Study to Evaluate the Efficacy, Safety, and Tolerability of IMU-838 in Patients With Relapsing Multiple Sclerosis

Multiple Sclerosis Clinical Trial

— ENSURE-1  

Official title:

A Multi-Center, Randomized, Double-Blinded Phase 3 Study to Evaluate the Efficacy, Safety, and Tolerability of IMU-838 Versus Placebo in Adults With Relapsing Multiple Sclerosis (ENSURE-1)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05134441
• Other study ID #: P3-IMU-838-RMS-01
• Status: Recruiting
• Phase: Phase 3
• Start date: November 18, 2021
• Est. completion date: September 2032

Study information

• Verified date: April 2024
• Source: Immunic AG
• Contact: Andreas Muehler, MD
• Phone: +49 89 2080 477 00
• Email: info[@]imux.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Multi-Center, Randomized, Double-Blinded Phase 3 Study to Evaluate the Efficacy, Safety, and Tolerability of IMU-838 versus Placebo in Adults with Relapsing Multiple Sclerosis (ENSURE-1)

Description:

This study will be a multicenter, randomized, double-blind, placebo-controlled study with a blinded Main Treatment Period (MT) and an Open Label Period (OLE) to evaluate the efficacy, safety, and tolerability of IMU-838 in adult patients with RMS. The study will consist of the following periods:

Screening Period: Approximately 28 days Main Treatment Period: Up to 72 weeks (approximately 15 months) Open Label Extension Period: Up to approximately 8 years

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1050
• Est. completion date: September 2032
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Male or female patient (age =18 to =55 years).

• Patients with an established diagnosis of MS according to 2017 McDonald Criteria.

• Patients with RMS comprising of relapsing remitting MS (RRMS) and active secondary progressive MS, both defined according to Lublin criteria 1996 and 2014.

• Active disease as defined by Lublin 2014 evidenced prior to Screening by:

1. At least 2 relapses in the last 24 months before randomization, or

2. At least 1 relapse in the last 12 months before randomization, or

3. A positive Gd+ MRI scan (brain and/or spine) in the last 12 months prior to randomization.

• Willingness and ability to comply with the protocol.

• Written informed consent given prior to any study-related procedure.

Exclusion Criteria:

• Patients with non-active secondary progressive MS and primary progressive MS.

• Any disease other than MS that may better explain the signs and symptoms, including history of complete transverse myelitis.

• Clinical signs or presence of laboratory findings suggestive for neuromyelitis optica (NMO) spectrum disorders or myelin oligodendrocyte glycoprotein (MOG)-IgG-associated encephalomyelitis

• Any active and uncontrolled coexisting autoimmune disease, other than MS (except for type 1 diabetes mellitus and inflammatory bowel disease)

• Use of experimental/investigational drug (with the exception ofCOVID-19 vaccines approved by emergency use authorization) and/or participation in drug clinical studies within 6 months prior to Screening

• Previous or current use of MS treatments lifelong, or within a pre-specified time period.

• Use of the pre-specified concomitant medications.

• Clinically significantly abnormal and pre-specified lab values.

• History of chronic systemic infections within 6 months before the date of informed consent.

• Diagnosis or suspected liver function impairment, which may cause fluctuating liver function tests during this study.

• Known history of nephrolithiasis or underlying condition with a strong association of nephrolithiasis.

• History or clinical diagnosis of gout.

• History or presence of any major medical or psychiatric illness

• Substantial medical condition that could create undue risk to the patient, could affect adherence with the study protocol or could undesirably affect study outcomes

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• IMU-838 tablets
Patients are randomized to IMU-838 or placebo in ratio 1:1
• Placebo matching IMU-838 tablets
Patients are randomized to IMU-838 or placebo in ratio 1:1

Locations

Country	Name	City	State
Albania	Hygeia Hospital Tirana	Tirana
Albania	Klinika Mjekesore Nuova, Neurology Clinic	Tirana
Bulgaria	MHAT Puls AD	Blagoevgrad
Bulgaria	MHAT "Heart and Brain", EAD	Burgas
Bulgaria	Heart and Brain University Hospital	Pleven
Bulgaria	MC Exacta Medica OOD	Pleven
Bulgaria	MC Vita 1	Pleven
Bulgaria	MHAT Avis Medica	Pleven
Bulgaria	UMHAT Dr.Georgi Stranski EAD	Pleven
Bulgaria	UMHAT Sveti Georgi	Plovdiv
Bulgaria	UMHAT "Medica Ruse"	Ruse
Bulgaria	CCB Medical Institute Ministry of Interior	Sofia
Bulgaria	Diagnostic and Consultative Center Neoclinic	Sofia
Bulgaria	MHAT "Sveta Sofia" EOOD	Sofia
Bulgaria	MHATNP "Sveti Naum", EAD	Sofia
Bulgaria	MHATNPsy Sveti Naum EAD	Sofia
Bulgaria	Military Medical Academy	Sofia
Bulgaria	Military Medical Academy MHAT	Sofia
Bulgaria	UMHAT "Alexandrovska"	Sofia
Bulgaria	UMHAT "Alexandrovska" EAD	Sofia
Bulgaria	UMHAT "Sveti Ivan Rilski" EAD	Sofia
Bulgaria	UMHAT"Tsaritsa Yoanna -ISUL	Sofia
Bulgaria	UMHATEM N.Pirogov	Sofia
Bulgaria	UMHAT "Sveta Marina" EAD, First Clinic of Neurological Diseases	Varna
Colombia	Clínica Colsanitas S.A. Sede Clínica Universitaria Colombia	Bogotá
Colombia	Neurocountry Portoazul S.A.S.	Puerto Colombia
Georgia	1st Uni Clinic of Tbilisi LEPL	Tbilisi
Georgia	Eristavi Experimental Center	Tbilisi
Georgia	J.S.C. Curatio Clinic	Tbilisi
Georgia	Katsiashvili Emergency Center	Tbilisi
Georgia	Khechinashvili University Hospital	Tbilisi
Georgia	LTD Aversi Clinic	Tbilisi
Georgia	LTD New Hospitals	Tbilisi
Georgia	MediClub Georgia LLC	Tbilisi
Georgia	Pineo Medical Ecosystem LTD	Tbilisi
Georgia	Sarajishvili Neurology Institute	Tbilisi
Greece	Athens Medical Center	Athens
Greece	Thessaloniki Hosptl	Thessaloníki
India	Kanoria Hospital & Research Centre	Gandhinagar
India	Mallikatte, Kadri	Mangalore
India	Jasleen Hospital	Nagpur
India	Sir Ganga Ram Hospital	New Delhi
India	Ruby Hospital	Pune
India	Indira Gandhi Medical College & Hospital	Shimla
India	Institute of Medical Sciences Banaras Hindu University,IMS BHU Varanasi	Varanasi
Jordan	TSH Advanced Clinical Center	Amman
Jordan	Irbid Speciality Hospital	Irbid
Lebanon	Hotel Dieu de France Hospital	Beirut
Lebanon	AUB Medical Center	Hamra
Lithuania	Lietuvos Sveikatos Mokslu Universitetas - Kauno Klinikos	Kaunas
Lithuania	Klaipedos Universitetine Ligonine - Klaipedos Issetines Sklerozes Centra	Klaipeda
Mexico	Neurociencias Estudios Clínicos S.C	Culiacán
Mexico	Instituto Jalisciense de Metabolismo, SC	Guadalajara
Mexico	Cliditer S.A de C.V	Mexico City
Mexico	Clinstile SA de CV	Mexico City
Mexico	Grupo medico camino SC	Mexico City
Mexico	Unidad de Investigación en Salud de Chihuahua S.C.	Mexico City
Mexico	Centro de Morelia	Morelia
Mexico	Faicic de RL de CV	Veracruz
Mexico	Sociedad de Metabolismo y Corazon, S.C.	Veracruz
Moldova, Republic of	Instititute of Emergency Medicine	Chisinau
Moldova, Republic of	Medico-Sanitary Public Institution, Institute of Neurology and Neurosurgery "Diomid Gherman"	Chisinau
Moldova, Republic of	The Diomid Gherman Institute of Neurology and Neurosurgery	Chisinau
Montenegro	General Hospital Niksic	Nikšic
Montenegro	Clinical Center of Montenegro	Podgorica
North Macedonia	Hospital "8 mi Septemvri"	Skopje
North Macedonia	University Clinic of Neurology	Skopje
Spain	Hospital Universitario La Paz	Madrid
Ukraine	Chernihiv Regional Hospital	Chernivtsi
Ukraine	Neuro Global, LLC	Ivano-Frankivs'k
Ukraine	Regional Clinical Hospital	Ivano-Frankivs'k
Ukraine	Khmelnytsky regional hospital of war veterans	Khmelnytskyi
Ukraine	Clinical Hospital #15 of the Podilskyi District of the Kyiv City	Kiev
Ukraine	Kyiv City Hospital 4	Kiew
Ukraine	"Medbud"	Kyiv
Ukraine	SMART medical center	Kyiv
Ukraine	Odesa Regional Clinical Hospital, Department of Neurosurgery	Odesa
Ukraine	Medical and diagnostic center of a LLC "Medcontinent", neurology and rehabilitation center	Poltava
Ukraine	Ternopil Psycho-Neuro Hospital	Ternopil'
Ukraine	Regional Clinical Center for Neurosurgery and Neurology	Uzhhorod
United States	Bradenton Research Center	Bradenton	Florida
United States	Reliant Medical Research, LLC	Miami	Florida
United States	Collier Neurologic Specialists	Naples	Florida
United States	Consultants in Neurology, Ltd	Northbrook	Illinois
United States	Neurology Associates of Ormond Beach	Ormond Beach	Florida
United States	Xenoscience, Inc., 21st Century Neurology	Phoenix	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Immunic AG

Countries where clinical trial is conducted

United States,  Albania,  Bulgaria,  Colombia,  Georgia,  Greece,  India,  Jordan,  Lebanon,  Lithuania,  Mexico,  Moldova, Republic of,  Montenegro,  North Macedonia,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate efficacy of IMU-838 versus placebo regarding time to first relapse	Survival analysis of time to first relapse, occurred after the start of study treatment administration and before the end of the double-blind period, censored at a maximum of 72 weeks.	72 weeks
Secondary	Effect of IMU-838 versus placebo on volume of new T2 lesions	To evaluate the effect of IMU-838 versus placebo on volume of new T2 lesions. Mean difference between IMU-838- and placebo in changes of the volume of new MRI T2 lesions over 24-weeks of treatment in the double-blind period.	72 weeks
Secondary	Effect of IMU-838 versus placebo on disability progression	To evaluate the effect of IMU-838 versus placebo on disability progression. Survival analysis of time to 12-week confirmed disability progression, as measured on Expanded Disability Status Scale during the double-blind period, censored at maximum 72-weeks.	72 weeks
Secondary	Effect of IMU-838 versus placebo on cognitive performance	To evaluate the effect of IMU-838 versus placebo on cognitive performance. Survival analysis of time to confirmed clinically relevant changes on Symbol Digit Modalities Test during the double-blind period, censored at maximum 72-weeks.	72 weeks
Secondary	Effect of IMU-838 versus placebo on whole brain atrophy	To evaluate the effect of IMU-838 versus placebo on whole brain atrophy. Difference in the mean of the percentage change on the whole brain volume between IMU-838 and placebo during the 72-weeks double-blind period.	72 weeks
Secondary	Safety of IMU-838 versus placebo	To evaluate safety and tolerability of IMU-838 versus placebo by assessing rates of Treatment Emergent Adverse Events, Adverse Events of Special Interest, Serious Adverse Events, changes in levels of pre-specified laboratory parameters, vital signs and ECG parameters and rates and reasons for study discontinuations.	72 weeks