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

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.

Study Overview

• Status: Withdrawn
• Conditions: Diffuse Cutaneous Systemic Sclerosis
• Intervention / Treatment: Biological: FCR001

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 Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Operations; Phone Number: (617) 655-7551; Email: freedom-3study@talaristx.com

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Talaris Therapeutics Inc.
• Investigators: Study Director: Joel Weinthal, MD, Talaris Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): November 24, 2021
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: October 20, 2021
• First Submitted That Met QC Criteria: October 20, 2021
• First Posted (Actual): October 28, 2021

Study Record Updates

• Last Update Posted (Actual): October 12, 2023
• Last Update Submitted That Met QC Criteria: October 10, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Allogeneic; Transplant; Scleroderma; Stem cell therapy; Severe scleroderma
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Connective Tissue Diseases; Sclerosis; Scleroderma, Systemic; Scleroderma, Diffuse
• Other Study ID Numbers: FCR001C2201 (FREEDOM-3)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No