Study of [11C]CPPC to Assess the Safety and Tolerability in Patients With ALS

NCT04749433 | Terminated Phase 1 FDA Drug

• 1 other identifier: IRB00263068
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to evaluate the safety of using the \[5-cyano-N-(4-(4-\[11C\]Methylpiperazin-1-yl)-2-(Piperidin-1-yl)Phenyl)Furan-2-carboxamide\] (\[11C\]CPPC) radiotracer in positron emission tomography (PET) imaging of people with amyotrophic lateral sclerosis (ALS). The investigators are also interested to see whether use of this radiotracer reveals imaging differences between patients with ALS and healthy patients.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Positron Emission Tomography

Outcome Measures

Primary Outcomes (4)

• Safety of use of [11C]CPPC in patients with ALS as assessed by adverse events

  Safety of use of \[11C\]CPPC in positron emission tomography (PET) neuroimaging of patients with a diagnosis of ALS. Safety will be assessed by number of adverse events during and 10 days after the injection.

  Up to 10 days follow up after scan

• Safety of use of [11C]CPPC in patients with ALS as assessed by a change in neurological status

  Safety of use of \[11C\]CPPC in positron emission tomography (PET) neuroimaging of patients with a diagnosis of ALS. Safety will be assessed by neurological physical exam to determine if there is a change in the findings from baseline.

  Baseline and 10 days after scan

• Safety of use of [11C]CPPC in patients with ALS as assessed by a change in complete blood count (CBC) test

  Safety of use of \[11C\]CPPC in positron emission tomography (PET) neuroimaging of patients with a diagnosis of ALS. Safety will be assessed by monitoring of the complete blood count (CBC) for a change from baseline that is outside of the normal range.

  Baseline and 10 days after scan

• Safety of use of [11C]CPPC in patients with ALS as assessed by a change in complete metabolic panel (CMP) test

  Safety of use of \[11C\]CPPC in positron emission tomography (PET) neuroimaging of patients with a diagnosis of ALS. Safety will be assessed by a change in the CMP from baseline that is outside of the normal range.

  Baseline and 10 days after scan

Secondary Outcomes (1)

• Sensitivity of use of [11C]CPPC as assessed by a radiologist

  1 day

Study Arms (2)

Participants with diagnosis of ALS

EXPERIMENTAL

Participants with a diagnosis of ALS will receive a single dose of \[11C\]CPPC (370 megabecquerel (MBq) (X±1 mCi)) intravenously and subsequent positron emission tomography (PET) scan.

Drug: [11C]CPPC Injection

Healthy Participants without a diagnosis of ALS

EXPERIMENTAL

Healthy participants (without a diagnosis of ALS) will receive a single dose of \[11C\]CPPC (370 megabecquerel (MBq) (X±1 mCi)) intravenously and subsequent positron emission tomography (PET) scan.

Drug: [11C]CPPC Injection

Interventions

[11C]CPPC Injection DRUG

A single dose of \[11C\]CPPC (370 megabecquerel (MBq) (X±1 mCi)) intravenously and subsequent positron emission tomography (PET) scan.

Also known as: [5-cyano-N-(4-(4-[11C]methylpiperazin-1-yl)-2-(piperidin-1-yl)phenyl)furan-2-carboxamide]

Healthy Participants without a diagnosis of ALS; Participants with diagnosis of ALS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have the ability to understand the requirements of the study, provide written informed consent, understand and provide written authorization for the use and disclosure of Protected Health Information (PHI) \[per Health Insurance Portability and Accountability Act (HIPAA) Privacy Ruling\] and comply with the study procedures.
• Men and women at least 18 years old.
• Women must have a negative serum pregnancy test and practice an acceptable method of contraception or be of non-childbearing potential (post-menopausal for at least 2 years or who have undergone hysterectomy, oophorectomy or surgical sterilization).
• Geographic accessibility to the study center and the ability to travel to the clinic for study visits.
• Presence of a willing and able caregiver.
• Diagnosis of ALS based on examination by the site PI, meeting El Escorial criteria for possible, laboratory-supported probable, probable or definite ALS or be a person without a diagnosis of ALS disorder
• Vital capacity ≥ 50% of predicted normal for age, height and gender measured in the seated position and the ability to lie supine for a period of 1 hour.
• Agrees to the visit schedule as outlined in the informed consent.
• Pre-study labs within normal range, or if abnormal, deemed not clinically significant by the site investigator.

You may not qualify if:

• Weakness due to causes other than ALS.
• Receipt of any investigational drug, device or biologic within 30 days of administration of study compound.
• Use of anti-inflammatory medications, immunosuppressants, or benzodiazepines.
• Any concomitant medical disease or condition limiting the safety to participate including, but not limited to:
• Coagulopathy
• Active infection
• Any condition that the site PI feels may interfere with participation in the study
• Inability to provide informed consent as determined by the site PI.
• Known clinical evidence of frontotemporal dementia
• Inadequate family or caregiver support as determined by the site PI.
• Presence of any of the following conditions:
• Current drug abuse or alcoholism
• Unstable medical conditions
• Unstable psychiatric illness including psychosis and untreated major depression within 90 days of screening

Sponsors & Collaborators

• Johns Hopkins University: lead
• Precision Molecular: collaborator

Study Sites (1)

Johns Hopkins Outpatient Center

Baltimore, Maryland, 21287, United States

Location

Related Publications (1)

• Horti AG, Naik R, Foss CA, Minn I, Misheneva V, Du Y, Wang Y, Mathews WB, Wu Y, Hall A, LaCourse C, Ahn HH, Nam H, Lesniak WG, Valentine H, Pletnikova O, Troncoso JC, Smith MD, Calabresi PA, Savonenko AV, Dannals RF, Pletnikov MV, Pomper MG. PET imaging of microglia by targeting macrophage colony-stimulating factor 1 receptor (CSF1R). Proc Natl Acad Sci U S A. 2019 Jan 29;116(5):1686-1691. doi: 10.1073/pnas.1812155116. Epub 2019 Jan 11.

  PMID: 30635412 BACKGROUND

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Nicholas J Maragakis, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: There will be two groups of participants in this study, healthy control participants and participants with a diagnosis of ALS. All patients will receive the same radiotracer and scan.

Study Record Dates

• First Submitted: January 29, 2021
• First Posted: February 11, 2021
• Study Start: September 1, 2021
• Primary Completion: March 30, 2023
• Study Completion: March 30, 2023
• Last Updated: October 8, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)