FREEDOM-3: A Safety and Efficacy Study of FCR001 in Adults With Rapidly Progressive Diffuse Cutaneous Systemic Sclerosis

Sponsor

Talaris Therapeutics Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05098145

Collaborator

(none)

Enrollment

Location

Arm

62.3

Anticipated Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Diffuse Cutaneous Systemic Sclerosis	Biological: FCR001	Phase 1/Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

18 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Nov 24, 2021

Anticipated Primary Completion Date :

Nov 1, 2026

Anticipated Study Completion Date :

Feb 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: FCR001 FCR001 is a cryopreserved allogeneic stem cell therapy derived from mobilized peripheral blood cells and delivered as a single infusion with a nonmyeloablative conditioning regimen.	Biological: FCR001 Enriched hematopoietic stem cell infusion

Arm

Intervention/Treatment

Experimental: FCR001

FCR001 is a cryopreserved allogeneic stem cell therapy derived from mobilized peripheral blood cells and delivered as a single infusion with a nonmyeloablative conditioning regimen.

Biological: FCR001

Enriched hematopoietic stem cell infusion

Outcome Measures

Primary Outcome Measures

Incidence of recipient adverse events (AEs) [From day before infusion to 60 months]
Incidence of recipient serious adverse events (SAEs) [From day before infusion to 60 months]
Occurrence of Graft versus Host Disease (GvHD) [From infusion to 60 months]
Time to neutrophil recovery [From infusion to 28 days]
Time to platelet recovery [From infusion to 28 days]

Secondary Outcome Measures

Percent donor whole blood chimerism [From infusion to 60 months]
Percentage of donor T-cell chimerism [From infusion to 60 months]
Incidence of donor AEs [From donation to 12 months]
Incidence of donor SAEs [From donation to 12 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

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