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

NCT ID: NCT05098145

Last Updated: 2023-10-12

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-24
• Study Completion Date: 2027-02-28

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.

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.

Conditions

Diffuse Cutaneous Systemic Sclerosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

FCR001

Intervention Type: BIOLOGICAL

Enriched hematopoietic stem cell infusion

Interventions

FCR001

Enriched hematopoietic stem cell infusion

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

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.

Exclusion Criteria

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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Talaris Therapeutics Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joel Weinthal, MD

Role: STUDY_DIRECTOR

Talaris Therapeutics

Locations

University of Michigan

Ann Arbor, Michigan, United States

Countries

United States

Other Identifiers

FCR001C2201 (FREEDOM-3)

Identifier Type: -

Identifier Source: org_study_id