Phase 3 Study to Evaluate Efficacy and Safety of NU100 in Patients With Relapsing Remitting Multiple Sclerosis (RRMS)

A Phase 3, Multicenter, Double-blind,Randomized, Placebo-controlled, Parallel-group Study to Evaluate the Safety and Efficacy of NU100 in Patients With Relapsing Forms of Multiple Sclerosis

The purpose of this study is to evaluate the safety and efficacy of NU100 in patients with relapsing remitting multiple sclerosis (RRMS) as compared to placebo and an active comparator. The primary clinical objective selected for this Phase 3 study, the cumulative number of new combined unique active lesions (CALs; defined as new gadolinium T1-weighted lesions and non-enhancing new and newly enlarging T2-weighted lesions) on magnetic resonance imaging (MRI) scans over the course of 4 and 12 months of treatment to demonstrate the superiority of NU100 to placebo and the non-inferiority of NU100 to Betaferon®, respectively.

Inclusion Criteria:

Patients will be eligible to participate in the study if all of the following criteria are met at both screening (V-1) and baseline (V0):

1. Female or male patients, aged between 18 and 60 years, inclusive
2. Signed and dated statement of informed consent
3. Diagnosis of RRMS according to McDonald's Criteria - revision 2010 (Polman et al., 2011)
4. Interferon (IFN) beta-1b naïve
5. Expanded Disability Status Scale (EDSS) score of < 5.5
6. At least 1 documented relapse in the past year (defined as the appearance of a new clinical sign/symptom [one that had been stable for at least 30 days] that persisted for a minimum of 24 hours in the absence of fever) ---or--- a subclinical sign/symptom (defined as a Gd-enhancing lesion or a new T2 lesion demonstrated on MRI examination on a prior MRI that has been completed within 1 year of the screening MRI). The Screening (V-1) MRI should not be used for this determination.
7. No relapse in the 4 weeks prior to the screening visit (V-1).
8. Must be in a clinically stable or improving neurological state 4 weeks preceding the screening visit (V-1).

Exclusion Criteria:

Patients meeting any of the following exclusion criteria at screening (V-1) and baseline (V0) will not be enrolled in the study:

1. Relapse at the baseline visit (V0) or occurring within 4 weeks prior to the screening visit (V-1)

2. Intake of glatiramer acetate within 3 months prior to the screening (V-1) visit

3. Intake of previous immunotherapy or immunosuppressant treatment, within 4 months prior to the screening (V-1) visit

4. Intake of or previously received therapy with cladribine or alemtuzumab

5. An active viral, bacterial, or systemic fungal infection within 1 week of baseline (V0)

6. Use of systemic steroids within 3 weeks prior to the screening (V-1) MRI

7. Progressive disease

8. Level of liver enzymes 2.5 x the upper limit of normal

9. Abnormal renal function (estimated Glomerular Filtration Rate [eGFR] < 60 ml/min/1.73 m2 )

10. Positive serology or history for Hepatitis B, C, or human immunodeficiency virus (HIV)

11. Serious or acute coronary diseases, defined by at least 1 of the following conditions:

    • Clinical symptoms of ischemic heart disease
    • ST elevation or depression > 2 mm on the electrocardiogram (ECG)
    • Clinical symptoms of cardiac failure and/or current medical treatment for cardiac failure
    • Severe ventricular arrhythmia (frequent premature ventricular beats)
    • Atrioventricular block at third level

12. Chronic use of non-steroidal anti-inflammatory drugs

13. History of any of the following:

    • Severe depression or suicide attempt
    • Uncontrolled seizure disorder
    • Cancer, excluding adequately treated basal cell carcinoma of the skin or adequately treated in situ carcinoma of the cervix
    • Previous contrast reaction to gadolinium or any other contraindications to MRI (e.g., metal in the eye, pacemakers, aneurysm clip)

14. Allergy to human albumin or to mannitol

15. Excessive alcohol use or illicit drug use

16. Women who are breast feeding, pregnant, or planning to become pregnant, or are unwilling to use an effective birth control method while on study

17. Medical, psychiatric, or other conditions that compromise the patient's ability to understand the patient information, to give informed consent, to comply with the trial protocol, or to complete the study

18. Participation in any other study involving investigational or marketed products, concomitantly or within 30 days prior to entry in the study Current participation in other clinical trials