A Phase-2b, Double-Blind, Randomized Controlled Trial to Evaluate the Activity and Safety of Inebilizumab in Anti-Nmda Receptor Encephalitis and Assess Markers of Disease

Status: Recruiting
Location: See all (39) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 2
SUMMARY

Determine the difference in the modified Rankin score at 16 weeks in participants with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis treated with first-line immunomodulatory therapies provided as standard-of-care, and either inebilizumab (investigational agent) or placebo.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 12
Healthy Volunteers: f
View:

• Diagnosis of NMDAR encephalitis, defined by both a and b:

‣ A subacute onset of change in mental status consistent with autoimmune encephalitis,

⁃ A positive cell-based assay for anti-NMDA receptor IgG antibody in the CSF confirmed in study-specified laboratories.

• Participants, ≥ 12 years of age at the time of informed consent. Participants under 18 years of age must weigh ≥40 kilograms.

• Written informed consent and any locally required authorization (e.g., Health Insurance Portability and Accountability Act \[HIPAA\] in the United States of America \[USA\], European Union \[EU\] Data Privacy Directive in the EU) obtained from the participant/legal representative prior to performing any protocol-related procedures, including screening evaluations.

• Non-sterilized participants who are sexually active with a partner capable of becoming pregnant must use a condom with spermicide from Day 1 through to the end of the study and must agree to continue using such precautions for at least 6 months after the final dose of IP. A recommendation will be made that the partners (capable of becoming pregnant) of study participants (capable of getting their partner pregnant) should use a highly effective method of contraception other than a physical method.

• Participants of childbearing potential who are sexually active with a non-sterilized partner capable of getting their partner pregnant must agree to use a highly effective method of contraception beginning at screening or upon discharge from hospitalization/inpatient rehabilitation (for participants who were incapacitated at the time of screening), and to continue precautions for 12 months after the final dose of IP.

⁃ Participants of childbearing potential are defined as those who are not surgically sterile (e.g., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or those who are not postmenopausal (per ICH M3 (R2) 11.2: defined as 12 months with no menses without an alternative medical cause).

⁃ A highly effective method of contraception is defined as one that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly. Periodic abstinence, the rhythm method, and the withdrawal method do not qualify as highly effective or acceptable methods of contraception for study purposes. Acceptable methods of contraception are listed in the table below:

‣ Physical Methods Hormonal Methods e

‣ • Intrauterine device (IUD)

‣ • Intrauterine hormone-releasing system, also known as drug-eluting IUD a

‣ • Bilateral tubal occlusion

‣ • Vasectomized partner b

‣ • Sexual abstinence c • Combined (estrogen and progestogen-containing hormonal contraception)

∙ Oral (combined pill)

∙ Injectable

∙ Transdermal (patch)

∙ Progestogen-only hormonal contraception associated with inhibition of ovulation d

∙ Implantable

∙ Intravaginal a This is also considered to be a hormonal method. b With appropriate post-vasectomy documentation of surgical success (absence of sperm in ejaculate).

‣ c Sexual abstinence is considered to be a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of the study and if it is the preferred and usual lifestyle of the participant.

‣ d Progestogen-only hormonal contraception, where inhibition of ovulation is not the primary mode of action (minipill) is not accepted as a highly effective method.

‣ e These methods are only considered highly effective and therefore acceptable when used in conjunction with a barrier method (i.e., diaphragm with spermicide, sponge with spermicide, cervical cap with spermicide, condoms, spermicide alone.)

• Willing to forgo other immunomodulatory therapies (investigational or otherwise) for NMDAR encephalitis during the study.

• Participant must have received at least 3 days of methylprednisolone 1000 mg IV or equivalent corticosteroid within 90 days prior to randomization (Day 1). In addition, participants must have received EITHER of the following treatments within 90 days before randomization.

‣ IVIg, at a dose range between 1.2 and 2 g/kg

⁃ Plasma exchange or plasmapheresis, (defined as 5 to 6 exchanges).

• NOTE: These treatments may be provided during the screening period but must be completed prior to randomization. Participants who receive methylprednisolone and BOTH IVIg and plasma exchange are not excluded from participating in the trial, however, this treatment course with both IVIg and plasma exchange is not encouraged, and enrollment and randomization should not be delayed in order to complete additional first line treatments.

• Modified Rankin Score of ≥3 at the screening visit, indicating at least moderate disability. The baseline mRS must be confirmed by Site Investigators at screening and confirmed / adjudicated before randomization.

• Ability and willingness to attend study visits and complete the study. \*All inclusion criteria must be met during the screening period, prior to randomization, except where noted.

Locations
United States
Alabama
University of Alabama at Birmingham
RECRUITING
Birmingham
Arizona
St. Joseph Hospital and Medical Center Barrow Neurological Institute
RECRUITING
Phoenix
Mayo Clinic in Arizona
RECRUITING
Scottsdale
California
Children's Hospital of Orange County
RECRUITING
Orange
UC Irvine
RECRUITING
Orange
UC Davis
RECRUITING
Sacramento
Colorado
Children's Hospital Colorado Main Campus
RECRUITING
Aurora
University of Colorado
RECRUITING
Aurora
Connecticut
Yale University
RECRUITING
New Haven
Florida
Mayo Clinic Jacksonville
RECRUITING
Jacksonville
University of Miami
RECRUITING
Miami
Georgia
Emory University
RECRUITING
Atlanta
Iowa
University of Iowa
RECRUITING
Iowa City
Illinois
Ann and Robert H. Lurie Childrens Hospital of Chicago
RECRUITING
Chicago
Northwestern University Feinberg School of Medicine
RECRUITING
Chicago
Massachusetts
Massachusetts General Hospital
RECRUITING
Boston
Michigan
University of Michigan Health System
RECRUITING
Ann Arbor
Minnesota
Mayo Clinic Rochester
RECRUITING
Rochester
Missouri
Washington University in St. Louis School of Medicine
RECRUITING
St Louis
North Carolina
Wake Forest University Health Sciences
RECRUITING
Winston-salem
New York
SUNY Downstate
RECRUITING
Brooklyn
Columbia University Medical Center
RECRUITING
New York
Mount Sinai
RECRUITING
New York
University of Rochester
RECRUITING
Rochester
SUNY Buffalo
RECRUITING
Williamsville
Ohio
University of Cincinnati
RECRUITING
Cincinnati
Ohio State University
RECRUITING
Columbus
Pennsylvania
University of Pennsylvania
RECRUITING
Philadelphia
University of Pittsburgh
RECRUITING
Pittsburgh
Tennessee
Vanderbilt University
RECRUITING
Nashville
Texas
University of Texas Southwestern Medical Center
RECRUITING
Dallas
Texas Children's Hospital
RECRUITING
Houston
Utah
University of Utah
RECRUITING
Salt Lake City
Virginia
University of Virginia
RECRUITING
Charlottesville
Washington
University of Washington
RECRUITING
Seattle
Other Locations
Netherlands
Erasmus Medical University Center
RECRUITING
Rotterdam
Erasmus University Rotterdam
RECRUITING
Rotterdam
Spain
Hospital Clínic Barcelona
RECRUITING
Barcelona
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona
RECRUITING
Barcelona
Contact Information
Primary
Stacey L Clardy, MD, PhD
stacey.clardy@hsc.utah.edu
8015857575
Backup
Ka-Ho Wong, MBA
ka-ho.wong@hsc.utah.edu
8015857575
Time Frame
Start Date: 2022-03-30
Estimated Completion Date: 2028-09-30
Participants
Target number of participants: 116
Treatments
Active_comparator: Inebilizumab
Approximately 58 patients will receive Inebilizumab in addition to first line immunotherapy.~(Approximately 116 participants will be randomized in a 1:1 ratio to 2 treatment groups; approximately 58 participants to each treatment group).~All participants will also receive a 3 day course of IVIg.
Placebo_comparator: Placebo
Approximately 58 patients will receive placebo in addition to first line immunotherapy.~(Approximately 116 participants will be randomized in a 1:1 ratio to 2 treatment groups; approximately 58 participants to each treatment group).~All participants will also receive a 3 day course of IVIg.
Sponsors
Leads: University of Utah

This content was sourced from clinicaltrials.gov