Phase 2 Study
Phase 2 Diffuse Cutaneous Systemic Sclerosis (Scleroderma) Study (Double-Blinded Phase Completed, Open Label Extension Phase Ongoing)
Corbus Pharmaceuticals has reported positive results from the Phase 2 of anabasum in patients with diffuse cutaneous systemic sclerosis. Results indicated a positive clinical benefit for patients who received anabasum compared to placebo.
During the double-blind phase of the study participants were screened for up to 28 days to ensure they met study entry criteria. Following the initial screening, participants were provided a dose of anabasum once a day for 28 days or either anabasum or placebo twice a day for 84 days. On the 29th day, participants who were receiving once a day dosing transitioned to twice a day dosing for 56 days. The total treatment period was 84 days. After the treatment period, participants were followed for an additional 28 days.
- Study participants who completed the first portion of the study had the option of enrolling in an open-label extension to receive anabasum twice a day.
Anabasum successfully achieved the primary objective of the study by demonstrating an acceptable safety and tolerability profile at all doses with no serious or severe adverse events related to the study drug.
During Weeks 1-4 treatment-emergent adverse events (TEAE) were reported in 13 (48.1%) and 6 (40%) of study participants who received anabasum or placebo, respectively. During Weeks 4-12 of this study 12 (44.4%) of participants receiving anabasum and 6 (40%) of study participants receiving placebo reported TEAEs. There were no serious, severe, or unexpected adverse events related to anabasum. The two reported severe TEAEs both occurred in study participants who were receiving placebo. One subject who received anabasum withdrew from the study for an adverse event which was moderate dizziness.
American College of Rheumatology Combined Response Index Systemic Sclerosis (CRISS)
The difference in CRISS scores between anabasum and placebo groups over the trial period was significant (p = 0.044), 1-sided mixed model repeated measures using rank transformed data. The median (25th percentile, 75th percentile) CRISS scores for the combined anabasum group and the placebo group at Weeks 4, 8, 12, and 16 are provided in the table below.
|Group||Median CRISS Score1, % (25th percentile, 75th percentile)|
|Week 4||Week 8||Week 12||Week 16|
n = 26
n = 15
Modified Rodnan Skin Score, SSc Skin Symptoms, 5-D Itch Questionnaire, HAQ-DI, Patient Global Assessment, and Physician Global Assessment
Secondary efficacy outcome measures support the CRISS score findings. Study participants receiving anabasum had a greater improvement in Modified Rodnan Skin Score (MRSS) than study participants receiving placebo. Similar improvements were observed on the SSc Skin Symptoms Questionnaire (p=0.004), and the 5-D Itch Questionnaire (p=0.032). Study participants who received anabasum also had a mean improvement in HAQ-DI, whereas study participants who received placebo had a mean worsening in HAQ-DI score (p=0.03). On the Patient and on the Physician Global Assessment, study participants who received anabasum had a greater improvement.
Molecular Skin Score
The molecular skin score which is a calculation of skin thickening in SSc based on the expression of genes associated with the production of pro-inflammatory and fibrogenic proteins found in skin biopsy samples. Molecular skin scores for study participants who received anabasum improved post-treatment (p=0.0029) versus study participants who received placebo (p=0.9576).
Following the end of Phase 2 meeting with the FDA, the Company is proceeding with plans to initiate a Phase 3 study to support a New Drug Application (NDA) for anabasum for the treatment of diffuse cutaneous systemic sclerosis.
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