Please select the arm or intervention descriptions that belong to the clinical trial below.
Title: A Phase II, Double-blind, Randomized, Multi-center, Adaptive Dose-ranging, Placebo-controlled, Parallel-group Study Evaluating Safety, Tolerability and Efficacy on MRI Lesion Parameters and Determining the Dose Response Curve of BAF312 Given Orally Once Daily in Patients With Relapsing-remitting Multiple Sclerosis.
Brief Summary: The purpose of this study was to determine the dose-response curve for the MRI-based efficacy of BAF312 compared with placebo in patients with Relapsing-Remitting Multiple Sclerosis (RRMS), and to characterize its safety and tolerability for the selection of an optimal dose in a later phase III study.

Study Design Rationale An adaptive design was chosen to characterize the dose response curve of BAF312. In a first period of study ("Period 1"), three doses of BAF312 and placebo were tested for MRI efficacy. Based on an interim analysis (IA) after 3 months of treatment, two additional active doses for period 2 wereselected , thus allowing to optimize the overall determination of the dose response curve with 5 data points of active treatment, and placebo. The doses were kept blinded. The use of Modeling and Simulation allowed to establish the full range and dynamics of the dose-response curve in silico, and hence the definition of the optimal dose for later phase III studies.

The choice of placebo as treatment control was essential to obtain information on the specific compared to non-specific effects of active treatment and provides the best way of evaluating the efficacy and of assessing the true safety and tolerability profile of BAF312. Short-term placebo exposure (6 (Period 1) or 3 (Period 2) months, respectively) was unlikely to lead to longer term differences in outcomes \[Polman, 2008\]. The use of an adaptive design strategy contributed to a significant reduction of placebo exposure, both in terms of the number of patients and duration, as compared to conventional trial models.

Patients having completed the study within the protocol might be eligible for the Extension Phase study where they receive long-term BAF312 treatment (a separate protocol).


Options:
A: Arm Label: BAF312 10 mg/2 mg; Type: EXPERIMENTAL; Interventions: Drug: BAF312 | Arm Label: BAF312 2 mg/2 mg; Type: EXPERIMENTAL; Interventions: Drug: BAF312 | Arm Label: BAF312 1.25 mg/2 mg; Type: EXPERIMENTAL; Interventions: Drug: BAF312 | Arm Label: BAF312 .5 mg/2 mg; Type: EXPERIMENTAL; Interventions: Drug: BAF312 | Arm Label: BAF312 .25 mg/2 mg; Type: EXPERIMENTAL; Interventions: Drug: BAF312 | Intervention Type: DRUG; Name: BAF312; Assigned to Arm(s): BAF312 .25 mg/2 mg, BAF312 .5 mg/2 mg, BAF312 1.25 mg/2 mg, BAF312 10 mg/2 mg, BAF312 2 mg/2 mg
B: Arm Label: BAF312 10mg (period 1); Type: EXPERIMENTAL; Interventions: Drug: BAF312 | Arm Label: BAF312 2 mg (period 1); Type: EXPERIMENTAL; Interventions: Drug: BAF312 | Arm Label: BAF312 0.5 mg (period 1); Type: EXPERIMENTAL; Interventions: Drug: BAF312 | Arm Label: BAF312 dose between 0.1 to 8 mg period 2; Type: EXPERIMENTAL; Interventions: Drug: BAF312 | Arm Label: BAF312 dose between 0.1 - 8 mg period 2; Type: EXPERIMENTAL; Interventions: Drug: BAF312 | Arm Label: Placebo (period 1, 2); Type: PLACEBO_COMPARATOR; Interventions: Drug: Placebo | Intervention Type: DRUG; Name: BAF312; Assigned to Arm(s): BAF312 0.5 mg (period 1), BAF312 10mg (period 1), BAF312 2 mg (period 1), BAF312 dose between 0.1 - 8 mg period 2, BAF312 dose between 0.1 to 8 mg period 2 | Intervention Type: DRUG; Name: Placebo; Assigned to Arm(s): Placebo (period 1, 2)
C: Arm Label: Subjects Assigned to BAF312; Type: N/A; Interventions: Procedure: Blood Draw, Procedure: CSF collection by lumbar puncture (Optional) | Arm Label: Subjects Assigned to Placebo (Controls); Type: N/A; Interventions: Procedure: Blood Draw, Procedure: CSF collection by lumbar puncture (Optional) | Intervention Type: PROCEDURE; Name: Blood Draw; Assigned to Arm(s): Subjects Assigned to BAF312, Subjects Assigned to Placebo (Controls) | Intervention Type: PROCEDURE; Name: CSF collection by lumbar puncture (Optional); Assigned to Arm(s): Subjects Assigned to BAF312, Subjects Assigned to Placebo (Controls)
D: Arm Label: Siponimod (BAF312); Type: EXPERIMENTAL; Interventions: Drug: BAF312 | Arm Label: Placebo; Type: PLACEBO_COMPARATOR; Interventions: Drug: Placebo | Intervention Type: DRUG; Name: BAF312; Assigned to Arm(s): Siponimod (BAF312) | Intervention Type: DRUG; Name: Placebo; Assigned to Arm(s): Placebo

Answer: B