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

Multiple Sclerosis, Relapsing-Remitting Clinical Trial

— ENSURE-2  

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-2)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05201638
• Other study ID #: P3-IMU-838-RMS-02
• Status: Recruiting
• Phase: Phase 3
• Start date: January 12, 2022
• Est. completion date: October 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-2)

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: 72 weeks (approximately 15 months) Open Label Extension Period: Up to approximately 8 years

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1050
• Est. completion date: October 2032
• Est. primary completion date: October 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 of COVID-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
• Multiple Sclerosis, Relapsing-Remitting
• 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
Armenia	Erebouni Medical Center	Yerevan
Armenia	Heratsi Hospital Complex 1	Yerevan
Bosnia and Herzegovina	UCC of Rep of Srpska	Banja Luka
Bosnia and Herzegovina	Cantonal Hospital Bihac Dr. Irfan Ljubijankic	Bihac
Bosnia and Herzegovina	University Clinical Center of Sarajevo	Sarajevo
Bosnia and Herzegovina	University Clinical Center Sarajevo	Sarajevo
Bosnia and Herzegovina	University Clinical Center Tuzla	Tuzla
Estonia	Astra Clinic	Tallinn
India	Post-Graduation Institute of Medical Education and Research (PGIMER)	Chandigarh
India	Fortis Memorial Research Institute	Gurugramam
India	Dr Ram Manohar Lohia Institute of Medical Sciences	Lucknow
India	All India Institute of Medical Sciences	New Delhi
India	GB Pant Institute of Postgraduate Medical Education and Research	New Delhi
India	SRI Guru Ram Das Institute of Medical Sciences and Research	Punjabi Bagh
India	DKS PGI	Raipur
Peru	Centro de Investig. Médicas	Lima
Poland	Neuro-Medic Janusz Zbrojkiewicz	Katowice
Poland	NZOZ Wielospecjalistyczna Poradnia Lekarska "Synapsis"	Katowice
Poland	Indywidualna Praktyka Lekarska prof. Konrad Rejdak	Lublin
Poland	NZOZ Neuromed	Lublin
Poland	Instytut Zdrowia Boczarska	Oswiecim
Poland	NZOZ Hertmanowskiej	Plewiska
Poland	NZOZ Neuro-Kard	Poznan
Poland	Centrum Medyczne NeuroProtect	Warsaw
Poland	FutureMeds Warszawa Centrum	Warsaw
Poland	Centrum Med. Ibismed	Zabrze
Romania	Elias University Emergency Hospital	Bucharest
Romania	SC Sana Monitoring SRL	Bucharest
Romania	Clubul Sanatatii SRL	Câmpulung
Romania	Spitalul clinic CF Constanta	Constanta
Romania	Asociatia Comunitatea Oamenilor	Craiova
Romania	Aria Clinic SRL	Sibiu
Romania	Neuro Therapy	Timisoara
Romania	Spit Jud Branzeu TIM Neuro	Timisoara
Serbia	Klinicko bolnicki centar Dr Dragisa Misovic - Dedinje	Belgrade
Serbia	Klinicko bolnicki centar Zvezdara	Belgrade
Serbia	Opsta bolnica Medicinski sistem Beograd	Belgrade
Serbia	Vojnomedicinska akademija	Belgrade
Serbia	Univerzitetski Klinicki centar Kragujevac	Kragujevac
Serbia	Univerzitetski Klinicki centar Kragujevac	Kragujevac
Serbia	Univerzitetski Klinicki centar Nis	Niš
Serbia	Hsptl Sveti Vracevi	Novi Kneževac
Serbia	General Hospital Uzice	Užice
Serbia	Klinicko Bolnicki centar Zemun	Zemun
Serbia	Opsta bolnica Djordje Jovanovic Zrenjanin	Zrenjanin
Turkey	Acibadem Adana Hospital	Adana
Turkey	Adana Baskent Hospital	Adana
Turkey	Baskent University Ankara Hospital	Ankara
Turkey	Bezmialem Vakif University Hospital	Istanbul
Turkey	Haydar Pasa Num. EAH	Istanbul
Turkey	Marmara University Pendik Training and Research Hospital	Istanbul
Turkey	Sancaktepe Sehit Prof.Dr. Ilhan Varank Training and Research Hospital	Istanbul
Turkey	T.C. Ministry of Health Istanbul Haseki Training and Research Hospital	Istanbul
Turkey	Kocaeli University Research and Application Hospital	Kocaeli
Turkey	T.C. Ministry of Health Kutahya Provincial Directorate of Health Kutahya University of Health Sciences Evliya Celebi Training and Research Hospital	Kütahya
Turkey	Manisa Celal Bayar University Hafsa Sultan Hospital	Manisa
Turkey	19 Mayis University Medical Faculty Hospital Health Application and Research Center	Samsun
Turkey	Namik Kemal Uni Hospital	Tekirdag
Turkey	Zonguldak Bulent Ecevit University Health Practice and Research Hospital	Zonguldak
Ukraine	Communal noncommercial enterprise "First Cherkasy City Hospital"	Cherkasy
Ukraine	MS Diagnosis Treatment Center	Cherkasy
Ukraine	Chernihiv City Hospital 4	Chernihiv
Ukraine	"University Clinic" of Dnipro State Medical University, Department of Neurology	Dnipro
Ukraine	Dnipro City Hospital 6	Dnipro
Ukraine	Municipal Institution "Dnipropetrovsk Regional Rehabilitation Hospital" of Dnipropetrovsk Regional Council"	Dnipro
Ukraine	Ukrainian State Research Institute of Medico-Social Problems of Disability	Dnipro
Ukraine	Communal Non-Commercial Medical Enterprise "O.T.Bohayevskyi Kremenchuk City Hospital #1	Kremenchuk
Ukraine	1 Private Clinic Medical Center	Kyiv
Ukraine	Dopomoga Plus medical center	Kyiv
Ukraine	State Institution "National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine	Kyiv
Ukraine	Volyn Reg Clin Hospital	Luts'k
Ukraine	5 City Clin Hospital	Lviv
Ukraine	Lviv Regional Central Hospital	Lviv
Ukraine	Communal institution "City Clinical Hospital ?3" of Poltava City Council	Poltava
Ukraine	City Clinical Hospital 2	Rivne
Ukraine	Sumy Reg Clinical Hospital	Sumy
Ukraine	Salutem	Vinnytsia
Ukraine	LCC Medical center INET-09	Zaporizhzhya
Ukraine	Zaporizhia Med	Zaporizhzhya
Ukraine	Zaporizhia Regional Clinic Hospital	Zaporizhzhya
Ukraine	Zaporizhzhya City Hospital 6	Zaporizhzhya
Ukraine	Zaporizhzhya Hospital 9	Zaporizhzhya
United Kingdom	Royal Devon Uni NHS	Exeter
United Kingdom	Royal Hallamshire Hospital	Sheffield
United States	Neuro of Central Florida	Altamonte Springs	Florida
United States	Boston Clinical Trials	Boston	Massachusetts
United States	Healthcare Innovations	Coral Springs	Florida
United States	Homestead Associates	Miami	Florida
United States	Premier Clinical Research	Miami	Florida
United States	Baptist Health Lexington	Nicholasville	Kentucky
United States	HonorHealth Research Institute - Bob Bove Neuroscience Institute	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Immunic AG

Countries where clinical trial is conducted

United States,  Armenia,  Bosnia and Herzegovina,  Estonia,  India,  Peru,  Poland,  Romania,  Serbia,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate efficacy of IMU-838 versus placebo based on 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 by assessment of occurrence of Adverse Events.	72 weeks