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

Primary Purpose

Amyotrophic Lateral Sclerosis

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

[11C]CPPC Injection

About this trial

This is an interventional diagnostic trial for Amyotrophic Lateral Sclerosis focused on measuring Positron Emission Tomography

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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:
1. Coagulopathy
2. 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:
1. Current drug abuse or alcoholism
2. Unstable medical conditions
3. Unstable psychiatric illness including psychosis and untreated major depression within 90 days of screening

Sites / Locations

Johns Hopkins Outpatient Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Participants with diagnosis of ALS

Healthy Participants without a diagnosis of ALS

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

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.

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.

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.

Secondary Outcome Measures

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

Sensitivity of use of [11C]CPPC in PET neuroimaging to detect ALS will be determined by comparing the PET images from patients with ALS with those from healthy controls.

Full Information

NCT ID

NCT04749433

First Posted

January 29, 2021

Last Updated

July 7, 2023

Sponsor

Johns Hopkins University

Collaborators

Precision Molecular

1. Study Identification

Unique Protocol Identification Number

NCT04749433

Brief Title

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

Official Title

A Phase 1 Study to Assess the Safety and Tolerability of PET Imaging With [11C]CPPC [5-cyano-N-(4-(4-[11C]Methylpiperazin-1-yl)-2-(Piperidin-1-yl)Phenyl)Furan-2-carboxamide] Radioligand in Patients With Amyotrophic Lateral Sclerosis

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Terminated

Why Stopped

study stopped to enhance protocol and resume under different sponsor

Study Start Date

September 1, 2021 (Actual)

Primary Completion Date

March 30, 2023 (Actual)

Study Completion Date

March 30, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Johns Hopkins University

Collaborators

Precision Molecular

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

Detailed Description

This is a Phase 1 study of safety and tolerability of an investigational radiotracer drug called [5-cyano-N-(4-(4-[11C]Methylpiperazin-1-yl)-2-(Piperidin-1-yl)Phenyl)Furan-2-carboxamide] ([11C]CPPC). A radiotracer is a substance that chemically marks certain structures in the body. In this case, [11C]CPPC highlights structures expressing colony stimulating factor receptor (CSF1R), a receptor that is expressed on microglial cells. A safety and tolerability study is looking to see if there are any unanticipated, possibly harmful, effects of the use of the radiotracer in humans. However, ultimately, the investigators would like to know if this drug can be used to make better images of the brain for patients with amyotrophic lateral sclerosis (ALS), which could help doctors better understand the disease and help take care of patients with ALS. This study will use a radiotracer to look for a chemical receptor which ALS patients have more of in the brain. After receiving the radiotracer, participants' brains will be scanned with a positron emission tomography (PET) imaging machine.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Amyotrophic Lateral Sclerosis

Keywords

Positron Emission Tomography

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Model Description

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.

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

4 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Participants with diagnosis of ALS

Arm Type

Experimental

Arm Description

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.

Arm Title

Healthy Participants without a diagnosis of ALS

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

[11C]CPPC Injection

Other Intervention Name(s)

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

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Up to 10 days follow up after scan

Title

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

Description

Time Frame

Baseline and 10 days after scan

Title

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

Description

Time Frame

Baseline and 10 days after scan

Title

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

Description

Time Frame

Baseline and 10 days after scan

Secondary Outcome Measure Information:

Title

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

Description

Sensitivity of use of [11C]CPPC in PET neuroimaging to detect ALS will be determined by comparing the PET images from patients with ALS with those from healthy controls.

Time Frame

1 day

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Nicholas J Maragakis, MD

Organizational Affiliation

Johns Hopkins University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Johns Hopkins Outpatient Center

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21287

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

30635412

Citation

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.

Results Reference

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

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