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| ID | Type | Description | Link |
|---|---|---|---|
| 2020-005948-33 | EudraCT Number |
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The purpose of this phase II study was to assess the safety, tolerability and efficacy of DFV890 in participants with FCAS.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| DFV890 | Experimental | DFV890 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
|
| 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. |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
Other protocol-defined inclusion/exclusion criteria may apply.
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | La Jolla | California | 92093 | United States | ||
| Novartis Investigative Site |
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| Label | URL |
|---|---|
| A Plain Language Trial Summary is available on www.novctrd.com | View source |
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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
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During the screening period the participant's eligibility was assessed at a screening visit and a screening cold challenge was performed.
Participants took part in 3 investigative sites in 3 countries.
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| ID | Title | Description |
|---|---|---|
| FG000 | DFV890 100mg - Treatment | DFV890 100mg oral dose, twice daily for 3 days and one last dose in the morning of Day 4 of the treatment period |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | DFV890 100mg - Treatment | DFV890 100mg oral dose, twice daily for 3 days and one last dose in the morning of Day 4 of the treatment period |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | The Pharmacodynamic (PD) analysis set included all participants with no protocol deviations with relevant impact on PD data. | Posted | Geometric Least Squares Mean | 90% Confidence Interval | ratio of fold change | 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. |
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
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | DFV890 100 mg - Treatment | DFV890 100mg oral dose, twice daily for 3 days and one last dose in the morning of Day 4 of the treatment period |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Asthenia | General disorders | MedDRA (26.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | +1 862-778-8300 | novartis.email@novartis.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 19, 2022 | Mar 11, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 17, 2023 | Mar 11, 2024 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D056587 | Cryopyrin-Associated Periodic Syndromes |
| ID | Term |
|---|---|
| D056660 | Hereditary Autoinflammatory Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D012873 | Skin Diseases, Genetic |
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| 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
| 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
The following items were assessed:
| 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
| 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. |
| Paris |
| 75970 |
| France |
| Novartis Investigative Site | Tübingen | 72076 | Germany |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
|
|
|
| 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. | The safety analysis set included all participants that received any study drug. | Posted | Count of Participants | Participants | 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
| The Pharmacodynamic (PD) analysis set included all participants with no protocol deviations with relevant impact on PD data. | Posted | Count of Participants | Participants | 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
The following items were assessed:
| The Pharmacodynamic (PD) analysis set included all participants with no protocol deviations with relevant impact on PD data. | Posted | Count of Participants | Participants | 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
| The Pharmacodynamic (PD) analysis set included all participants with no protocol deviations with relevant impact on PD data. | Posted | Count of Participants | Participants | 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. |
|
|
|
| 0 |
| 4 |
| 0 |
| 4 |
| 4 |
| 4 |
| Chills | General disorders | MedDRA (26.0) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (26.0) | Systematic Assessment |
|
| Conjunctivitis | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (26.0) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (26.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (26.0) | Systematic Assessment |
|
| Cold urticaria | Skin and subcutaneous tissue disorders | MedDRA (26.0) | Systematic Assessment |
|
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA (26.0) | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (26.0) | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA (26.0) | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (26.0) | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D000094482 | Chronic Inducible Urticaria |
| D000080223 | Chronic Urticaria |
| D014581 | Urticaria |
| D017445 | Skin Diseases, Vascular |
| D000096703 | Cold Urticaria |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Title | Measurements |
|---|---|
|
| SAE leading to discontinuation |
|
| Mild |
|
| Moderate |
|
| Severe |
|
| 2 hours post |
|
| 3 hours post |
|
| 5 hours post |
|
| 9 hours post |
|
| 24 hours post |
|
| Mild |
|
| Moderate |
|
| Severe |
|
| Arthralgia 2 hours post |
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| Arthralgia 3 hours post |
|
| Arthralgia 5 hours post |
|
| Arthralgia 9 hours post |
|
| Arthralgia 24 hours post |
|
| Conjunctivitis 1 hour pre |
|
| Conjunctivitis 2 hours post |
|
| Conjunctivitis 3 hours post |
|
| Conjunctivitis 5 hours post |
|
| Conjunctivitis 9 hours post |
|
| Conjunctivitis 24 hours post |
|
| Fatigue/Malaise 1 hour pre |
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| Fatigue/Malaise 2 hours post |
|
| Fatigue/Malaise 3 hours post |
|
| Fatigue/Malaise 5 hours post |
|
| Fatigue/Malaise 9 hours post |
|
| Fatigue/Malaise 24 hours post |
|
| Headache/Migraine 1 hour pre |
|
| Headache/Migraine 2 hours post |
|
| Headache/Migraine 3 hours post |
|
| Headache/Migraine 5 hours post |
|
| Headache/Migraine 9 hours post |
|
| Headache/Migraine 24 hours post |
|
| Myalgia 1 hour pre |
|
| Myalgia 2 hours post |
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| Myalgia 3 hours post |
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| Myalgia 5 hours post |
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| Myalgia 9 hours post |
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| Myalgia 24 hours post |
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| Skin disease 1 hour pre |
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| Skin disease 2 hours post |
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| Skin disease 3 hours post |
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| Skin disease 5 hours post |
|
| Skin disease 9 hours post |
|
| Skin disease 24 hours post |
|
| Mild |
|
| Moderate |
|
| Severe |
|
| 2 hours post |
|
| 3 hours post |
|
| 5 hours post |
|
| 9 hours post |
|
| 24 hours post |
|