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

A Single-arm, Multi-center, Open-label Proof of Concept Safety and Efficacy Study of FCR001 Cell-based Therapy in Adults With Rapidly Progressive Diffuse Cutaneous Systemic Sclerosis at Risk for Organ Failure

This is a multicenter, open-label study to evaluate the safety and tolerability and explore the efficacy of FCR001 cell therapy in adults with rapidly progressive Diffuse Cutaneous Systemic Sclerosis (dcSSc) at risk for organ failure.

The purpose of this multicenter, single-arm study is to evaluate the safety and tolerability and explore the efficacy of FCR001 cell therapy in adults with rapidly progressive dcSSc at risk for organ failure. It consists of 2 years of treatment and 3 years of follow-up, with the primary analysis performed at 24 months.

FCR001 is a cell therapy product that is administered by intravenous (IV) infusion, following nonmyeloablative (NMA) conditioning. It consists of mobilized peripheral blood cells, facilitating cells, and αβ T cells. This therapy is designed to induce donor-specific tolerance by establishing sustained chimerism and to protect against graft versus host disease (GvHD), the major impediment for advancing allogeneic hematopoietic stem cell therapy (HSCT) as a potential therapy in patients.

Key Inclusion Criteria (Recipients):

1. Age ≥ 18 and < 70 years

2. Diagnosis of diffuse cutaneous systemic sclerosis

3. Disease duration < 5 years from first non-Raynaud's phenomenon symptom

4. Received at least one immunosuppressant in the past to treat the systemic sclerosis (SSc) or currently on an immunosuppressive therapy

5. Modified Rodnan Skin Score > 15 and < 40

6. 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):

1. Use of investigational drugs within 30 days (or within 5 drug half-lives) of signing informed consent
2. Pregnant or nursing (lactating) woman
3. 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
4. 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
5. Known bone marrow aplasia

Key Exclusion Criteria (Recipient):

1. Rheumatic disease, other than systemic sclerosis
2. FVC < 45% of predicted or hemoglobin-adjusted DLco < 45% of predicted
3. Pulmonary arterial hypertension (PAH)
4. 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
5. Estimated GFR < 40 mL/min
6. Previous treatment with cyclophosphamide, as defined by combination of prior oral and intravenous cyclophosphamide > 9 months, independent of dose
7. Corticosteroid therapy at prednisone equivalent doses of greater than 10 mg/day, or more than two pulses for concurrent illnesses within prior 12 months
8. Uncontrolled hypertension
9. Active gastric antral vascular ectasia, also known as "watermelon stomach"
10. Use of scleroderma specific therapies beyond protocol specified washout period, except for PDE-5 inhibitors for Raynaud's phenomenon and digital ulcers
11. Previous history of bone marrow transplant, total lymphoid irradiation, solid organ transplant, autologous or allogeneic hematopoietic progenitor or mesenchymal stem cell transplant
12. Presence of donor-specific antibodies
13. Body mass index < 18 or > 35 kg/m^2

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