Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
DFV890 · 5 trials · 5 indications
Serum levels of IL-6 at 3 weeks after the start of a dosing period for DFV890. The circulating serum levels of the cytokine IL-6 were measured by a validated enzyme-linked immunosorbent assay (ELISA) assay at a qualified vendor.The Emax model selected for IL-6 analysis was a model with 2 covariates (IL-6 baseline and bodyweight) and 1 random effect.
Serum levels of IL-18 at 3 weeks after the start of a dosing period for DFV890. The circulating serum levels of the cytokine IL-18 were measured by a validated enzyme-linked immunosorbent assay (ELISA) assay at a qualified vendor.The Emax model selected for IL-18 analysis was a model with 2 covariates (IL-18 baseline and bodyweight) and 1 random effect.
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 KOOS questionnaire is a commonly used instrument to assess the patient's perception about their knee and associated problems. The original KOOS consists of 5 subscales. One of those is the pain frequency/severity during functional activities consisting of 9 questions with a recall of 7 days. Each question has 5 standardized answer options with a score from 0 to 4. A normalized score (100 indicating no pain and 0 indicating extreme pain) is calculated for each subscale. Change from baseline in KOOS pain score was analyzed using a mixed effects model for repeated measures (MMRM) including all time-points to compare treatment groups. The model includes baseline, treatment, timepoint, baseline-by-timepoints interaction and treatment-by-timepoints interaction as fixed effects. Missing data is assumed to be Missing at Random (MAR).
The APACHE II ("Acute Physiology And Chronic Health Evaluation II") is a severity-of-disease classification system. An integer score from 0 to 71 is computed based on several measurements; higher scores correspond to more severe disease and a higher risk of death. In practice, it is rare for any participant to accumulate more than 55 points. APACHE II score was measured on Day 15 or on the day of discharge (whichever was earlier). Participants who died on Day 15 or earlier were assigned the highest observed APACHE II score of any of the participants at any time during the trial (worst case imputation for deaths). Missing data values of the parameters required for the derivation of the APACHE II score were replaced by the last available assessment.
A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as clinically relevant, occurring during the DLT monitoring period following the first administration of study treatment.
Incidence and severity of AEs and SAEs by treatment group, including changes in vital signs, electrocardiograms (ECGs) and laboratory values qualifying and reported as AEs.
Number of patients with dose adjustments (interruptions, discontinuations and reductions) summarized by treatment group.
| Arm | Type | Description |
|---|---|---|
| Treatment Sequence 1 | EXPERIMENTAL | On Day 1, participants received 1 tablet of DFV890 matching placebo QD. Participants continued receiving DFV890 oral placebo QD until Day 22 when they started receiving DFV890 10 mg QD. The dose of DFV890 was uptitrated to 25 mg on Day 43 and to 100 mg on Day 64. |
| Treatment sequence 2 | EXPERIMENTAL | On Day 1, participants received 1 tablet of DFV890 matching placebo QD. Participants continued receiving DFV890 oral placebo QD until Day 22 when they started receiving DFV890 25 mg QD. The dose of DFV890 was uptitrated to 50 mg on Day 43 and to 100 mg on Day 64. |
| Treatment sequence 3 | EXPERIMENTAL | On Day 1, participants received 1 tablet of DFV890 10 mg QD. Participants continued receiving DFV890 10 mg QD until Day 22 when they started receiving DFV890 25 mg QD. The dose of DFV890 was uptitrated to 50 mg on Day 43 and to 100 mg on Day 64. |
| Treatment sequence 4 | PLACEBO_COMPARATOR | On Day 1, participants received 1 tablet of DFV890 matching placebo QD. Participants continued receiving DFV890 oral placebo QD until Day 84. |
| DFV890 | EXPERIMENTAL | DFV890 |
| Placebo | PLACEBO_COMPARATOR | Matching Placebo was administered orally twice per day during 12 weeks. |
| DFV890 + SoC | EXPERIMENTAL | DFV890 50 mg was administered orally or nasogastrically twice per day (b.i.d) approximately 12 hours apart (morning and evening) for 14 days in addition to SoC. |
| Standard of Care (SoC) | ACTIVE_COMPARATOR | SoC was used as an active comparator arm. |
| Dose escalation: DFV890 low dose | EXPERIMENTAL | DFV890 given as single agent at a low dose |
| Dose escalation: DFV890 high dose | EXPERIMENTAL | DFV890 given as single agent at a high dose |
| Dose expansion: DFV890 low dose | EXPERIMENTAL | DFV890 given as single agent at a low dose |
| Name | Type | Description |
|---|---|---|
| DFV890 | DRUG | Oral film-coated tablets of DFV890 once daily |
| DFV890 Placebo | DRUG | Oral film-coated tablets of DFV890 placebo once daily |
| Placebo | DRUG | Matching Placebo was administered orally twice per day during 12 weeks. |
| Standard of Care (SoC) | DRUG | SoC included a variety of supportive therapies that ranged from the administration of supplementary oxygen to full intensive care support, alongside the use of antiviral treatment, convalescent plasma, corticosteroids, antibiotics or other agents. |
Inclusion Criteria: * Male and female participants aged between 18 - 85 years (inclusive) at the start of screening will be included. * Subjects must have a body mass index (BMI) within the range of 18 - 45 kg/m2. BMI = Body weight (kg) / \[Height (m)\]2 * Documented spontaneous myocardial infarcti...
DFV890 is an investigational small molecule developed by Novartis AG (ticker NVS). It is being studied across several conditions, including COVID-19 pneumonia, impaired respiratory function, coronary heart disease, familial cold autoinflammatory syndrome, myeloid diseases, and symptomatic knee osteoarthritis. It remains in clinical development and is not described as approved.
DFV890 is developed by Novartis AG, which trades under the ticker NVS. Novartis is the sponsor of the clinical studies evaluating the drug across inflammatory, respiratory, cardiovascular, and myeloid conditions.
DFV890 is in Phase 2 development. Its clinical program includes Phase 2 studies in coronary heart disease, symptomatic knee osteoarthritis, and familial cold autoinflammatory syndrome, plus a Phase 1 dose optimization and expansion study in myeloid diseases. It is investigational and not described as approved.
DFV890 has been studied in NCT06031844 for coronary heart disease with elevated hsCRP, NCT05552469 for myeloid diseases, NCT04886258 for symptomatic knee osteoarthritis, and NCT04868968 for familial cold autoinflammatory syndrome. These studies enrolled participants across the United States, Canada, Europe, and Asia.
DFV890 was evaluated in a Phase 2 study, NCT04886258, in adults with symptomatic knee osteoarthritis. That trial enrolled 115 participants aged 50 years and older across the United States, Argentina, Czechia, Germany, Hungary, Romania, Slovakia, and Spain, and it has completed. DFV890 is investigational, not an approved treatment.
DFV890 was studied in a Phase 2 trial, NCT04868968, in adults with familial cold autoinflammatory syndrome, also known as FCAS. The completed study enrolled four participants in the United States, France, and Germany. DFV890 is investigational and has not been described as approved for this condition.