MCLENA-1: A Clinical Trial for the Assessment of Lenalidomide in Amnestic MCI Patients

NCT04032626 | Completed Phase 2 DMC FDA Drug

• 3 other identifiers: 19-658R01AG059008K01AG047279
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

Accumulating evidence indicates that inflammation is prominent both in the blood and central nervous system (CNS) of Alzheimer's disease (AD) patients. These data suggest that systemic inflammation plays a crucial role in the cause and effects of AD neuropathology. Capitalizing on the experience from a previous clinical trial with thalidomide, here, the investigators hypothesize that modulating both systemic and CNS inflammation via the pleiotropic immunomodulator lenalidomide is a putative therapeutic intervention for AD if administered at a proper time window during the course of the disease.

Conditions

Cognitive Impairment, Mild; Cognitive Dysfunction; Amyloid Plaque; Neurodegeneration; Inflammation, Brain

Keywords

Alzheimer's disease; Biomarkers; Brain Amyloid; Brain Imaging; Cognition; Immunomodulation

Outcome Measures

Primary Outcomes (4)

• Change in cognition as assessed by the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) total score

  To evaluate the effect on cognition Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) of lenalidomide 10 mg/kg titrated for up to 12 months and washed out for 6 months. ADAS is 70 points. A lower score is better

  18 months

• Change in cognition as assessed by the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) total score

  To evaluate the effect on cognitionAlzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) of lenalidomide 10 mg/kg titrated for up to 12 months and washed out for 6 months. The maximum score is 30. A higher score is better

  18 months

• Change in cognition as assessed by the Clinical Dementia Rating - Sum of Boxes (CDR-SOB) total score

  To evaluate the effect on cognition Clinical Dementia Rating - Sum of Boxes (CDR-SOB) of lenalidomide 10 mg/kg titrated for up to 12 months and washed out for 6 months. The SOB maximum total is 18. A lower score is better

  18 months

• Change in cognition as assessed by the Mini Mental State Examination (MMSE) total score

  To evaluate the effect on cognition Mini Mental State Examination (MMSE) of lenalidomide 10 mg/kg titrated for up to 12 months and washed out for 6 months. The maximum score is 30. A higher score is better

  18 months

Secondary Outcomes (1)

• Monitoring and recording of all adverse events (AEs) and serious adverse events (SAEs)

  18 months

Other Outcomes (3)

• Change in brain amyloid loads

  18 months

• Change in neurodegeneration

  18 months

• Change in blood inflammatory markers

  18 months

Study Arms (2)

Lenalidomide

EXPERIMENTAL

Lenalidomide 10 mg/day taken daily orally for 12 months of treatment followed by 6 months washout. The trial will last 18 month in duration.

Drug: Lenalidomide 10 mg

Placebo

PLACEBO COMPARATOR

Placebo taken daily orally for 12 months of treatment followed by 6 months washout. The trial will last 18 month in duration.

Drug: Placebo

Interventions

Lenalidomide 10 mg DRUG

Lenalid

Also known as: Lenalid

Lenalidomide

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 50 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female outpatients.
• At least 50 years of age, but less than 90 (89 at time of screening).
• Females must be surgically sterile (bilateral tubal ligation, oophorectomy, or hysterectomy) or postmenopausal for 2 years (no women at risk of pregnancy will be accepted in this study).
• Must have been diagnosed with amnestic MCI based on the most recent NIA-AA criteria (Albert et al., 2011), i.e. at both the screening and baseline visits (visits 1 and 2) have a documented Mini Mental State Exam (MMSE) score between 22-28.
• CT or MRI scan of the brain obtained during the course of the dementia must be consistent with the diagnosis and show no evidence of significant focal lesions or of pathology which could contribute to dementia. If neither a CT nor an MRI scan is available from the past 12 months, a CT scan fulfilling the requirements must be obtained before randomization.
• Vision and hearing must be sufficient to comply with study procedures.
• Be able to take oral medications.
• Hachinski ischemic score must be ≤ 4.
• Geriatric depression scale must be ≤ 10.
• Can be on stable doses of a cholinesterase inhibitor and/or memantine as long as it is stable for at least 90 days before the Baseline (Week 00) and is expected to remain on a stable dose for the remainder of the study period; or have demonstrated intolerance to or lack of efficacy from these medications.
• Must have a collateral informant/study partner who has significant direct contact with the patient at least 10 hours per week and who is willing to accompany the patient to all clinic visits and to be present during all telephone visits/interviews.
• If the patient has a legally authorized representative (LAR), the LAR must review and sign the informed consent form. If the patient does not have an LAR, the patient must appear able to provide informed consent and must review and sign the informed consent form. In addition, the patient's informant/study partner (as defined above) must sign the informed consent form. If the LAR and the patient's informant /study partner is the same individual, he/she should sign under both designations.
• Must be able to attend all study visits indicated in the schedule of visits.
• Patients with stable prostate cancer may be included at the discretion of the Medical Monitor.
• Medical records must document evidence of amnestic MCI with 1 of the following: MRI with hippocampal volume in the 5th percentile or lower for age, Amyloid PET positive at SUVr ≥ 1.05, CSF Tau profile with ATI lower than 1.0, FDG PET showing hypometabolism in the parietal temporal regions, or genetic confirmation of APOE4 (heterozygous or homozygous).

You may not qualify if:

• Subjects will be excluded if they have any of the condition listed below:
• Current evidence or history within the last 3 years of a neurological or psychiatric illness that could contribute to dementia, including (but not limited to) epilepsy, focal brain lesion, Parkinson's disease, seizure disorder, head injury with loss of consciousness
• DSM IV criteria for any major psychiatric disorder including psychosis, major depression and bipolar disorder.
• Known history or self-reported alcohol or substance abuse.
• Isolated living circumstances which would prohibit a study partner from providing sufficient and credible information about the participant.
• Poorly controlled hypertension.
• History of myocardial infarction or signs or symptoms of unstable coronary artery disease within the last year (including revascularization procedure/angioplasty).
• Severe pulmonary disease (including chronic obstructive pulmonary disease) requiring more than 2 hospitalizations within the past year.
• Untreated sleep apnea.
• Any thyroid disease (unless euthyroid or on treatment for at least 6 months prior to screening).
• Active neoplastic disease (except for skin tumors other than melanoma). Patients with a history of prior malignancy are eligible provided they were treated with curative intent and (i) do not require any longer any active therapy; (ii) being considered in complete remission; and (iii) after the Medical Monitor's assessment/approval of each case.
• History of multiple myeloma.
• Absolute neutropenia of \<750mm3, or history of neutropenia.
• History of or current thromboembolism (including deep venous thrombosis).
• Any clinically significant hepatic or renal disease (including presence of Hepatitis B or C antigen/antibody or an elevated transaminase levels of greater than two times the upper limit of normal (ULN) or creatinine greater than 1.5 x ULN).

Sponsors & Collaborators

• St. Joseph's Hospital and Medical Center, Phoenix: lead
• National Institute on Aging (NIA): collaborator
• The Cleveland Clinic: collaborator

Study Sites (2)

St. Joseph&#39;s Hospital and Medical Center

Phoenix, Arizona, 85013, United States

Location

Cleveland Clinic Lou Ruvo Center for Brain health

Las Vegas, Nevada, 89103, United States

Location

MeSH Terms

Conditions

Cognitive Dysfunction; Plaque, Amyloid; Nerve Degeneration; Encephalitis; Alzheimer Disease

Interventions

Lenalidomide

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroinflammatory Diseases; Dementia; Tauopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Marwan N Sabbagh, M.D.

  St. Joseph's Hospital and Medical Center, Phoenix

  PRINCIPAL INVESTIGATOR

• Boris Decourt, PhD

  The Cleveland Clinic

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Beside the clinical pharmacologist and biostatistician, all parties involved in the present study will be blinded until all data are collected, including medical staff, patients and his/her car giver, imaging staff, and scientists collecting data from biosamples. The blinding will be lifted only after all data are acquired, and before statistical analysis.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology, Barrow Neurological Institute

Model Details: This study will take place at a single site. We will enroll 30 male and female outpatients, 50-90 years of age. Lenalidomide 10 mg/day vs. placebo will be taken daily orally (ratio 1:1). The effects of lenalidomide treatment will be assessed after 12 months of treatment and 6 months washout (month 18). Participants completing the study will be involved for up to 20 months in duration, from screening to end of study.

Study Record Dates

• First Submitted: July 10, 2019
• First Posted: July 25, 2019
• Study Start: July 22, 2020
• Primary Completion: May 31, 2025
• Study Completion: May 31, 2025
• Last Updated: June 13, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Published in a scientific paper (accessible online in 2020) Posters presented at scientific meetings (e.g. AAIC 2019)
• Access Criteria: * Papers will be accessible online * Data and biosamples can be requested from the principal investigator 6 months after publication of the results of the study in peer-reviewed articles

Locations

US (2)