A Safety and Efficacy Study of FCR001 in Adults With Rapidly Progressive Diffuse Cutaneous Systemic Sclerosis

Key Inclusion Criteria (Recipients):

Age ≥ 18 and < 70 years
Diagnosis of diffuse cutaneous systemic sclerosis
Disease duration < 5 years from first non-Raynaud's phenomenon symptom
Received at least one immunosuppressant in the past to treat the systemic sclerosis (SSc) or currently on an immunosuppressive therapy
Modified Rodnan Skin Score > 15 and < 40

Documented evidence of pulmonary or renal involvement by having at least one of the following:

a) Pulmonary, both required: i. FVC > 45% and < 80% predicted or hemoglobin-adjusted DLco > 45% and < 80% predicted AND ii. Interstitial lung disease evidenced by chest high-resolution computed tomography b) Renal: history of renal crisis that is not active at time of screening. Stable serum creatinine (< 20% increase) must be documented for a minimum of 3 months post-renal crisis at the time of the screening visit.

Key Inclusion Criteria (Donors): Age ≥ 18 and < 60 years

Key Exclusion Criteria (Donor and Recipient):

Use of investigational drugs within 30 days (or within 5 drug half-lives) of signing informed consent
Pregnant or nursing (lactating) woman
Human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) positive. Those with history of HCV infection which was successfully treated and cured may participate
History of malignancy (other than localized squamous or basal cell carcinoma of the skin or in-situ cervical cancer without recurrence) or premalignant syndrome within the past 5 years
Known bone marrow aplasia

Key Exclusion Criteria (Recipient):

Rheumatic disease, other than systemic sclerosis
FVC < 45% of predicted or hemoglobin-adjusted DLco < 45% of predicted
Pulmonary arterial hypertension (PAH)
An LVEF < 50% by echocardiogram or clinical evidence of significant CHF (New York Heart Association Class III or IV) or symptomatic cardiac disease or uncontrolled clinically significant arrhythmias
Estimated GFR < 40 mL/min
Previous treatment with cyclophosphamide, as defined by combination of prior oral and intravenous cyclophosphamide > 9 months, independent of dose
Corticosteroid therapy at prednisone equivalent doses of greater than 10 mg/day, or more than two pulses for concurrent illnesses within prior 12 months
Uncontrolled hypertension
Active gastric antral vascular ectasia, also known as "watermelon stomach"
Use of scleroderma specific therapies beyond protocol specified washout period, except for PDE-5 inhibitors for Raynaud's phenomenon and digital ulcers
Previous history of bone marrow transplant, total lymphoid irradiation, solid organ transplant, autologous or allogeneic hematopoietic progenitor or mesenchymal stem cell transplant
Presence of donor-specific antibodies
Body mass index < 18 or > 35 kg/m^2

Key Exclusion Criteria (Donor): Biologically unrelated female donor to male recipient