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

Familial Cold Autoinflammatory Syndrome Clinical Trial

— DFV890-FCAS  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04868968
• Other study ID #: CDFV890A12201
• Secondary ID: 2020-005948-33
• Status: Completed
• Phase: Phase 2
• Start date: September 20, 2021
• Est. completion date: May 5, 2023

Study information

• Verified date: April 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4
• Est. completion date: May 5, 2023
• Est. primary completion date: December 13, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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-? 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.

Related Conditions & MeSH terms

• Cryopyrin-Associated Periodic Syndromes
• Familial Cold Autoinflammatory Syndrome
• Syndrome

Intervention

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.

Locations

Country	Name	City	State
France	Novartis Investigative Site	Paris
Germany	Novartis Investigative Site	Tuebingen
United States	Novartis Investigative Site	La Jolla	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  France,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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.
Secondary	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.
Secondary	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.