Clinical trial NCT04749433: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Amyotrophic Lateral Sclerosis
Keywords: Positron Emission Tomography
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: Precision Molecular
First posted: 2021-02-11
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. Men and women at least 18 years old.
3. 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).
4. Geographic accessibility to the study center and the ability to travel to the clinic for study visits.
5. Presence of a willing and able caregiver.
6. 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
7. 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.
8. Agrees to the visit schedule as outlined in the informed consent.
9. Pre-study labs within normal range, or if abnormal, deemed not clinically significant by the site investigator.

Exclusion Criteria:

1. Weakness due to causes other than ALS.
2. Receipt of any investigational drug, device or biologic within 30 days of administration of study compound.
3. Use of anti-inflammatory medications, immunosuppressants, or benzodiazepines.
4. Any concomitant medical disease or condition limiting the safety to participate including, but not limited to:

   1. Coagulopathy
   2. Active infection
5. Any condition that the site PI feels may interfere with participation in the study
6. Inability to provide informed consent as determined by the site PI.
7. Known clinical evidence of frontotemporal dementia
8. Inadequate family or caregiver support as determined by the site PI.
9. 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

Primary outcomes:
measure: Safety of use of [11C]CPPC in patients with ALS as assessed by adverse events
timeFrame: Up to 10 days follow up after scan
measure: Safety of use of [11C]CPPC in patients with ALS as assessed by a change in neurological status
timeFrame: Baseline and 10 days after scan
measure: Safety of use of [11C]CPPC in patients with ALS as assessed by a change in complete blood count (CBC) test
timeFrame: Baseline and 10 days after scan
measure: Safety of use of [11C]CPPC in patients with ALS as assessed by a change in complete metabolic panel (CMP) test
timeFrame: Baseline and 10 days after scan
Secondary outcomes:
measure: Sensitivity of use of [11C]CPPC as assessed by a radiologist
timeFrame: 1 day
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Outpatient Center
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Nicholas J Maragakis, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.