Phase 2 Extension Trial in Patients With Relapsing-Remitting Multiple Sclerosis (RRMS)

NCT01226745 | Terminated Phase 2 Results DMC

• 2 other identifiers: ONO-4641POU007 (EMR200559-002)2010-018705-11
• Study Type: interventional
• Target: 340
• Locations: 11 countries
• Sites: 70

Brief Summary

The objective of this active-drug Extension Study is to evaluate the continuing safety and efficacy of ONO-4641 (MSC2430913A) in subjects with relapsing-remitting multiple sclerosis (RRMS) who have completed an initial 26-week Core Study (ONO-4641POU006 \[NCT01081782\]).

Conditions

Multiple Sclerosis

Keywords

Multiple sclerosis; ONO-4641; MSC2430913A; Efficacy

Outcome Measures

Primary Outcomes (8)

• Number of Subjects With Clinically Significant Abnormal Vital Signs

  Vital signs included oral temperature, pulse, respiration rate and blood pressure (BP) (taken after 5 minutes in the sitting position). The abnormalities in vital signs were decided as clinically significant or not based on the clinical judgment of the investigator.

  Baseline up to Week 255

• Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)

  FEV1 was defined as the maximal volume of air exhaled in the 1st second of a forced expiration from a position of full inspiration. FEV1 was obtained from spirometry, performed before study treatment administration. Early termination visit was recorded when the subject was early terminated from the study during the first 2.5 year period, while early termination 2 visit was recorded when the subject early terminated from the study during the additional 2 year period with delay shall be defined.

  Baseline, Week 40, 52, 76, 100, 124, 148, early termination, Week 152, 200, early termination 2, Week 255

• Change From Baseline in Forced Vital Capacity (FVC)

  FVC (% of predicted value) was the volume of air which was forcibly exhaled from the lungs after taking the deepest breath possible. Early termination visit was recorded when the subject was early terminated from the study during the first 2.5 year period, while early termination 2 visit was recorded when the subject early terminated from the study during the additional 2 year period with delay shall be defined.

  Baseline, Week 40, 52, 76, 100, 124, 148, early termination, Week 152, 200, early termination 2, Week 255

• Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)

  DLCO was one of the most clinically valuable tests of lung function. The DLCO measure the ability of the lungs to transfer gas from inhaled air to the red blood cells in pulmonary capillaries. Early termination visit was recorded when the subject was early terminated from the study during the first 2.5 year period, while early termination 2 visit was recorded when the subject was early terminated from the study during the additional 2 year period with delay. The values for the DLCO "% of predicted" was defined as the mean value of 2 test results that were within a 10% variability of each other.

  Baseline, Week 40, 52, early termination, Week 152, 200, 255

• Number of Subjects With Clinically Significant Abnormal Electrocardiogram (ECG) Measures

  The 12-lead ECG was recorded after the subject was in supine position for 5 minutes. ECGs were acquired on digital cardiographs. Abnormal findings were analyzed as clinically significant or not clinically significant as per the discretion of the study investigator.

  Baseline up to Week 255

• Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination

  Subjects underwent comprehensive ophthalmic examination (COE) including best corrected visual acuity (Snellen), manifest refractions, pupil examination, ocular motility, nystagmus, confrontation visual fields, Ishihara color plates, Amsler grid, and tonometry as well as a biomicroscopy slit lamp examination of the conjunctiva, cornea, anterior chamber, iris and lens; and a fundoscopic examination (with dilation) of the vitreous, optic nerve, retinal vessels, macula, and peripheral retina. Optical Coherence Tomography (OCT): Thicknesses of the macular retina and retinal nerve fiber layer at the optic nerve head in each eye was assessed by OCT using the fast macular thickness map scan and the fast retinal nerve fiber layer (RNFL) scan features, respectively. The abnormalities of the ophthalmologic examination was judged to be clinically significant or not as per the investigators discretion. The ophthalmologic examination was performed for both right eye (RE) and left eye (LE).

  Baseline up to Week 255

• Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination

  A whole body examination, paying particular attention to identify precancerous or cancerous lesions was done by a dermatologist and based on the clinical judgment of the dermatologist the abnormalities were categorized as clinically significant or clinically not significant. Early termination visit was recorded when the subject was early terminated from the study during the first 2.5 year period, while early termination 2 visit was recorded when the subject early terminated from the study during the additional 2 year period with delay shall be defined.

  Baseline up to end of the treatment, assessed up to Week 255

• Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation

  An Adverse Event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A Serious Adverse Event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs were defined as the AEs that occur between first dose of study drug administration and 35 days after the last dose of study drug administration that were absent before treatment or that worsened relative to pretreatment state.

  From the first dose of study drug administration up to 35 days after the last dose of study drug administration, assessed up to 5 years

Secondary Outcomes (3)

• Number of Gadolinium (Gd)-Enhanced Lesions

  Baseline, Week 40, 52, 100, 148, early termination, Week 152, 200, early termination 2, Week 255 and end of treatment (5 years)

• Change From Baseline in Lesion Volume at the End of the Treatment (EoT)

  Baseline, End of treatment (5 years)

• Percent Brain Volume Change (PBVC) From Baseline at the End of Treatment

  Baseline and at end of treatment (Week 255)

Study Arms (6)

ONO-4641 0.15 milligram (mg) - 0.15 mg

EXPERIMENTAL

Drug: ONO-4641

ONO-4641 0.10 mg - 0.10 mg

EXPERIMENTAL

Drug: ONO-4641

ONO-4641 0.05 mg - 0.05 mg

EXPERIMENTAL

Drug: ONO-4641

Placebo - ONO4641 0.15 mg

EXPERIMENTAL

Drug: ONO-4641

Placebo - ONO4641 0.10 mg

EXPERIMENTAL

Drug: ONO-4641

Placebo - ONO4641 0.05 mg

EXPERIMENTAL

Drug: ONO-4641

Interventions

ONO-4641 DRUG

Subjects will be administered with ONO-4641 at a dose of 0.15 milligram (mg) in the core study will be administered with ONO-4641 0.15 mg in this extension study for a duration of 225 weeks.

Also known as: MSC2430913A, Ceralifimod

ONO-4641 0.15 milligram (mg) - 0.15 mg

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Completed 26 weeks of double-blind phase of Study ONO-4641POU006

You may not qualify if:

• Presence of any dermatological abnormalities during Study ONO-4641POU006 that could increase the risk of the patient developing a skin cancer

Sponsors & Collaborators

• EMD Serono: lead
• Merck KGaA, Darmstadt, Germany: collaborator
• Ono Pharmaceutical Co. Ltd: collaborator

Study Sites (70)

Tucson Clinical Site 133

Tucson, Arizona, 85705, United States

Location

Aurora Clinical Site 132

Aurora, Colorado, 80045, United States

Location

Fort Collins Clinical Site 123

Fort Collins, Colorado, 80528, United States

Location

Fairfield Clinical Site 110

Fairfield, Connecticut, 06824, United States

Location

Ormond Beach Clinical Site 129

Ormond Beach, Florida, 32174, United States

Location

Sarasota Clinical Site 116

Sarasota, Florida, 34243, United States

Location

Northbrook Clinical Site 135

Northbrook, Illinois, 60062, United States

Location

Fort Wayne Clinical Site 111

Fort Wayne, Indiana, 46805, United States

Location

Indianapolis Clinical Site 121

Indianapolis, Indiana, 46202, United States

Location

Detroit Clinical Site 104

Detroit, Michigan, 48202, United States

Location

Farmington Hills Clinical Site 126

Farmington Hills, Michigan, 48334, United States

Location

Lebanon Clinical Site 115

Lebanon, New Hampshire, 03756, United States

Location

Albuquerque Clinical Site 106

Albuquerque, New Mexico, 87131, United States

Location

Rochester Clinical Site 108

Rochester, New York, 14642, United States

Location

Charlotte Clinical Site 125

Charlotte, North Carolina, 28201, United States

Location

Raleigh Clinical Site 103

Raleigh, North Carolina, 27607, United States

Location

Akron Clinical Site 112

Akron, Ohio, 44320, United States

Location

Philadelphia Clinical Site 120

Philadelphia, Pennsylvania, 19104, United States

Location

Knoxville Clinical Site 134

Knoxville, Tennessee, 37934, United States

Location

Round Rock Clinical Site 107

Round Rock, Texas, 78681, United States

Location

Brugge Clinical Site 203

Bruges, 8000, Belgium

Location

La Louviere Clinical Site 201

La Louvière, 8000, Belgium

Location

Vancouver Clinical Site 131

Vancouver, British Columbia, V6T 2B5, Canada

Location

Gatineau Clinical Site 114

Gatineau, Quebec, Canada

Location

Greenfield park Clinical Site 109

Greenfield Park, Quebec, J4V2J2, Canada

Location

Montreal Clinical Site 101

Montreal, Quebec, H1T2M4, Canada

Location

Montreal Clinical Site 102

Montreal, H9X3Z9, Canada

Location

Olomouc Clinical Site 212

Olomouc, 775 20, Czechia

Location

Pardubice Clinical Site 211

Pardubice, 53203, Czechia

Location

Praha 5 Clinical Site 213

Prague, 15006, Czechia

Location

Glessen Clinical Site 221

Glessen, 35385, Germany

Location

Leipzig Clinical Site 229

Leipzig, 04103, Germany

Location

Marburg Clinical Site 228

Marburg, 35033, Germany

Location

Tubingen Clinical Site 226

Tübingen, 72076, Germany

Location

Athens Clinical Site 243

Athens, 115 29, Greece

Location

Kanto Region Clinical Site 404

Kanto, Japan

Location

Kanto Region Clinical Site 405

Kanto, Japan

Location

Kanto Region Clinical Site 406

Kanto, Japan

Location

Kanto Region Clinical Site 409

Kanto, Japan

Location

Kinki Region Clinical Site 401

Kinki, Japan

Location

Kinki Region Clinical Site 407

Kinki, Japan

Location

Kinki Region Clinical Site 408

Kinki, Japan

Location

Tohoku Region Clinical Site 403

Tōhoku, Japan

Location

Tohoku Region Clinical Site 410

Tōhoku, Japan

Location

Bialystok Clinical Site 305

Bialystok, 15-402, Poland

Location

Czeladz Clinical Site 303

Czeladź, 41-250, Poland

Location

Gdansk Clinical Site 302

Gdansk, 80-803, Poland

Location

Katowice Clinical Site 309

Katowice, 40-594, Poland

Location

Krakow Clinical Site 307

Krakow, 31-530, Poland

Location

Lodz Clinical Site 306

Lodz, 90-153, Poland

Location

Plewiska Clinical Site 304

Plewiska, 62-064, Poland

Location

Warszawa Clinical Site 308

Warsaw, 04-749, Poland

Location

Kazan Clinical Site 333

Kazan', 420103, Russia

Location

Moscow Clinical Site 332

Moscow, 107150, Russia

Location

Moscow Clinical Site 330

Moscow, 121356, Russia

Location

Nizhniy Novgorod Clinical Site 321

Nizhny Novgorod, 107150, Russia

Location

Novosibirsk Clinical Site 324

Novosibirsk, 630091, Russia

Location

St. Petersburg Clinical Site 325

Saint Petersburg, 194354, Russia

Location

Samara Clinical Site 329

Samara, 443095, Russia

Location

Ufa Clinical Site 326

Ufa, 450005, Russia

Location

Barcelona Clinical Site 252

Barcelona, 08025, Spain

Location

Barcelona Clinical Site 253

Barcelona, 08025, Spain

Location

Bilbao Clinical Site 255

Bilbao, 48013, Spain

Location

Girona Clinical Site 254

Girona, 17007, Spain

Location

Hospitalet de Llobregat Clinical Site 251

L'Hospitalet de Llobregat, 08907, Spain

Location

Sevilla Clinical Site 256

Seville, 41071, Spain

Location

Dnipropetrovsk Clinical Site 341

Dnipropetrovsk, 49027, Ukraine

Location

Kyiv Clinical Site 344

Kyiv, 03110, Ukraine

Location

Lviv Clinical Site 343

Lviv, 03110, Ukraine

Location

Vinnytsya Clinical Site 342

Vinnytsia, 21005, Ukraine

Location

Related Publications (1)

• Effect of Ceralifimod (ONO-4641), a Sphingosine-1-Phosphate Receptor-1 and -5 Agonist, on Magnetic Resonance Imaging Outcomes in Patients with Multiple Sclerosis: Interim Results from the Extension of the DreaMS Study (P3.161) Amit Bar-Or, Frauke Zipp, Matthew Scaramozza, Timothy Vollmer, Bryan Due, Karthinathan Thangavelu, Tanya Fischer, and Krzysztof Selmaj April 8, 2014 82:10 Supplement P3.161; 1526-632X

  RESULT

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

ceralifimod

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Limitations and Caveats

Company has decided to not pursue phase 3 development of ceralifimod (ONO-4641). The decision was not related to any safety and efficacy findings.

Results Point of Contact

• Title: Merck KGaA Communication Center
• Organization: Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany

service@merckgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  EMD Serono Inc., an affiliate of Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

• Medical Responsible

  Ono Pharmaceutical Co. Ltd

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2010
• First Posted: October 22, 2010
• Study Start: October 1, 2010
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: July 12, 2016
• Results First Posted: July 12, 2016

Record last verified: 2016-06

Locations

CA (5); BE (2); RU (8); DE (4); PL (8); UA (4); CZ (3); GR (1); ES (6); US (20); JP (9)