Study of Safety, Tolerability and Efficacy of DFV890 in Participants With Familial Cold Auto-inflammatory Syndrome (FCAS) (DFV890-FCAS)

An Open-label, Single Arm Phase II Study of DFV890 to Assess the Safety, Tolerability and Efficacy in Participants With Familial Cold Auto-inflammatory Syndrome (FCAS)

The purpose of this phase II study was to assess the safety, tolerability and efficacy of DFV890 in participants with FCAS.

Study Overview

• Status: Completed
• Conditions: Familial Cold Autoinflammatory Syndrome
• Intervention / Treatment: Drug: DFV890

Detailed Description

This was an open-label, single-arm, multiple dose, phase II study to assess safety, tolerability and clinical efficacy of DFV890 in participants with FCAS who showed evidence of inflammatory activity after the cold challenge performed during screening.

The study included a screening period, a treatment period and a follow-up period.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris, France, 75970
    • Novartis Investigative Site
• Germany
  • Tuebingen, Germany, 72076
    • Novartis Investigative Site
• United States
  • California
    • La Jolla, California, United States, 92093
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Written informed consent must be obtained before any study-specific assessment is performed
• Body mass index within the range of 18-35 kg/m2
• Patients with a genetic diagnosis of FCAS
• Patients with a clinical history and investigations consistent with FCAS

Exclusion Criteria:

• Anti-rejection and/or immunomodulatory drugs must be discontinued (please, see protocol for further details)
• Clinically significant, suspected active or chronic bacterial (including Mycobacterium tuberculosis), viral or fungal infection within 30 days prior to Day 1.
• Patients with innate (e.g. TLR immunodeficiencies, defects in IFN-γ signaling) or acquired immune deficiencies (e.g. AIDS).
• Presence of human immunodeficiency virus (HIV) infection, hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (anti-HBc), or hepatitis C antibodies at screening.
• Live vaccines within 4 weeks of Day 1
• Pregnant or nursing (lactating) women.
• Women of child-bearing potential unless they are using highly effective methods of contraception.

Other protocol-defined inclusion/exclusion criteria may apply.

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: DFV890	Drug: DFV890; 100 mg of DFV890 film coated tablets twice daily (b.i.d.). for 3 days starting in the morning of Day 1 and 100 mg of DFV890 in the morning on the fourth day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ratio of Fold Change From Pre-challenge to the Highest Post-challenge Value of White Cell Count (WCC) Between Treatment and Screening Period	A cold challenge was performed during the screening period and on Day 4 of the treatment period. Fold change from pre-challenge to highest post-challenge value of WCC was defined as the ratio of the highest post-challenge WCC value to the pre-challenge WCC value. The ratio of fold change was defined as treatment fold change divided by the screen fold change. A value of less than 1 for the ratio of fold change indicates a lower relative increase of WCC in the treatment than in the screening period, which is a favorable outcome. The log-transformed fold change from pre-challenge to the highest post challenge WCC was analyzed using a log-linear mixed effect model. The analysis was carried out considering the data from -2 to 8 hrs post challenge. The unforeseen screen failure rate and recruitment challenges resulted in early closure of the study. Only 4 out of planned 6 participants were enrolled in the study; thus, the results should be interpreted cautiously.	Screening period and treatment period (Day 4): pre cold challenge and up to 8 hours post cold challenge. The duration of the cold challenge was 45 minutes.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	Number of participants with treatment emergent AEs (any AE regardless of seriousness), AEs led to study treatment discontinuation, SAEs and SAEs led to study treatment discontinuation.	Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 34 days
Physician Global Assessment of Autoinflammatory Disease Activity	The Physician global assessment of autoinflammatory disease activity is a questionnaire completed by the Investigator. It uses a 5-point scale. Lower scores represent better outcomes. 0 = Absent; = Minimal; = Mild; = Moderate; = Severe	Screening and Treatment (Day 4): 1 hour pre and 2, 3, 5, 9 and 24 hours post. Scheduled time refers to the time post-meal (screening) and to the time post-dose (treatment). The start of the cold challenge is at 1 hour post and the duration is 45 minutes.
Physician's Severity Assessment of Autoinflammatory Disease Signs and Symptoms	The Physician's severity assessment of autoinflammatory disease signs and symptoms is a questionnaire completed by the Investigator. It uses a 5-point scale. Lower scores represent better outcomes. 0 = Absent; = Minimal; = Mild; = Moderate; = Severe The following items were assessed: Assessment of skin disease (urticarial skin rash); Assessment of arthralgia; Assessment of myalgia; Assessment of headache/migraine; Assessment of conjunctivitis; Assessment of fatigue/malaise	Screening and Treatment (Day 4): 1 hour pre and 2, 3, 5, 9 and 24 hours post. Scheduled time refers to the time post-meal (screening) and to the time post-dose (treatment). The start of the cold challenge is at 1 hour post and the duration is 45 minutes.
Patient's Global Assessment of Disease Activity	Patient's global assessment of disease activity is a questionnaire completed by the patient. It uses a 5-point scale. The patient selected a rating based on the patient's current disease activity at the time of the assessment. Lower scores represent better outcomes. 0 = Absent; = Minimal; = Mild; = Moderate; = Severe	Screening and Treatment (Day 4): 1 hour pre and 2, 3, 5, 9 and 24 hours post. Scheduled time refers to the time post-meal (screening) and to the time post-dose (treatment). The start of the cold challenge is at 1 hour post and the duration is 45 minutes.

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on www.novctrd.com

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2021
• Primary Completion (Actual): December 13, 2022
• Study Completion (Actual): May 5, 2023

Study Registration Dates

• First Submitted: April 22, 2021
• First Submitted That Met QC Criteria: April 28, 2021
• First Posted (Actual): May 3, 2021

Study Record Updates

• Last Update Posted (Estimated): October 9, 2024
• Last Update Submitted That Met QC Criteria: October 7, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: CAPS; DFV890; Familial Cold Auto-inflammatory Syndrome; FCAS; NLRP3 inhibitor, inflammasome inhibition; Cryopyrin-associated periodic syndromes
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Disease Attributes; Disease; Genetic Diseases, Inborn; Hereditary Autoinflammatory Diseases; Skin Diseases, Genetic; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Chronic Disease; Chronic Inducible Urticaria; Chronic Urticaria; Cold Urticaria; Syndrome; Cryopyrin-Associated Periodic Syndromes
• Other Study ID Numbers: CDFV890A12201; 2020-005948-33 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

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