Background/Purpose:

We have performed a study to explore safety and tolerability of hyperimmune caprine serum (AIMSPRO®) prepared under GMP conditions in established diffuse cutaneous systemic sclerosis (dcSSc). Potential measures of efficacy and biological activity were also examined.

Methods:

A double-blind parallel group placebo controlled clinical trial was performed under clinical trial authorisation with regulatory authorisation and institutional ethical approval. After informed consent, 20 patients with established dcSSc of greater than 3 years duration not receiving immunosuppressive therapy were randomised to receive either active (n=10) or placebo formulation (n=10) by subcutaneous twice weekly injection over 26 weeks. Clinical assessments evaluated over 26 weeks included modified Rodnan skin score (MRSS), pulmonary function indices and HAQ-DI.

Results:

There were no safety concerns during this study. Frequency of adverse events was not different between active and placebo groups; 154 AE occurred in those receiving placebo and 139 AE in the AIMSPRO® treated subjects. The commonest adverse event was minor injection site reaction occurring in 12 subjects. There were 6 SAE in 3 subjects in the placebo group and 4 SAE in 3 subjects receiving active treatment. No SAE was judged treatment related.

Mean (±SD) baseline MRSS for the study cohort was 15.1 ±7.1, with no significant difference between active or placebo groups. Mean skin score fell by 1.4±4.7 units with active treatment but worsened by 2.1±6.4 units on placebo. This difference did not reach statistical significance (p=0.18, unpaired t-test) but more cases on active treatment showed significant improvement of more than 4 units and over 20% of baseline MRSS (5/10) compared with placebo (1/10; p=0.01, Fisher exact test). HAQ-DI (Mean±SD) at baseline was 1.15±0.07 for active and 1.59±0.63 for placebo group and at 26 weeks was 1.24±0.98 for active and 1.56±0.55 for placebo. These changes were not statistically different (p=0.34, unpaired t-test).

Lung function indices (Table 1) showed a trend of benefit for active treatment compared to the placebo group for those variables that reflect respiratory effort (FVC and FEV1). DLco and TLC did not change during the study.

Table 1:

                                     Baseline                   26 weeks        Units                          p-value

                                                                                                                           (unpaired t-test)

FVC     active              2.68±0.76                  2.76±0.69        Litres                       p=0.06

           placebo           3.12±2.96                  2.96±0.92                                         

FEV1   active              1.99±0.45                  2.02±0.44        Litres                       p=0.10

           placebo           2.31±0.66                  2.21±0.66                                         

DLco   active              5.73±1.80                  5.61±1.87        mmol/min/kPA         p=0.36

           placebo           5.99±2.19                  5.67±2.28                                         

Conclusion:

These results demonstrate tolerability and safety of this novel biological agent in established diffuse cutaneous SSc. The value of a placebo treated control group in small clinical trials evaluating skin disease in SSc is confirmed. Potential improvement in MRSS in cases receiving active therapy and trends of improvement for pulmonary function indices suggest that this intervention may be of clinical benefit and warrants further evaluation.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-placebo-controlled-phase-ii-study-of-hyperimmune-caprine-serum-in-diffuse-cutaneous-systemic-sclerosis-safety-and-potential-efficacy/