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

Diffuse Cutaneous Systemic Sclerosis Clinical Trial

— FREEDOM-3  

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05098145
• Other study ID #: FCR001C2201 (FREEDOM-3)
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: November 24, 2021
• Est. completion date: February 2027

Study information

• Verified date: October 2023
• Source: Talaris Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: February 2027
• Est. primary completion date: November 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Diffuse Cutaneous Systemic Sclerosis
• Scleroderma, Diffuse
• Scleroderma, Systemic
• Sclerosis

Intervention

Biological:
• FCR001
Enriched hematopoietic stem cell infusion

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Talaris Therapeutics Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of recipient adverse events (AEs)		From day before infusion to 60 months
Primary	Incidence of recipient serious adverse events (SAEs)		From day before infusion to 60 months
Primary	Occurrence of Graft versus Host Disease (GvHD)		From infusion to 60 months
Primary	Time to neutrophil recovery		From infusion to 28 days
Primary	Time to platelet recovery		From infusion to 28 days
Secondary	Percent donor whole blood chimerism		From infusion to 60 months
Secondary	Percentage of donor T-cell chimerism		From infusion to 60 months
Secondary	Incidence of donor AEs		From donation to 12 months
Secondary	Incidence of donor SAEs		From donation to 12 months