IL-2 Plus Abatacept in FTD

NCT06395038 | Recruiting Phase 1 FDA Drug

• 1 other identifier: PRO00037661
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Neuroinflammation is a significant component of Frontotemporal Disorder (FTD). Our preliminary unpublished data demonstrated that regulatory T cells (Tregs) have a compromised phenotype and reduced suppressive function in FTD patients, skewing the immune system toward a proinflammatory status and potentially contributing to disease progression. Low dose interleukin-2 (IL-2) is now viewed as a very promising immunoregulatory drug with the capacity to selectively expand and restore functional Tregs. Our preclinical data also demonstrated synergistic effect of interleukin-2 and abatacept (CTLA4-IgG) in remodeling immunologic pathways. Abatacept is an FDA approved medication that has been indicated as a monotherapy or concomitantly with other anti-inflammatory drugs to modulate inflammation in autoimmune disorders. This study is a phase I, open-label study to assess safety and tolerability of low dose IL-2 plus abatacept immunotherapy in FTD individuals. In the first part of this study, 5 FTD patients will be recruited. These five individuals will receive subcutaneous abatacept (125 mg) followed by five-day-courses of IL-2 (1MUI/day) every four weeks for a total of 21 weeks (part-1 of the study). If the treatment strategy is safe and well-tolerated, up to 5 additional FTD subjects will be recruited to receive subcutaneous abatacept (125 mg) followed by five-day-courses of IL-2 (1MUI/day) every two weeks for a total of 21 weeks (part 2 of the study).

Conditions

Frontotemporal Degeneration

Outcome Measures

Primary Outcomes (1)

• To assess the safety and the tolerability of abatacept plus IL-2 in FTD patients

  Number of participants with adverse events and with abnormal laboratory findings (serum chemistry, hematology).

  6 months treatment phase

Secondary Outcomes (1)

• To investigate the impact of low dose IL-2 plus abatacept administration on the blood Treg population in FTD patients

  6 months treatment phase

Study Arms (2)

Abatacept plus Aldesleukin every 4 weeks

ACTIVE COMPARATOR

Subcutaneous abatacept (125 mg) followed by five-day-courses of IL-2 (1MUI/day) every four weeks will be administered for a total of 21 weeks

Drug: Abatacept plus Aldesleukin

Abatacept plus Aldesleukin every 2 weeks

ACTIVE COMPARATOR

Subcutaneous abatacept (125 mg) followed by five-day-courses of IL-2 (1MUI/day) every two weeks will be administered for a total of 21 weeks

Drug: Abatacept plus Aldesleukin

Interventions

Abatacept plus Aldesleukin DRUG

CTLA4IgG plus Low dose Interleukin-2 (Aldesleukin) administration to modify immune responses

Abatacept plus Aldesleukin every 2 weeks; Abatacept plus Aldesleukin every 4 weeks

Eligibility Criteria

• Age: 18 Years - 86 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of probable frontotemporal dementia
• Male or female age 18 to 86 years
• If on medications affecting cognition or behaviors (Such as Atypical Antipsychotics, Acetyl Choline Esterase inhibitors), participants must be on stable dosage for at least 4 weeks prior to screening and should remain at a stable dosage during the course of the study. There are no prohibited medications preventing patients from participating in the study.
• English language speaking
• Formal education of eight or more years
• Stable pharmacological treatment of any other chronic conditions for at least 30 days prior to screening
• A family member or caretaker (study partner) who is expected to be consistently available, administer study drugs of IL-2/abatacept and attend study visits throughout the study. The study partner is also supposed to provide feedback on patient's cognitive and functional status. In the event that the designated study partner is unable to continue participating in the study, the study subject should provide another suitable study partner to ensure the uninterrupted progress of the study.
• For FTD patients with limited decision-making capacity, the legally authorized representative (LAR) should be present in the decision-making process and trial participation, ensuring they understand the potential risks and benefits, and consent based on the patient's best interest. Extended time for consent will also be considered to ensure comprehension.

You may not qualify if:

• Serious, active bacterial, fungal or viral infection, active or latent tuberculosis
• History of severe pulmonary dysfunction
• History of severe cardiac dysfunction defined as left ventricular ejection fraction \<40%; a history of non-controlled cardiac arrhythmias; history of cardiac tamponade; Unstable angina or MI in the last 3 months
• Hypersensitivity or allergy to IL-2 or abatacept
• History of bowel ischemia/perforation, or GI bleeding requiring surgery
• Hospitalization or change of chronic concomitant medication within one month prior to screening.
• History of hemorrhage or infarct or \> 3 lacunar infarcts, encephalomalacia, aneurysm, vascular malformation, subdural hematoma, space-occupying lesion (e.g. abscess or brain tumor with the exception of small incidental meningiomas) in prior CT or MRI.
• Clinical or laboratory findings consistent with:
• Other primary degenerative dementia, (dementia with Lewy bodies, Alzheimer's disease, Huntington's disease, Jacob-Creutzfeld Disease, Down's syndrome, Parkinson's disease, etc.)
• Seizure disorder
• History of infectious, metabolic or systemic diseases affecting the central nervous system (syphilis, Lyme disease, other laboratory values, etc.)
• Clinically significant, advanced, or unstable disease that may interfere with outcome evaluations, such as:
• Respiratory insufficiency
• Bradycardia (\<45/min.) or tachycardia (\>100/min.)
• Poorly managed hypertension (systolic \>180 mm Hg and/or diastolic \>100 mm Hg) or hypotension (systolic \<90 mm Hg and/or diastolic \<60 mm Hg)

Sponsors & Collaborators

• The Methodist Hospital Research Institute: lead

Study Sites (1)

Houston Methodist Research Institute

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Interventions

Abatacept; aldesleukin

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Central Study Contacts

Alireza Faridar

CONTACT

2814131431; faridar99@yahoo.com

Maria B Pascual

CONTACT

bpascual@houstonmethodist.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: April 29, 2024
• First Posted: May 1, 2024
• Study Start: May 6, 2024
• Primary Completion: April 30, 2026
• Study Completion: April 30, 2026
• Last Updated: March 10, 2025

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share

Locations

US (1)