Active-controlled phase IIIb study to investigate the ability of the HAP score to predict responders to Octagam 5% in patients with early relapsing multiple sclerosis.

INTERVENTION: Trade Name: Octagam 50 mg/ml Pharmaceutical Form: Solution for infusion INN or Proposed INN: Human normal immunoglobulin CAS Number: 308067‐58‐5 Current Sponsor code: Octagam 5% Other descriptive name: IMMUNOGLOBULIN G Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 50‐ Trade Name: Copaxone 20 mg/ml Pharmaceutical Form: Solution for injection in pre‐filled syringe INN or Proposed INN: glatiramer acetate CAS Number: 147245‐92‐9 Other descriptive name: GLATIRAMER ACETATE Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 20‐ Trade Name: Rebif 44 micrograms Pharmaceutical Form: Solution for injection in pre‐filled syringe INN or Proposed INN: INTERFERON BETA‐1a CAS Number: 145258‐61‐3 Concentration unit: million IU million international units Concentration type: equal Concentration number: 12‐ Trade Name: Betaferon 250 microgram/ml Pharmaceutical Form: Powder and solvent for solution for injection INN or Proposed INN: INTERFERON BETA‐1b CAS Number: 145155‐23‐3 Concentration unit: µg/ml microgram(s)/millilitre Concentration type: equal Concentration number: 250‐ CONDITION: relapsing multiple sclerosis ; MedDRA version: 19.0 Level: PT Classification code 10063399 Term: Relapsing‐remitting multiple sclerosis System Organ Class: 10029205 ‐ Nervous system disorders Therapeutic area: Diseases [C] ‐ Nervous System Diseases [C10] PRIMARY OUTCOME: Main Objective: To investigate the ability of the HAP score to accurately predict responders to Octagam 5% Primary end point(s): Superiority with regard to decreased ARR of Octagam 5% treatment in patients pre‐classified as predicted responders (“RO”) compared to predicted nonresponders (“NRO”) to Octagam 5% treatment Secondary Objective: • To verify that Octagam 5% in predicted responders is of at least similar effectiveness as the first‐line therapies IFN‐ß sc or GA • To verify that the HAP score result is of no predictive power for the ARR in IFN‐ß sc or GA treated patients • To evaluate the assumption that the HAP score truly predicts the effectiveness of treatment with Octagam 5% and not the progress of disease as such • To investigate the proportion of patients responding to IMP treatment vs. patients not responding • To investigate the effect of IMP treatment on the time to first medically confirmed relapse after 3‐month run‐in phase • To investigate the effect of IMP treatment on the level of disability, evaluated by means of the EDSS and the MSFC score • To investigate the effect of IMP treatment on the brain by means of MRI parameters (lesion number and volume; whole brain volume) • To investigate the effect of IMP treatment on health‐related QoL • To investigate the safety and tolerability of IMP treatment Timepoint(s) of evaluation of this end point: Continuously SECONDARY OUTCOME: Secondary end point(s): Secondary efficacy endpoints are: ; • ARR of Octagam 5% treatment compared to active control (first‐line therapy: IFN‐ß sc or GA) ; • ARR of IFN‐ß sc or GA treatment compared between predicted responders (“RI/G”) and non‐responders (“NRI/G”) to Octagam 5% treatment ; • Compare ARR of “RO” with both IMP treatment arms combined (“RI/G” and “NRI/G”) ; • Time from randomisation to first medically confirmed relapse after 3‐month run‐in phase ; • Time from last relapse before enrolment to first medically confirmed relapse after 3‐month run‐in phase ; • Progression of the disease (defined as an increase of the EDSS), confirmed at 2 separate assessments at least 12 weeks apart ; • Change in MSFC ; • Health‐related Quality of Life assessed by MSQOL‐54 ; Secondary safety endpoints are: ; • Adverse event (AE) monitoring ; • Vital signs (blood pressure, heart rate, body temperature and respiratory rate) ; • Percentage of actual responders and non‐responders in the 21‐month period between 3 months after first study treatment administration (“run‐in” phase) and the end of treatment period at month 24) ; • Cerebral MRI assessments: number and volumes of Gadolinium‐diethylenetriamine penta‐acetic acid (Gd‐DTPA) enhancing lesions with T1 weighted imaging; number of new and enlarging T2 lesions; number of new T1 Black Holes; volumes of T1 and T2 lesions; whole brain volume ; • Standard laboratory safety tests (clinical chemistry and haematology) Timepoint(s) of evaluation of this end point: Continuously INCLUSION CRITERIA: 1) Patients aged =18 years 2) Early diagnosed relapsing form of MS (= 5years) according to the revised McDonald criteria (1‐3) 3) Patients who are at least 3 months on stable dosage of either IFN‐ß sc or GA and who did NOT receive the other first‐line therapy before, OR patients who are treatment naive 4) Kurtzke’s EDSS =3.5 5) Patients who experienced at least one medically confirmed relapse during the last 12 months or at least two such relapses in the last 24 months prior to study entry (but not within 30 days between last steroid treatment of relapse and start of screening; subjects who relapse during the screening phase can be re‐screened, once the relapse has resolved but earliest 30 days after the end of relapse treatment with steroids) or at least 1 T1 Gd+ lesion at screening 6) Voluntarily given, fully informed written consent obtained from patient before any study‐related procedures are conducted 7) Patient must be capable