An Exploratory Study of the Potential for Rational Immune System Manipulation to Prevent Emergence of Synucleinopathy Manifestations in Persons With REM Sleep Behavior Disorder (RBD)

NCT06996652 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 20000384762000038206YPD-001
• Study Type: interventional
• Target: 108
• Locations: 2 countries
• Sites: 20

Brief Summary

This is a phase 2 study to assess the ability of adalimumab as compared to placebo to reduce or prevent progression of synuclein-related neurodegeneration in persons with idiopathic REM Sleep Behavior Disorder (RBD). The Primary Endpoint will be change from baseline in expression of the Parkinson Disease Related Pattern (PDRP) will be assessed using change in 18-flurodeoxyglucose (FDG) Positron Emission Tomography (PET) imaging.

Conditions

REM Sleep Behavior Disorder

Keywords

Parkinson Disease Related Pattern

Outcome Measures

Primary Outcomes (1)

• Change in Parkinson Disease Related Pattern (PDRP) expression

  Change from Baseline to Week 96in the expression of the Parkinson Disease Related Pattern (PDRP) assessed by 18-flurodeoxyglucose (FDG) Positron Emission Tomography (PET).

  Baseline and Week 96

Secondary Outcomes (6)

• Percentage of participants that experience adverse events

  up to Week 96

• Percentage of participants with clinical laboratory abnormalities

  up to Week 96

• Percentage of participants with possible new onset of disease

  up to Week 96

• Percentage of participants with new onset of disease

  up to Week 96

• Percentage of participants with serum anti-adalimumab antibodies (ADAs)

  up to Week 96

Study Arms (2)

Adalimumab

EXPERIMENTAL

Participants in this arm will receive Adalimumab every 2 weeks for up to 2 years

Drug: Adalimumab

Placebo

PLACEBO COMPARATOR

Participants in this arm will receive matching placebo every 2 weeks for up to 2 years

Drug: Placebo

Interventions

Adalimumab DRUG

40 mg self-administered subcutaneously using a pre-filled syringe (PFS) every 2 weeks for up to 2 years

Adalimumab

Placebo DRUG

40 mg matching placebo self-administered subcutaneously using a pre-filled syringe (PFS) every 2 weeks for up to 2 years

Placebo

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males, or females who are either
• post-menopausal or otherwise not of child-bearing potential, defined as either 1) having had no menses for 12 or months without an alternative medical cause or explanation or 2) having undergone a surgical procedure (hysterectomy, bilateral tubal ligation) that prevents conception, or
• practicing adequate contraception. Female subjects of childbearing potential must practice at least 1 protocol-specified method of birth control, that is effective from 30 days before baseline (or earlier) through at least 150 days after the last dose of the study drug. Female subjects of non-childbearing potential do not need to use birth control.
• Diagnosis of idiopathic REM sleep behavior disorder Diagnosis of idiopathic REM Sleep Behavior Disorder (RBD) based upon:
• History of Dream Enactment Behavior during sleep and
• Evidence of REM sleep without muscle atonia based upon polysomnogram obtained in a qualified sleep laboratory, consistent with ICSD-3 Diagnostic Criteria for RBD
• Hyposmia, defined as score \< 15th percentile for age-and gender-specific normal values
• Not diagnosed with motor parkinsonism or Lewy body dementia
• Have a MoCA score at screening and baseline \>23
• Able to speak, read and write fluently in English, Spanish, or French
• Subject must be willing and able to attend all study visits as required by the study protocol
• Subject must have a study partner who is in regular contact with the subject and can accompany the subject to clinic visits and report on subject's functional status
• Subject must be able to self-inject study drug regularly or have a study partner who is available, willing and able to do so
• Subject must be able to understand the study requirements and provide written informed consent

You may not qualify if:

• Alternative explanation or etiology for the presence of RBD (e.g. narcolepsy)
• Other than RBD, neurologic or medical disorder which may impair cognition including: head trauma, seizure disorder, neurodegenerative disease, hydrocephalus, cerebral/spinal hematoma, inflammatory disease, CNS infection (e.g., encephalitis or meningitis), neoplasm, toxic exposure, metabolic disorder (including hypoxic or hypoglycemic episodes), or endocrine disorder, or any significant medical conditions that, in the opinion of the investigator, would prohibit their participation in the study.
• As assessed by the central reader, MRI evidence of (a) more than three lacunar infarcts, (b) territorial infarct or macroscopic hemorrhage, or (c) deep white matter lesions corresponding to a Fazekas score of 3
• Any contra-indication to undergo MRI, as judged by local PI or radiologist, including but not limited to presence of pacemaker, aneurysm clips, artificial heart valves, ear implants, ventriculoperitoneal shunt, foreign metal objects in the eyes, skin or body or any other circumstance which would contra-indicate an MRI scan or impair MRI image quality, or history of claustrophobia or of not tolerating MRI scanning procedures
• History or active presence of any of the following neurological, psychiatric or medical conditions:
• Large vessel stroke
• Peripheral or CNS demyelinating disease
• Chronic and/or recurrent fungal, bacterial or opportunistic infections
• Myocardial infarction or unstable angina within the previous 12 months
• Clinically relevant or significant ECG abnormalities, including ECG with QT interval corrected for heart rate using Fridericia's formula (QT interval corrected for heart rate using Fridericia's formula) \> 450 msec (males) or \> 470 msec (females).
• Congestive heart failure, NYHA Class 3 or 4
• Autoimmune disease (e.g., Systemic Lupus Erythematosis (SLE), or symptoms suggestive of a lupus-like syndrome, multiple sclerosis, rheumatoid arthritis, Type 1 diabetes mellitus, inflammatory bowel disease, psoriasis, etc.)
• Immunocompromised systemically due to continuing effects of immune suppressing medication
• Current or previous hepatitis B infection (defined as positive test for hepatitis B surface antigen (HbSAg) and/or hepatitis B core antibody (anti-HBc).
• Subjects with immunity to hepatitis B (if due to natural infection defined as negative HBsAg, positive hepatitis B antibody (anti-HBs) and positive anti-HBc; if due to vaccination defined as negative HBsAg, negative anti-HBc and positive anti-HBs are eligible to participate in the study For patients with resolved HBV infection, if anti-HBc negative, HBV DNA testing is needed prior to initiating study drug

Sponsors & Collaborators

• Yale University: lead
• The Marcus Foundation: collaborator
• National Institute on Aging (NIA): collaborator

Study Sites (20)

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

University of Colorado Anschutz

Aurora, Colorado, 80045, United States

Location

Yale Medicine

North Haven, Connecticut, 06473, United States

Location

Parkinson's Disease & Movement Disorders Center of Boca Raton

Boca Raton, Florida, 33486, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30329, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55414, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Cleveland Clinic Lou Ruvo Center for Brain Health - Las Vegas

Las Vegas, Nevada, 89106, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Weill Medical College of Cornell University

New York, New York, 10021, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19107, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29403, United States

Location

University of Texas Houston Medical Center

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center- San Antonio

San Antonio, Texas, 78229, United States

Location

Montreal Neurological Institute-Hospital at McGill University

Montreal, Quebec, H3A 2B4, Canada

Location

MeSH Terms

Conditions

REM Sleep Behavior Disorder

Interventions

Adalimumab

Condition Hierarchy (Ancestors)

REM Sleep Parasomnias; Parasomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jesse Cedarbaum, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Erika Renkl, BA

CONTACT

475-254-9169; erika.renkl@yale.edu

Kathy Gerich

CONTACT

katherine_gerich@URMC.rochester.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study sponsor and the investigational team will remain masked. An un-masked statistician and pharmacovigilance team will monitor safety of the study participants
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology

Model Details: Participants with REM sleep behavior disorder (RBD) who are at risk for developing motor and/or cognitive symptoms of Parkinson's disease or Lewy Body Dementia at up to 15 sites in the United States and Canada

Study Record Dates

• First Submitted: May 21, 2025
• First Posted: May 30, 2025
• Study Start: May 1, 2026
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): August 1, 2029
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: 2 years after completion of the trial and after publication of the primary study manuscript
• Access Criteria: Researchers who provide a methodologically sound proposal

Locations

US (19); CA (1)