Minerva Neurosciences (NERV) has officially begun dosing patients for their pivotal phase 3 clinical trial for the negative symptoms or Schizophrenia. Let's examine the primary endpoint in the phase 3 (Marder NSFS) and compare it with their successfully completed phase 2 primary endpoint PANSS Negative Scale (Pentagonal Structure 5-Factor) to see how the items vary. Below is the phase 2.
Phase 2 PANSS Negative Scale (Pentagonal Structure) p = 32mg 64mg
N1 Blunted Affect .25 .17
N2 Emotional Withdrawal .01 .02
N3 Poor Rapport .00 .00
N4 Passive/apathetic social withdraw .29 .01
N6 Lack of spontaneity and flow of conversation .07 .01
G7 Motor retardation .68 .04
G8 Uncooperativeness .41 .86
G13 Disturbance of volition .25 .88
G14 Poor impulse control .89 .56
Phase 2 5-Factor Negative Score
32mg p=0.021 effect size 0.45 64mg p=0.003 effect size 0.58
Below is the phase 3 Marder NSFS (negative symptom factor score) items that will be tested versus placebo.
Phase 2 Marder Negative Symptoms Factor Score (NSFS) p = 32mg 64mg
N1 Blunted Affect .25 .17
N2 Emotional Withdrawal .01 .02
N3 Poor Rapport .00 00
N4 Passive/apathetic social withdraw .29 .01
N6 Lack of spontaneity .07 .01
G7 Motor retardation .68 .04
G16 Active social avoidance .01 .00
Notice that the phase 2 design included G8, G13, and G14, which scored the lowest on effect for the phase 2 primary endpoint, but will not be included in the phase 3 Marder (NSFS) primary endpoint. The currently running phase 3 primary endpoint includes the same items as the phase 2, (minus G8, G13, G14) with the inclusion of G16 (active social avoidance) which scored a .01 and .00 respectively in the phase 2 clinical trial. The Marder items that were included in the phase 2, would have scored better in itself, than the phase 2 primary endpoint PANSS Negative Scale (Pentagonal Structure) 5-Factor Negative Score of p=0.021 and p=0.003, which was achieved with the 32mg and 64mg dose. Thank you for reading.
Phase 2 PANSS Negative Scale (Pentagonal Structure) p = 32mg 64mg
N1 Blunted Affect .25 .17
N2 Emotional Withdrawal .01 .02
N3 Poor Rapport .00 .00
N4 Passive/apathetic social withdraw .29 .01
N6 Lack of spontaneity and flow of conversation .07 .01
G7 Motor retardation .68 .04
G8 Uncooperativeness .41 .86
G13 Disturbance of volition .25 .88
G14 Poor impulse control .89 .56
Phase 2 5-Factor Negative Score
32mg p=0.021 effect size 0.45 64mg p=0.003 effect size 0.58
Below is the phase 3 Marder NSFS (negative symptom factor score) items that will be tested versus placebo.
Phase 2 Marder Negative Symptoms Factor Score (NSFS) p = 32mg 64mg
N1 Blunted Affect .25 .17
N2 Emotional Withdrawal .01 .02
N3 Poor Rapport .00 00
N4 Passive/apathetic social withdraw .29 .01
N6 Lack of spontaneity .07 .01
G7 Motor retardation .68 .04
G16 Active social avoidance .01 .00
Notice that the phase 2 design included G8, G13, and G14, which scored the lowest on effect for the phase 2 primary endpoint, but will not be included in the phase 3 Marder (NSFS) primary endpoint. The currently running phase 3 primary endpoint includes the same items as the phase 2, (minus G8, G13, G14) with the inclusion of G16 (active social avoidance) which scored a .01 and .00 respectively in the phase 2 clinical trial. The Marder items that were included in the phase 2, would have scored better in itself, than the phase 2 primary endpoint PANSS Negative Scale (Pentagonal Structure) 5-Factor Negative Score of p=0.021 and p=0.003, which was achieved with the 32mg and 64mg dose. Thank you for reading.
