A Phase 2 Study of Cladribine Add-on to Interferon-beta (IFN-beta) Therapy in Multiple Sclerosis (MS) Subjects With Active Disease (ONWARD)

NCT00436826 | Completed Phase 2 Results

• 2 other identifiers: 265932006-003366-33
• Study Type: interventional
• Target: 172
• Locations: 4 countries
• Sites: 39

Brief Summary

The goal of this study was to evaluate the safety, tolerability and effectiveness of oral cladribine when taken in combination with Interferon-beta (IFN-beta) therapy for the treatment of multiple sclerosis (MS). This study randomized around 200 participants from approximately 50 sites located world-wide, who have experienced at least one relapse while taking IFN-beta therapy within 48 weeks prior to Screening, irrespective of disability progression. Secondary progressive multiple sclerosis (SPMS) participants, who were still experiencing relapses, and participants who have received disease modifying drugs (DMDs), other than IFN-beta therapy, during their MS treatment history, but were currently on IFN-beta therapy and have experienced active MS symptoms (at least 1 relapse) during the 48 weeks prior to Screening, were enrolled. Participants were randomized in a 2:1 fashion to receive up to 4 cycles of oral cladribine or matching placebo in combination with IFN-beta therapy. Participants who completed the double-blind portion of the study were invited to participate in an open-label extension phase of matching study design.

Conditions

Multiple Sclerosis

Keywords

Multiple Sclerosis; Relapsing forms; Interferon-beta therapy

Outcome Measures

Primary Outcomes (27)

• Double Blind Period: Percentage of Participants With Grade 3 or 4 (Common Terminology Criteria for Adverse Events [CTCAE] v 4.0) Hematological or Liver Toxicity

  Percentage of participants with Grade 3 or 4 CTCAE v 4.0 toxicity on the following hematology and liver function parameters were reported: lymphocytes, cluster of differentiation 4 (CD4) cell, neutrophils, white blood cells, hemoglobin, Alanine transaminase (ALT), Aspartate transaminase (AST), Platelets and Bilirubin. According to CTCAE v 4.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death.

  Baseline up to Week 96

• Double Blind Period: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) in Infections and Infestations System Organ Class (SOC)

  An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. 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 or was otherwise considered medically important. An AE was considered as 'treatment emergent' if it occurred after the first drug administration of each period or if it was present prior to drug administration but exacerbated after the drug administration.TEAEs were entered in infections and infestations SOC as per medical dictionary for regulatory activities (MedDRA) version 11.0

  Baseline up to Week 96

• Double Blind Period: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs

  An AE was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered. SAE: Any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition. An AE was considered as 'treatment emergent' if it occurred after the first drug administration of each period or if it was present prior to drug administration but exacerbated after the drug administration. TEAEs included both Serious TEAEs and non-serious TEAEs.

  Baseline up to Week 96

• Double Blind Period: Time to First Grade 3 or 4 Hematological Toxicity or Liver Toxicity

  Time to first Grade 3 or 4 hematological toxicity or liver toxicity (lymphocytes, cluster of differentiation 4 (CD4) cell, neutrophils, white blood cells, hemoglobin, Alanine transaminase (ALT), Aspartate transaminase (AST), Platelets and Bilirubin) were estimated using the Kaplan-Meier method. According to CTCAE v 4.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. 10th and 20th percentiles estimated from Kaplan-Meier survival curve. Due to the small number of events, estimates from Kaplan-Meier survival curves could only be derived for lower percentiles. The median (50th percentile) could not be estimated if less than 50% of the participants had an event during the time of the study. Accordingly, lower percentiles are presented according to the number of events observed.

  Baseline up to Week 96

• Double Blind Period: Time to Recovery From Grade 3 or 4 Hematological Toxicity

  Time to recovery from grade 3 or 4 hematological were reported: lymphocytes, platelets, neutrophils, white blood cells and hemoglobin. According to CTCAE v 4.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. Recovery" as "Recovery from a Grade 3 or 4 toxicity is defined as a return to a Grade 0 or 1.

  Baseline up to Week 96

• Double Blind Period: Mean Changes in Lymphocytes, White Blood Cells (WBC), Neutrophils and Platelets Values From Baseline to Week 96

  Mean changes in lymphocytes, WBC, neutrophils and platelets from baseline to week 96 were reported.

  Baseline, Week 96

• Double Blind Period: Maximum Corrected QT Interval (QTc)

  Criteria for potential clinical concern in ECG parameters: Maximum corrected QT interval (QTc) in range of 450 to less than 480 millisecond (msec).

  Baseline up to Week 96

• Double Blind Period: Mean Change From Baseline in Vital Signs- Systolic and Diastolic Blood Pressure

  Mean change from baseline in vital signs- systolic and diastolic blood pressure was reported.

  Baseline, Week 96

• Double Blind Period: Mean Change From Baseline in Vital Signs- Pulse Rate

  Mean change from baseline in vital signs- Pulse Rate was reported.

  Baseline, Week 96

• Double Blind Period: Mean Change From Baseline in Vital Signs- Weight

  Mean change from baseline in vital signs- weight was reported.

  Baseline, Week 96

• Double Blind Period: Mean Change From Baseline in Vital Signs- Temperature

  Mean change from baseline in vital signs- temperature was reported.

  Baseline, Week 96

• Double Blind Period: Mean Change From Baseline in Electrocardiogram (ECG) Parameters- Heart Rate

  Mean change from baseline in ECG parameters- Heart Rate was reported.

  Baseline, Week 96

• Double Blind Period: Mean Change From Baseline in Electrocardiogram (ECG) Parameters- PR, RR, QRS and OT Interval

  Mean change from baseline in ECG parameters- PR, RR, QRS and OT interval was reported.

  Baseline, Week 96

• Double Blind Period: Mean Changes From Baseline in Hemoglobin Level to Week 96

  Mean changes in hemoglobin level from baseline to week 96 was reported.

  Baseline, Week 96

• Double Blind Period: Mean Changes From Baseline in CD4+ Count, CD8+ Count, and CD19+ to Week 96

  Mean changes CD4+ Count, CD8+ Count, and CD19+ from baseline to Week 96 were reported.

  Baseline, Week 96

• Double Blind Period: Mean Changes From Baseline in Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) to Week 96

  Mean changes in ALT and AST from baseline to week 96 were reported.

  Baseline, Week 96

• Open Label Extension Period: Maximum Corrected QT Interval (Qtc)

  Criteria for potential clinical concern in ECG parameters: Maximum corrected QT interval (QTc) in range of 450 to less than 480 millisecond (msec).

  Baseline up to Week 96

• Open Label Extension Period: Mean Change From Baseline in Vital Signs- Systolic and Diastolic Blood Pressure

  Mean change from baseline in vital signs- systolic and diastolic blood pressure was reported.

  Baseline, Week 72

• Open Label Extension Period: Mean Change From Baseline in Vital Signs- Pulse Rate

  Mean change from baseline in vital signs- Pulse Rate was reported.

  Baseline, Week 72

• Open Label Extension Period: Mean Change From Baseline in Vital Signs- Weight

  Mean change from baseline in vital signs- weight was reported.

  Baseline, Week 72

• Open Label Extension Period: Mean Change From Baseline in Vital Signs- Temperature

  Mean change from baseline in vital signs- temperature was reported.

  Baseline, Week 72

• Open Label Extension Period: Mean Change From Baseline in Electrocardiogram (ECG) Parameters- Heart Rate

  Mean change from baseline in ECG parameters- Heart Rate was reported.

  Baseline, Week 72

• Open Label Extension Period: Mean Change From Baseline in Electrocardiogram (ECG) Parameters- PR, RR, QRS and OT Interval

  Mean change from baseline in ECG parameters- PR, RR, QRS and OT interval was reported.

  Baseline, Week 72

• OLE and Safety Follow-up Period: Percentage of Participants With Grade 3 or 4 (Common Terminology Criteria for Adverse Events [CTCAE] v 4.0) Hematological or Liver Toxicity

  Percentage of participants with Grade 3 or 4 CTCAE v 4.0 toxicity on the following hematology and liver function parameters were reported: lymphocytes, cluster of differentiation 4 (CD4) cell, neutrophils, white blood cells, hemoglobin, Alanine transaminase (ALT), Aspartate transaminase (AST), Platelets and Bilirubin. According to CTCAE v 4.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death.

  Baseline (OLEP) up to Week 96

• OLE and Safety Follow-up Period: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) in Infections and Infestations System Organ Class (SOC)

  An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. 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 or was otherwise considered medically important. An AE was considered as 'treatment emergent' if it occurred after the first drug administration of each period or if it was present prior to drug administration but exacerbated after the drug administration.TEAEs were entered in infections and infestations SOC as per medical dictionary for regulatory activities (MedDRA) version 11.0

  Baseline (OLEP) up to Week 96

• OLE and Safety Follow-up Period: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs

  An AE was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered. SAE: Any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition. An AE was considered as 'treatment emergent' if it occurred after the first drug administration of each period or if it was present prior to drug administration but exacerbated after the drug administration. TEAEs included both Serious TEAEs and non-serious TEAEs.

  Baseline (OLEP) up to Week 96

• Open Label Extension Period: Time to First Grade 3 or 4 Hematological Toxicity or Liver Toxicity

  Time to first Grade 3 or 4 hematological toxicity or liver toxicity (lymphocytes, cluster of differentiation 4 (CD4+) cell, neutrophils, white blood cells, hemoglobin, Alanine transaminase (ALT), Aspartate transaminase (AST), Platelets and Bilirubin) were estimated using the Kaplan-Meier method. According to CTCAE v 4.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. 10th and 20th percentiles estimated from Kaplan-Meier survival curve. Due to the small number of events, estimates from Kaplan-Meier survival curves could only be derived for lower percentiles. The median (50th percentile) could not be estimated if less than 50% of the participants had an event during the time of the study. Accordingly, lower percentiles are presented according to the number of events observed.

  Baseline up to Week 96

Secondary Outcomes (12)

• Double Blind Period: Number of Combined Unique Active (CUA) Lesions, Active Time Constant 2 (T2) Lesions, and Time Constant 1 (T1) Gadolinium Enhanced (Gd+) Lesions Per Participant Per Scan

  Week 96

• Double Blind Period: Mean Number of T1 Hypointense Lesions Per Participant Per Scan at Week 96

  Week 96

• Double Blind Period: Percentage of Participants With no Active T2 Lesions at Week 96

  Week 96

• Double Blind Period: Percentage of Participants With no Active T1 Gd-Enhanced Lesions at Week 96

  Week 96

• Double Blind Period: Mean Change in T2 Lesion Volume From Baseline to Week 96

  Baseline, Week 96

Study Arms (6)

Cladribine 3.5 mg/kg, IFN-beta (DB period)

EXPERIMENTAL

Participants received cladribine tablets orally as cumulative dose of 0.875 mg/kg over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 milligram per kilogram (mg/kg) along with interferon (IFN)-beta therapy (Rebif® new formulation \[RNF\] 44 mcg three times a week, subcutaneously; Avonex® 30 microgram (mcg) every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the Double blind period (DBP) of 96 weeks.

Drug: Cladribine; Drug: Interferon-beta (IFN-beta)

Placebo, IFN-beta (DB period)

PLACEBO COMPARATOR

Participants received matching placebo tablets orally over a course of 4-5 consecutive days at Week 1, 5, 48, and 52 along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during the DB period of 96 weeks.

Drug: Placebo; Drug: Interferon-beta (IFN-beta)

Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)

EXPERIMENTAL

Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the open label (OL) extension (Ext.) period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.

Drug: Cladribine; Drug: Interferon-beta (IFN-beta)

Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)

PLACEBO COMPARATOR

Participants who received placebo initially and completed DB period entered in the OL Ext. period. In OL Ext. period, participant who met the eligibility criteria received OL oral cladribine 3.5 mg/kg over maximum of 48 weeks along with IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.

Drug: Cladribine; Drug: Placebo; Drug: Interferon-beta (IFN-beta)

Cladribine 3.5 mg/kg, IFN-beta (Safety follow up)

EXPERIMENTAL

Participants who received cladribine 3.5 mg/kg initially and completed DB period entered in the OL ext. safety follow up period. In this period, participants who did not meet eligibility criteria received only IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.

Drug: Cladribine; Drug: Interferon-beta (IFN-beta)

Placebo, IFN-beta (Safety follow up)

PLACEBO COMPARATOR

Participants who received placebo initially and completed DB period entered in the OL ext. safety follow up period. In this period, participants who did not meet eligibility criteria received only IFN-beta therapy (RNF 44 mcg three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) up to 48 weeks.

Drug: Placebo; Drug: Interferon-beta (IFN-beta)

Interventions

Cladribine DRUG

Participants were administered with cladribine tablets orally as cumulative dose.

Cladribine 3.5 mg/kg, IFN-beta (DB period); Cladribine 3.5 mg/kg, IFN-beta (Safety follow up); Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext); Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)

Placebo DRUG

Participants were administered with placebo orally.

Placebo, IFN-beta (DB period); Placebo, IFN-beta (Safety follow up); Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)

Interferon-beta (IFN-beta) DRUG

Participants received IFN-beta therapy (Rebif® new formulation \[RNF\] 44 microgram \[mcg\] three times a week, subcutaneously; Avonex® 30 mcg every week, intramuscularly; or Betaseron® 250 mcg every other day, subcutaneously) during both DB period of 96 weeks and OL extension period of 48 weeks.

Also known as: Avonex®, Betaseron®, RNF

Cladribine 3.5 mg/kg, IFN-beta (DB period); Cladribine 3.5 mg/kg, IFN-beta (Safety follow up); Cladribine 3.5 mg/kg, IFN-beta, Cladribine 3.5 mg/kg (OL Ext); Placebo, IFN-beta (DB period); Placebo, IFN-beta (Safety follow up); Placebo, IFN-beta, Cladribine 3.5 mg/kg (OL Ext)

Eligibility Criteria

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

You may qualify if:

• Be male or female, 18 to 65 years of age (inclusive)
• Weigh between 40 to 120 kilogram (kg), (inclusive)
• Have definite MS, as confirmed by the revised McDonald criteria 2005, and have relapsing forms of MS, such as relapsing-remitting multiple sclerosis (RRMS) or SPMS with superimposed relapses
• Have experienced at least one relapse within 48 weeks prior to Screening, while receiving IFN-beta treatments (Rebif® 44mcg three times a week, subcutaneously; Avonex®30 mcg every week, intramuscular; or Betaseron® 250 mcg every other day, subcutaneously)
• Have a minimum time on IFN-beta therapy of 48-consecutive weeks prior to Screening. Participants who switched from one IFN-beta therapy to another in the 48 weeks preceding Screening may be entered into the study if they have been on a stable regimen of their current IFN-beta therapy for a minimum of 3 months prior to Screening
• Be clinically stable (other than MS relapse) during the 28 days preceding Screening
• The following hematological parameters must be normal (as defined below, inclusively) within 28 days of first dosing of blinded study medication at study day 1 (SD 1)
• Hemoglobin=11.6 to 16.2 gram per deciliter (g/dL)
• Leukocytes (total white blood cells \[WBC\])=4.1 to 12.3\*10\^3 per microliter (/UL)
• Absolute lymphocytes count (ALC)= 1.02 to 3.36\*10\^3/UL
• Absolute neutrophil count (ANC)=2.03 to 8.36\*10\^3/UL
• Platelet count=140 to 450\*10\^3/UL
• Have no medical history or evidence of latent tuberculosis infection (LTBI) or active tubercular disease (TB), as evidenced by TB skin test or chest X-ray
• Have an expanded disability status scale (EDSS) from 1.0-5.5, inclusive
• Have no prior exposure to immunosuppressive or cytotoxic agents (with the exception of steroids for MS flare management, or intravenous immunoglobulin-G \[IVIG\] after allowed wash-out periods

You may not qualify if:

• Have voluntarily provided written informed consent, including, for United states of America (USA), participant authorization under Health Insurance Portability and Accountability Act (HIPAA), prior to any study-related procedure that is not part of normal medical care, and with the understanding that the participant may withdraw consent at any time without prejudice to future medical care
• Has primary progressive multiple sclerosis (PPMS) or SPMS without relapses forms
• Has prior or current malignancy other than medically documented complete excision of basal cell skin cancer no less than 5 years prior to Screening
• Has a history of chronic or clinically significant hematological abnormalities
• Prior use of cladribine, fingolimod, teriflunimide, laquinimod, mitoxantrone, campath-1h, cyclophosphamide, azathioprine, methotrexate, daclizumab, natalizumab, lymphoid irradiation, bone marrow transplantation or myelosuppressive/cytotoxic therapy
• Use of cytokine or anti-cytokine therapy or plasmapheresis within 3 months prior to SD 1
• Treatment with IVIG within 30 days of Screening
• Treatment with oral or parenteral corticosteroids 30 days of Screening
• Treatment with adrenocorticotropic hormone within 28 days prior to SD 1
• Use of any investigational drug (other than Rebif® New Formulation \[RNF\], Avonex® or Betaferon®) or experimental procedure within 6 months prior to SD 1
• Has inadequate liver function, defined by a total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) or alkaline phosphatase greater than 2.5 times the upper limit of the normal values
• Suffers from major medical illness such as cardiac, endocrinologic, hepatic, immunologic (other than MS), metabolic, renal, pulmonary, gastrointestinal, dermatologic, or other major disease that would preclude the administration of oral cladribine
• Suffers from major psychiatric illness (including history of, or current, severe depressive disorders and/or suicidal ideation) that in the opinion of the investigator creates undue risk to the participant or could affect compliance with the study protocol
• Has history of active or chronic infectious disease or any disease which compromises immune function (for example, human immunodeficiency virus \[HIV\]+, human T-lymphotropic virus \[HTLV-1\], Lyme disease, LTBI or TB)
• Has an allergy or hypersensitivity to gadolinium, to cladribine or any of its excipients, or IFN-beta or any of its excipient(s)

Sponsors & Collaborators

• EMD Serono Research & Development Institute, Inc.: lead

Study Sites (39)

Research Site

Cullman, Alabama, United States

Location

Research Site

Phoenix, Arizona, United States

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Research Site

Scottsdale, Arizona, United States

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Research Site

Los Angeles, California, United States

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Boulder, Colorado, United States

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Fort Collins, Colorado, United States

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Research Site

Tampa, Florida, United States

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Atlanta, Georgia, United States

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Research Site

Peoria, Illinois, United States

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Boston, Massachusetts, United States

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St Louis, Missouri, United States

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Newark, New Jersey, United States

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Research Site

Albuquerque, New Mexico, United States

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Charlotte, North Carolina, United States

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Research Site

Winston-Salem, North Carolina, United States

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Research Site

Bethlehem, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Nashville, Tennessee, United States

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Houston, Texas, United States

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Round Rock, Texas, United States

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Burlington, Vermont, United States

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Fidenza, Italy

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Milan, Italy

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Napoli, Italy

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Rome, Italy

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Arkhangelsk, Russia

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Kazan', Russia

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Moscow, Russia

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Novosibirsk, Russia

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Saint Petersburg, Russia

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Samara, Russia

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Smolensk, Russia

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Alicante, Spain

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Research site

Barcelona, Spain

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Bilbao, Spain

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Madrid, Spain

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Málaga, Spain

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Santiago, Spain

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Seville, Spain

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Related Publications (2)

• Giovannoni G, Galazka A, Schick R, Leist T, Comi G, Montalban X, Damian D, Dangond F, Cook S. Pregnancy Outcomes During the Clinical Development Program of Cladribine in Multiple Sclerosis: An Integrated Analysis of Safety. Drug Saf. 2020 Jul;43(7):635-643. doi: 10.1007/s40264-020-00948-x.

  PMID: 32447743 DERIVED

• Montalban X, Leist TP, Cohen BA, Moses H, Campbell J, Hicking C, Dangond F. Cladribine tablets added to IFN-beta in active relapsing MS: The ONWARD study. Neurol Neuroimmunol Neuroinflamm. 2018 Jul 11;5(5):e477. doi: 10.1212/NXI.0000000000000477. eCollection 2018 Sep.

  PMID: 30027104 DERIVED

Related Links

• Trial Awareness and Transparency website
• US Medical Information website, Medical Resources

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Cladribine; Interferon-beta; Interferon beta-1a; Interferon beta-1b

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxyadenosines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Limitations and Caveats

The 96-week DB treatment period of study was completed as planned, and safety and exploratory efficacy results are presented here. The duration of OL Ext. period was reduced for some participants, following termination of the development program.

Results Point of Contact

• Title: Communication Center
• Organization: Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

  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: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2007
• First Posted: February 19, 2007
• Study Start: November 30, 2006
• Primary Completion: September 30, 2011
• Study Completion: March 31, 2012
• Last Updated: October 12, 2020
• Results First Posted: July 1, 2013

Record last verified: 2020-10

Locations

ES (7); US (21); IT (4); RU (7)