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

NCT04868968 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: CDFV890A122012020-005948-33
• Study Type: interventional
• Target: 4
• Locations: 3 countries
• Sites: 3

Brief Summary

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

Conditions

Familial Cold Autoinflammatory Syndrome

Keywords

Familial Cold Auto-inflammatory Syndrome; FCAS; DFV890; NLRP3 inhibitor, inflammasome inhibition; Cryopyrin-associated periodic syndromes; CAPS

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

  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

  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

  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

  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.

Study Arms (1)

DFV890

EXPERIMENTAL

DFV890

Drug: DFV890

Interventions

DFV890 DRUG

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.

DFV890

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (3)

Novartis Investigative Site

La Jolla, California, 92093, United States

Location

Novartis Investigative Site

Paris, 75970, France

Location

Novartis Investigative Site

Tübingen, 72076, Germany

Location

Related Links

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

MeSH Terms

Conditions

Cryopyrin-Associated Periodic Syndromes

Condition Hierarchy (Ancestors)

Hereditary Autoinflammatory Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Skin Diseases; Skin and Connective Tissue Diseases; Chronic Inducible Urticaria; Chronic Urticaria; Urticaria; Skin Diseases, Vascular; Cold Urticaria; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

+1 862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2021
• First Posted: May 3, 2021
• Study Start: September 20, 2021
• Primary Completion: December 13, 2022
• Study Completion: May 5, 2023
• Last Updated: October 9, 2024
• Results First Posted: May 3, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share

Locations

DE (1); US (1); FR (1)