Open Label Extension Study of Brentuximab Vedotin in Early dcSSc

Skin improvement is defined as the mean mRSS decrease of ≥8 points

modified Rodnan Skin Score (mRSS): is a standard outcome measure for skin disease in SSc and calculated by measuring skin thickness in 17 different body sites (each site scored 0-3, with a total possible additive score of 51). A higher skin score (or a higher "skin thickness") and progression of this score, is predictive of internal organ involvement and mortality. While a lower or improving (lessening) score is associated with favorable outcomes, including better survival.

modified Rodnan Skin Score (mRSS): is a standard outcome measure for skin disease in SSc and calculated by measuring skin thickness in 17 different body sites (each site scored 0-3, with a total possible additive score of 51). A higher skin score (or a higher "skin thickness") and progression of this score, is predictive of internal organ involvement and mortality. While a lower or improving (lessening) score is associated with favorable outcomes, including better survival.

Measured on a Visual Analogue Scale (VAS) from 0-10, with 0 being no disease activity and 10 being the worst possible disease activity.

Measured on a Visual Analogue Scale (VAS) from 0-10, with 0 being no disease severity and 10 being the worst possible disease severity.

Measured on a Visual Analogue Scale (VAS) from 0-10, with 0 being no disease damage and 10 being the worst possible disease damage.

Measured on a Visual Analogue Scale (VAS) from 0-100, with 0 being no overall effect of disease on participant, and 100 being the worst possible overall effect of disease on participant.

This is a patient reported outcome.

The SHAQ combines the disability and pain scales of the HAQ (HAQ-DI), with five scleroderma-specific Visual Analogue Scales for: digital ulcers, Raynaud's phenomenon, gastrointestinal (GI) symptoms, lung symptoms, and overall disease severity.

The HAQ-DI yields a score of 0-3, that indicates the extent of the respondent's functional limitations.

Each VAS score is scaled from 0 to 3, with 0 being no symptoms and 3 being the worst possible symptom severity.

A composite VAS score is not created nor are the individual VAS scores incorporated into the HAQ DI score. Typically, each VAS score is reported individually. There is a proposed way to obtain a combined score obtained by pooling the 8 domains of the HAQ DI and the 5 VASs; however, this approach has not yet been widely accepted.

This is a patient reported outcome.

Change in Pulmonary Function as measured by percentage of Improving or worsening DLCO.

The DLCO (diffusing capacity of the lungs for carbon monoxide) measures the ability of the lungs to transfer gas from inhaled air to the red blood cells in pulmonary capillaries.

% Improving/worsening DLCO. Analyzed as an ordinal outcome.

*PFT (pulmonary function test) results will only be analyzed as available under standard of care.

Change in Pulmonary Function as measured by percentage of Improving or worsening FVC.

The FVC (Forced vital Capacity) is the total amount of air exhaled during the FEV (Forced expiratory volume) test.

% Improving/worsening FVC. Analyzed as an ordinal outcome.

*PFT (pulmonary function test) results will only be analyzed as available under standard of care.

To define disease progression

CRISS score: It is calculated according to changes from the start of a study, compared to an endpoint, by using the modified Rodnan Skin Score (mRSS), the Health Assessment Questionnaire - Disability Index (HAQ-DI), patient and physician global assessment of scleroderma-related health, and forced vital capacity. A CRISS score of ≥ 0.6 indicates likelihood that a patient improved on treatment.

Change in serum concentrations of the acute phase reactant, CRP

CRP aids in the evaluation of stress, trauma, infection, inflammation, surgery & associated diseases. Blood levels of C-Reactive Protein (CRP) are known to rise in acute disease to a level of up to 50 mg/L in the presence of slight to moderate inflammatory process. Values >50 mg/L indicate high and extensive inflammatory activity.

Change in serum concentrations of the acute phase reactant, ESR

Reference ranges:

Male: 0-10 mm/h Female: 0-20 mm/h

A faster-than-normal rate may indicate inflammation in the body. Inflammation is part of the immune response system. The higher the number, the higher the likelihood of inflammation.

Defined as Adverse Events (AEs) >= Grade 3 and assessed by the investigator as 1 of the following: related or unrelated to treatment.

Any infectious complication will be tracked under Adverse Event recording

interleukin 2 receptor (sIL-2R)

Serum sIL-2R level is a sensitive and quantitative marker of circulating peripheral blood mononuclear cell activation.

Normal range of serum sIL-2R is below 2500 pg/ml. High levels may be found in conditions associated with T-cell activation.

Changes in serum amino-terminal propeptide of type III collagen levels.

Amino-terminal propeptide of procollagen type III (PIIINP) is generated during the synthesis of type III collagen. PIIINP is a non-specific marker of soft tissue injury.

PIIINP in serum has been shown to correlate with fibrillogenesis, and thus to be a potential direct marker of type III collagen deposition.

PIIINP reference range Adult (>19 years): 1.2 - 4.2 ug/L

and myofibroblast score in skin biopsies (24 and 48 weeks) if the study looks favorable with respect to potential benefit and safety.

Measured by immunohistochemistry (IHC) as the percentage of CD30-positive cells per total number of cells/mm2.

Reference rage not established (there is no range, we are looking for a stat significant change (decrease) from baseline)