A Randomized, Blinded, Parallel Group, Placebo Controlled Pilot Study Evaluating the Effect of PVAC Treatment in Patients with Diffuse Systemic Sclerosis

MARK C. GENOVESE, ELIZA F. CHAKRAVARTY, DAVID L. BOYLE, ZUHRE TUTUNCU, CHRISTINE M. THORBURN, MERITA HALILHODZIC, STEWART KROLL, JAN BAUGHMAN, STANFORD STEWART, and ARTHUR KAVANAUGH

ABSTRACT.

Objective. Systemic sclerosis (SSc) is a disorder characterized by progressive thickening of the skin; there is no effective therapy. PVAC, a potential therapeutic agent derived from delipidated, deglycolipidated Mycobacterium vaccae, has shown effects on cutaneous disease in animal models of SSc. We evaluated the safety and possible biologic effect of intradermal injections of PVAC in patients with diffuse SSc.

Methods. Eighteen patients enrolled in this double blind, placebo controlled, randomized, 24 week pilot study. All patients met criteria for diffuse SSc without evidence of significant renal dysfunction, pulmonary fibrosis, pulmonary hypertension, or congestive heart failure. Patients received 8 intradermal injections of 15 µg PVAC, 50 µg PVAC, or placebo at 3 week intervals. The primary efficacy endpoint was the change in Modified Rodnan Skin Score (MRSS) at Week 24. Each of the active drug arms was compared to placebo.

Results. Baseline demographic and disease characteristics were similar across the 3 treatment groups. The median age was 48 years and 14 of 18 (78%) patients were female. The regimens were well tolerated with no reported serious adverse events; however, grade 1 or 2 injection site reactions occurred in the majority of patients receiving PVAC. The MRSS improved by 20.6% in the 15 µg PVAC arm, while it worsened by 29.8% in the placebo arm and by 16.7% in the 50 µg arm. Change in physician and patient global assessments followed similar trends.

Conclusion. In this pilot study, use of PVAC in patients with SSc appeared safe and was associated with a trend toward improved skin scores in the 15 µg treatment group. Additional evaluation of this therapeutic approach is warranted. (J Rheumatol 2005;32:2345-50)

Key Indexing Terms:

SYSTEMIC SCLEROSIS
SCLERODERMA
CLINICAL TRIAL
MODIFIED RODNAN SKIN SCORE
PVAC
THERAPY

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From the Division of Immunology and Rheumatology, Stanford University, Palo Alto, California; Center for Innovative Therapy, Division of Rheumatology, Allergy, and Immunology, University of California, San Diego, California; and Corixa Corporation, Seattle, Washington, USA.

Supported by Corixa Corporation, Seattle, Washington, USA.

M.C. Genovese, MD, Associate Professor of Medicine; E.F. Chakravarty, MD, Assistant Professor of Medicine; C. Thorburn, MD, Fellow, Division of Immunology and Rheumatology, Stanford University; D. Boyle, BA; Z. Tutuncu, MD; M. Halilhodzic, MD; A. Kavanaugh, MD, Professor of Medicine, Division of Rheumatology, Allergy, and Immunology, University of California; S. Kroll; J. Baughman, PhD; S. Stewart, MD, Corixa Corporation.

Address reprint requests to Dr. M.C. Genovese, 1000 Welch Road, #203, Palo Alto, CA 94304. E-mail: genovese@stanford.edu

Accepted for publication July 21, 2005.

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