 3 years if not currently receiving anti-epileptics.
• Participant must be willing to practice barrier methods of contraception while on study, if sexually active. Abstinence is also considered a reasonable form of birth control in this study population.
• Participant has a parent, legal authorized guardian or consistent caregiver.
• Participant and caregiver are able to attend the clinic regularly and reliably.
• Participant is able to swallow capsules.
• For participants who are not their own legal guardian, participant's parent/legal authorized guardian is able to understand and sign an informed consent form to participate in the study.
• If participant is his own legal guardian, he can understand and sign informed consent to participate in the study.
• If participant is not their own legal guardian, the participant provides assent for participation in the study, if the participant has the cognitive ability to provide assent.

You may not qualify if:

• History of, or current cardiovascular, renal, hepatic, respiratory, gastrointestinal, psychiatric, neurologic, cerebrovascular, or other systemic disease that would place the participant at risk or potentially interfere with the interpretation of the safety, tolerability, or efficacy of the study medication.
• Common diseases such as mild hypertension, well-controlled type 2 diabetes mellitus (hemoglobin A1C \[Hgb A1C\] \<6.5%), etc. are allowed per the investigator's judgment as long as they are stable and controlled by medical therapy that is constant for at least 4 weeks before randomization.
• Clinically significant abnormalities, in the investigator's judgment, in safety laboratory tests, vital signs, as measured during Screening.
• History of substance abuse within the past year, according to investigator assessment.
• Use of CYP3A4 inhibitors, beta-blockers, MAO inhibitors or triptans at any time during participation in the study.
• Significant hearing or visual impairment that may affect the participant's ability to complete the test procedures.
• Concurrent major psychiatric condition (e.g., Major Depressive Disorder, Schizophrenia or Bipolar Disorder) as diagnosed by the investigator. Participants with additional diagnosis of Autism Spectrum Disorder or Anxiety Disorder will be allowed as these are characteristics of FXS.
• Participant has active diseases that would interfere with participation, such as acquired immunodeficiency disorder, hepatitis C, hepatitis B, or tuberculosis.
• Participant is planning to commence psychotherapy or cognitive behavior therapy (CBT) during the period of the study or had begun psychotherapy or CBT within 4 weeks prior to Screening.
• Participant has participated in another clinical trial within the 30 days preceding Screening.

Sponsors & Collaborators

• Elizabeth Berry-Kravis: lead
• FRAXA Research Foundation: collaborator
• Purposeful IKE: collaborator

Study Sites (1)

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

MeSH Terms

Conditions

Fragile X Syndrome

Interventions

5-Hydroxytryptophan; Ergoloid Mesylates

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Sex Chromosome Disorders; Chromosome Disorders; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Heredodegenerative Disorders, Nervous System

Intervention Hierarchy (Ancestors)

Tryptophan; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Dihydroergotoxine; Ergotamines; Ergot Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Elizabeth Berry-Kravis, MD PhD
• Organization: Rush University Medical Center

Elizabeth_Berry-Kravis@rush.edu

312-942-4036

Study Officials

• Elizabeth Berry-Kravis, MD, PhD

  Rush University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: This is a single-blind study, meaning the participant and his family/caregivers will not know what drug or combination the participant is receiving during each time period. The investigator and study coordinator will know what drug the participant is taking. The remainder of the study team performing assessments such as the Vineland, eye tracking, ERP, Toolbox, and the KiTAP will not know the type of treatment the patient is on when testing is done.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Department of Pediatrics, Neurological Sciences, Biochemistry

Model Details: This study will use a single-blind, 4-period sequential design. Fifteen participants with Fragile X Syndrome ages 18-45 years will enter a Screening period of up to 28 days followed by four 4 week single-blind treatment periods (summarized below). * Period 1: Ergoloid mesylates 1 mg and matching placebo for 5-Hydroxytryptophan 100 mg, taken three times per day * Period 2: Ergoloid mesylates 1 mg and 5-Hydroxytryptophan 100 mg, taken three times per day * Period 3: 5-Hydroxytryptophan 100 mg and matching placebo for Ergoloid mesylates 1mg, taken three times per day * Period 4: Matching placebo for Ergoloid mesylates 1mg and matching placebo for 5- Hydroxytryptophan 100mg, taken three times per day

Study Record Dates

• First Submitted: August 5, 2021
• First Posted: September 1, 2021
• Study Start: October 7, 2021
• Primary Completion: January 19, 2023
• Study Completion: January 19, 2023
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-08

Locations

US (1)