Trial Outcomes & Findings for Study of Efficacy, Safety and Tolerability of DFV890 in Patients With Knee Osteoarthritis (NCT NCT04886258)

NCT ID: NCT04886258

Last Updated: 2026-01-28

Results Overview

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).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 115 participants
• Primary outcome timeframe: Baseline, Week 12
• Results posted on: 2026-01-28

Participant Flow

Participants took part in 32 investigative sites in 8 countries.

The study consisted of a screening period up to 45 days.

Participant milestones

Measure	DFV890 DFV890 was administered orally twice per day, 10 mg during 2 weeks and 25 mg during the next 10 weeks.	Placebo Matching Placebo was administered orally twice per day during 12 weeks.
Overall Study STARTED	58	57
Overall Study COMPLETED	52	54
Overall Study NOT COMPLETED	6	3

Reasons for withdrawal

Measure	DFV890 DFV890 was administered orally twice per day, 10 mg during 2 weeks and 25 mg during the next 10 weeks.	Placebo Matching Placebo was administered orally twice per day during 12 weeks.
Overall Study Adverse Event	1	0
Overall Study Withdrawal by Subject	5	3

Baseline Characteristics

Study of Efficacy, Safety and Tolerability of DFV890 in Patients With Knee Osteoarthritis

Baseline characteristics by cohort

Measure	DFV890 n=58 Participants DFV890 was administered orally twice per day, 10 mg during 2 weeks and 25 mg during the next 10 weeks.	Placebo n=57 Participants Matching Placebo was administered orally twice per day during 12 weeks.	Total n=115 Participants Total of all reporting groups
Age, Continuous	63.9 years STANDARD_DEVIATION 7.00 • n=158 Participants	64.3 years STANDARD_DEVIATION 7.32 • n=157 Participants	64.1 years STANDARD_DEVIATION 7.13 • n=315 Participants
Sex: Female, Male Female	45 Participants n=158 Participants	48 Participants n=157 Participants	93 Participants n=315 Participants
Sex: Female, Male Male	13 Participants n=158 Participants	9 Participants n=157 Participants	22 Participants n=315 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=158 Participants	1 Participants n=157 Participants	1 Participants n=315 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=158 Participants	3 Participants n=157 Participants	4 Participants n=315 Participants
Race/Ethnicity, Customized White	57 Participants n=158 Participants	51 Participants n=157 Participants	108 Participants n=315 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=158 Participants	2 Participants n=157 Participants	2 Participants n=315 Participants

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: Full analysis set: All randomized participants that have received any study drug and had a valid measurement at the respective time-point. Based on a primary estimand framework.

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).

Outcome measures

Measure	DFV890 n=45 Participants DFV890 was administered orally twice per day, 10 mg during 2 weeks and 25 mg during the next 10 weeks.	Placebo n=41 Participants Matching Placebo was administered orally twice per day during 12 weeks.
Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale	21.7 score on scale Standard Error 2.52	16.7 score on scale Standard Error 2.61

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Full analysis set: All randomized participants that have received any study drug and had a valid measurement at the respective time-point. Based on a secondary estimand framework.

Magnetic resonance images (MRI) were obtained from the target knee with dynamic contrast enhancement (DCE) to visualize and quantify changes in k-trans as a marker of the activity of synovial inflammation. In dynamic contrast-enhanced MRI, ktrans is a parameter that reflects how quickly contrast agent moves from blood vessels into the surrounding tissue, capturing both blood flow and vascular permeability. In synovitis, inflamed synovial tissue shows increased perfusion and leaky microvasculature, so higher k-trans values are interpreted as indicating more active synovial inflammation. Change from baseline in synovitis activity level measured from ktrans was analyzed to compare treatment groups. The model included treatment as fixed effect and baseline as continuous covariate. Ktrans is a marker of synovial inflammation in relation to vascularity permeability.

Outcome measures

Measure	DFV890 n=39 Participants DFV890 was administered orally twice per day, 10 mg during 2 weeks and 25 mg during the next 10 weeks.	Placebo n=35 Participants Matching Placebo was administered orally twice per day during 12 weeks.
Change From Baseline in Synovitis Activity Level Measured From Ktrans by Dynamic Contrast Enhanced MRI (DCE-MRI)	-0.0029 min^-1 Standard Error 0.0013	-0.0003 min^-1 Standard Error 0.0014

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8 and 12

Population: Full analysis set: All randomized participants that have received any study drug and had a valid measurement at the respective time-point.

HsCRP is a protein produced by the liver in response to inflammation in the body, such as from an infection, injury, or chronic inflammatory conditions. HsCRP was used to assess the effect of DFV890 compared to placebo on systemic inflammatory status.

Outcome measures

Measure	DFV890 n=56 Participants DFV890 was administered orally twice per day, 10 mg during 2 weeks and 25 mg during the next 10 weeks.	Placebo n=57 Participants Matching Placebo was administered orally twice per day during 12 weeks.
Change From Baseline in Serum High Sensitivity C-reactive Protein (hsCRP) Level Week 2	-1.753 mg/L Standard Deviation 3.3198	0.486 mg/L Standard Deviation 2.8528
Change From Baseline in Serum High Sensitivity C-reactive Protein (hsCRP) Level Week 4	-1.783 mg/L Standard Deviation 3.9239	0.541 mg/L Standard Deviation 4.6472
Change From Baseline in Serum High Sensitivity C-reactive Protein (hsCRP) Level Week 8	-1.953 mg/L Standard Deviation 2.3093	-0.045 mg/L Standard Deviation 2.1858
Change From Baseline in Serum High Sensitivity C-reactive Protein (hsCRP) Level Week 12	-0.855 mg/L Standard Deviation 7.7378	1.119 mg/L Standard Deviation 5.0495

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8 and 12

Population: Full analysis set: All randomized participants that have received any study drug and had a valid measurement at the respective time-point.

ANC measures the number of neutrophils, a type of white blood cell crucial for fighting infection, in a blood sample. ANC was used to judge target engagement of DFV890.

Outcome measures

Measure	DFV890 n=52 Participants DFV890 was administered orally twice per day, 10 mg during 2 weeks and 25 mg during the next 10 weeks.	Placebo n=56 Participants Matching Placebo was administered orally twice per day during 12 weeks.
Change From Baseline in Absolute Neutrophil Counts (ANC) Week 2	-0.981 neutrophils*10^9/L Standard Deviation 1.4694	-0.221 neutrophils*10^9/L Standard Deviation 0.7925
Change From Baseline in Absolute Neutrophil Counts (ANC) Week 4	-0.980 neutrophils*10^9/L Standard Deviation 1.4698	-0.054 neutrophils*10^9/L Standard Deviation 0.8272
Change From Baseline in Absolute Neutrophil Counts (ANC) Week 8	-1.045 neutrophils*10^9/L Standard Deviation 1.2502	-0.056 neutrophils*10^9/L Standard Deviation 1.1135
Change From Baseline in Absolute Neutrophil Counts (ANC) Week 12	-1.030 neutrophils*10^9/L Standard Deviation 1.0915	-0.167 neutrophils*10^9/L Standard Deviation 0.8977

SECONDARY outcome

Timeframe: Week 2 and Week 12: pre-dose, 1h, 3h, 5h, 8h

Population: The Pharmacokinetic (PK) analysis set included all participants with at least 1 available valid (i.e., not flagged for exclusion) PK concentration measurement, who received DFV890 and with no protocol deviations that impact on PK data.

Cmax is defined as the maximum (peak) observed concentration following a dose. DFV890 plasma concentrations were determined using the actual recorded sampling times and non-compartmental method with Phoenix WinNonlin (Version 8). DFV890 was determined by a validated LC-MS/MS method; the lower limit of quantification (LLOQ) is 1 ng/mL.

Outcome measures

Measure	DFV890 n=52 Participants DFV890 was administered orally twice per day, 10 mg during 2 weeks and 25 mg during the next 10 weeks.	Placebo Matching Placebo was administered orally twice per day during 12 weeks.
Maximum Plasma Concentration (Cmax) of DFV890 Week 2	1550 ng/mL Standard Deviation 603	—
Maximum Plasma Concentration (Cmax) of DFV890 Week 12	3240 ng/mL Standard Deviation 916	—

SECONDARY outcome

Timeframe: Week 2 and Week 12: pre-dose, 1h, 3h, 5h, 8h

Population: The PK analysis set included all participants with at least 1 available valid (i.e., not flagged for exclusion) PK concentration measurement, who received DFV890 and with no protocol deviations that impact on PK data.

AUClast is the area under the plasma concentration-time curve from time zero to the time of last quantifiable concentration (tlast). DFV890 plasma concentrations were determined using the actual recorded sampling times and non-compartmental method with Phoenix WinNonlin (Version 8). DFV890 was determined by a validated LC-MS/MS method; the lower limit of quantification (LLOQ) is 1 ng/mL.

Outcome measures

Measure	DFV890 n=52 Participants DFV890 was administered orally twice per day, 10 mg during 2 weeks and 25 mg during the next 10 weeks.	Placebo Matching Placebo was administered orally twice per day during 12 weeks.
Area Under Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of DFV890 Week 2	9070 h*ng/mL Standard Deviation 3940	—
Area Under Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of DFV890 Week 12	19300 h*ng/mL Standard Deviation 6370	—

SECONDARY outcome

Timeframe: Week 2 and Week 12: pre-dose, 1h, 3h, 5h, 8h

Population: The PK analysis set included all participants with at least 1 available valid (i.e., not flagged for exclusion) PK concentration measurement, who received DFV890 and with no protocol deviations that impact on PK data.

AUC(0-12h) is the area under the plasma concentration-time curve from time zero to 12 hours. To calculate AUC0-12h (corresponding to AUCtau, or AUC within a dosing interval), the concentration at 0 hours was used also as a 12 hours time point or, if not feasible, AUC0-12h was extrapolated. DFV890 plasma concentrations were determined using the actual recorded sampling times and non-compartmental method with Phoenix WinNonlin (Version 8). DFV890 was determined by a validated LC-MS/MS method; the lower limit of quantification (LLOQ) is 1 ng/mL.

Outcome measures

Measure	DFV890 n=47 Participants DFV890 was administered orally twice per day, 10 mg during 2 weeks and 25 mg during the next 10 weeks.	Placebo Matching Placebo was administered orally twice per day during 12 weeks.
Area Under Plasma Concentration-time Curve From Time Zero to 12 Hours (AUC0-12h) of DFV890 Week 2	12300 h*ng/mL Standard Deviation 5120	—
Area Under Plasma Concentration-time Curve From Time Zero to 12 Hours (AUC0-12h) of DFV890 Week 12	26700 h*ng/mL Standard Deviation 8210	—

SECONDARY outcome

Timeframe: Week 2 and Week 12: pre-dose

Population: The PK analysis set included all participants with at least 1 available valid (i.e., not flagged for exclusion) PK concentration measurement, who received DFV890 and with no protocol deviations that impact on PK data.

DFV890 plasma concentrations were determined using the actual recorded sampling times and non-compartmental method with Phoenix WinNonlin (Version 8). DFV890 was determined by a validated LC-MS/MS method; the anticipated lower limit of quantification (LLOQ) is 1 ng/mL.

Outcome measures

Measure	DFV890 n=55 Participants DFV890 was administered orally twice per day, 10 mg during 2 weeks and 25 mg during the next 10 weeks.	Placebo Matching Placebo was administered orally twice per day during 12 weeks.
Pre-dose Trough Concentration (Ctrough) of DFV890 Week 2	653 ng/mL Standard Deviation 360	—
Pre-dose Trough Concentration (Ctrough) of DFV890 Week 12	1530 ng/mL Standard Deviation 665	—

SECONDARY outcome

Timeframe: Baseline, Week 2, 4, 8 and 12

Population: Full analysis set: All randomized participants that have received any study drug and had a valid measurement at the respective time-point. Based on a secondary estimand framework.

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 other symptoms (eg., stiffness, swelling, clicking) consisting of 7 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 symptoms and 0 indicating extreme symptoms) is calculated for each subscale. Change from baseline in other symptoms score was analyzed using a 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).

Outcome measures

Measure	DFV890 n=47 Participants DFV890 was administered orally twice per day, 10 mg during 2 weeks and 25 mg during the next 10 weeks.	Placebo n=43 Participants Matching Placebo was administered orally twice per day during 12 weeks.
Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Other Symptoms Subscale Week 2	6.9 score on scale Standard Error 1.94	2.0 score on scale Standard Error 2.09
Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Other Symptoms Subscale Week 4	12.3 score on scale Standard Error 2.25	8.1 score on scale Standard Error 2.31
Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Other Symptoms Subscale Week 8	16.2 score on scale Standard Error 2.55	12.6 score on scale Standard Error 2.59
Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Other Symptoms Subscale Week 12	19.3 score on scale Standard Error 2.57	13.8 score on scale Standard Error 2.67

SECONDARY outcome

Timeframe: Baseline, Week 2, 4, 8 and 12

Population: Full analysis set: All randomized participants that have received any study drug and had a valid measurement at the respective time-point. Based on a secondary estimand framework.

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 Function in Daily Living consisting of 17 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 impact on function in daily living and 0 indicating extreme impact on function in daily living) is calculated for each subscale. Change from baseline in KOOS daily living function score was analyzed using a 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).

Outcome measures

Measure	DFV890 n=47 Participants DFV890 was administered orally twice per day, 10 mg during 2 weeks and 25 mg during the next 10 weeks.	Placebo n=43 Participants Matching Placebo was administered orally twice per day during 12 weeks.
Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Function in Daily Living Subscale Week 2	5.7 score on scale Standard Error 1.71	6.9 score on scale Standard Error 1.85
Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Function in Daily Living Subscale Week 4	12.7 score on scale Standard Error 1.92	12.0 score on scale Standard Error 1.98
Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Function in Daily Living Subscale Week 8	17.2 score on scale Standard Error 2.40	15.8 score on scale Standard Error 2.46
Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Function in Daily Living Subscale Week 12	21.1 score on scale Standard Error 2.46	19.4 score on scale Standard Error 2.57

SECONDARY outcome

Timeframe: Baseline, Week 2, 4, 8 and 12

Population: Full analysis set: All randomized participants that have received any study drug and had a valid measurement at the respective time-point. Based on a secondary estimand framework.

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 function in sport and recreation consisting of 5 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 impact on sport and recreation and 0 indicating extreme impact on sport and recreation) is calculated for each subscale. Change from baseline in function in sport and recreation score was analyzed using a 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).

Outcome measures

Measure	DFV890 n=47 Participants DFV890 was administered orally twice per day, 10 mg during 2 weeks and 25 mg during the next 10 weeks.	Placebo n=43 Participants Matching Placebo was administered orally twice per day during 12 weeks.
Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Function in Sport and Recreation Subscale Week 2	3.1 score on scale Standard Error 2.40	7.5 score on scale Standard Error 2.60
Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Function in Sport and Recreation Subscale Week 4	11.8 score on scale Standard Error 2.71	10.7 score on scale Standard Error 2.79
Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Function in Sport and Recreation Subscale Week 8	17.7 score on scale Standard Error 3.37	14.4 score on scale Standard Error 3.43
Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Function in Sport and Recreation Subscale Week 12	16.6 score on scale Standard Error 3.30	19.3 score on scale Standard Error 3.41

SECONDARY outcome

Timeframe: Baseline, Week 2, 4, 8 and 12

Population: Full analysis set: All randomized participants that have received any study drug and had a valid measurement at the respective time-point. Based on a secondary estimand framework.

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 knee-related quality of life consisting of 4 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 impact on knee-related quality of life and 0 indicating extreme impact on knee-related quality of life) is calculated for each subscale. Change from baseline in knee related quality of life score was analyzed using a 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).

Outcome measures

Measure	DFV890 n=47 Participants DFV890 was administered orally twice per day, 10 mg during 2 weeks and 25 mg during the next 10 weeks.	Placebo n=43 Participants Matching Placebo was administered orally twice per day during 12 weeks.
Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Knee-related Quality of Life (QOL) Subscale Week 2	5.0 score on scale Standard Error 1.80	6.3 score on scale Standard Error 1.93
Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Knee-related Quality of Life (QOL) Subscale Week 4	13.2 score on scale Standard Error 2.19	11.7 score on scale Standard Error 2.26
Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Knee-related Quality of Life (QOL) Subscale Week 8	17.1 score on scale Standard Error 2.54	13.2 score on scale Standard Error 2.58
Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Knee-related Quality of Life (QOL) Subscale Week 12	18.4 score on scale Standard Error 2.65	16.3 score on scale Standard Error 2.75

SECONDARY outcome

Timeframe: Baseline, Week 2, 4, 8

Population: Full analysis set: All randomized participants that have received any study drug and had a valid measurement at the respective time-point. Based on a secondary estimand framework.

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 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 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).

Outcome measures

Measure	DFV890 n=47 Participants DFV890 was administered orally twice per day, 10 mg during 2 weeks and 25 mg during the next 10 weeks.	Placebo n=43 Participants Matching Placebo was administered orally twice per day during 12 weeks.
Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale Week 2	7.8 score on scale Standard Error 1.78	6.9 score on scale Standard Error 1.92
Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale Week 4	14.8 score on scale Standard Error 1.92	11.4 score on scale Standard Error 1.98
Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale Week 8	19 score on scale Standard Error 2.47	13.3 score on scale Standard Error 2.51

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8 and 12

Population: Full analysis set: All randomized participants that have received any study drug and had a valid measurement at the respective time-point. Based on a secondary estimand framework.

The Numerical Rating Scale (NRS) Pain is a subjective assessment in which individuals rate their pain on an eleven-point numerical scale. NRS pain score ranges from 0-10 and for analyses were transformed to a 0-100 scale to be consistent with KOOS pain scores. A negative change from baseline implied improvement in pain. The NRS Pain instrument had a recall period of 24 hours and the participants were asked to rate the pain intensity at its worst. Change from baseline in NRS pain score was analyzed using a 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).

Outcome measures

Measure	DFV890 n=47 Participants DFV890 was administered orally twice per day, 10 mg during 2 weeks and 25 mg during the next 10 weeks.	Placebo n=43 Participants Matching Placebo was administered orally twice per day during 12 weeks.
Change From Baseline in Numeric Rating Scale (NRS) for Pain Week 2	-10.5 score on scale Standard Error 2.43	-11.5 score on scale Standard Error 2.6
Change From Baseline in Numeric Rating Scale (NRS) for Pain Week 4	-18.1 score on scale Standard Error 2.65	-14.4 score on scale Standard Error 2.74
Change From Baseline in Numeric Rating Scale (NRS) for Pain Week 8	-27.2 score on scale Standard Error 2.86	-18.8 score on scale Standard Error 2.92
Change From Baseline in Numeric Rating Scale (NRS) for Pain Week 12	-29.7 score on scale Standard Error 3.07	-23.9 score on scale Standard Error 3.19

POST_HOC outcome

Timeframe: Baseline, Week 2, Week 4, Week 8, Week 12, End of Study (up to approximately 14 weeks)

Population: Safety analysis set: All randomized participants that have received any study drug and had a valid measurement at the respective time-point.

Neutrophils, a type of white blood cell essential for fighting infection, are measured in blood samples. Instances of neutrophil counts falling below the lower limit of normal were not consistently reported by all Principal Investigators as Adverse Events. To address this, an ad-hoc outcome measure was introduced to capture 'Neutrophil counts below the lower limit' based on laboratory data.

Outcome measures

Measure	DFV890 n=58 Participants DFV890 was administered orally twice per day, 10 mg during 2 weeks and 25 mg during the next 10 weeks.	Placebo n=57 Participants Matching Placebo was administered orally twice per day during 12 weeks.
Number of Participants With Neutrophil Counts <2.03 x 10⁹/l (Lower Limit of Normal) Week 2	11 Participants	1 Participants
Number of Participants With Neutrophil Counts <2.03 x 10⁹/l (Lower Limit of Normal) Week 4	12 Participants	1 Participants
Number of Participants With Neutrophil Counts <2.03 x 10⁹/l (Lower Limit of Normal) Baseline	3 Participants	1 Participants
Number of Participants With Neutrophil Counts <2.03 x 10⁹/l (Lower Limit of Normal) Week 8	9 Participants	0 Participants
Number of Participants With Neutrophil Counts <2.03 x 10⁹/l (Lower Limit of Normal) Week 12	15 Participants	2 Participants
Number of Participants With Neutrophil Counts <2.03 x 10⁹/l (Lower Limit of Normal) End of Study	2 Participants	3 Participants

Adverse Events

DFV890 10mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

DFV890 25mg

Serious events: 1 serious events

Other events: 19 other events

Deaths: 0 deaths

DFV890

Serious events: 1 serious events

Other events: 20 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Total

Serious events: 2 serious events

Other events: 31 other events

Deaths: 0 deaths

Serious adverse events

Measure	DFV890 10mg n=58 participants at risk DFV890 was administered orally twice per day, 10 mg during 2 weeks. AEs that started while on DFV890 10 mg (week 1 and 2).	DFV890 25mg n=58 participants at risk DFV890 was administered orally twice per day, 10 mg during 2 weeks and 25 mg during the next 10 weeks. AEs that started while on DFV890 25 mg (weeks 3 to 12 + 30 days follow up).	DFV890 n=58 participants at risk DFV890 was administered orally twice per day, 10 mg during 2 weeks and 25 mg during the next 10 weeks.	Placebo n=57 participants at risk Matching Placebo was administered orally twice per day during 12 weeks.	Total n=115 participants at risk Total
Cardiac disorders Atrial fibrillation	0.00% 0/58 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.	0.00% 0/58 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.	0.00% 0/58 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.	1.8% 1/57 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.	0.87% 1/115 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.
Gastrointestinal disorders Inguinal hernia	0.00% 0/58 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.	1.7% 1/58 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.	1.7% 1/58 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.	0.00% 0/57 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.	0.87% 1/115 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.00% 0/58 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.	1.7% 1/58 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.	1.7% 1/58 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.	0.00% 0/57 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.	0.87% 1/115 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.

Other adverse events

Measure	DFV890 10mg n=58 participants at risk DFV890 was administered orally twice per day, 10 mg during 2 weeks. AEs that started while on DFV890 10 mg (week 1 and 2).	DFV890 25mg n=58 participants at risk DFV890 was administered orally twice per day, 10 mg during 2 weeks and 25 mg during the next 10 weeks. AEs that started while on DFV890 25 mg (weeks 3 to 12 + 30 days follow up).	DFV890 n=58 participants at risk DFV890 was administered orally twice per day, 10 mg during 2 weeks and 25 mg during the next 10 weeks.	Placebo n=57 participants at risk Matching Placebo was administered orally twice per day during 12 weeks.	Total n=115 participants at risk Total
Gastrointestinal disorders Diarrhoea	1.7% 1/58 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.	1.7% 1/58 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.	3.4% 2/58 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.	5.3% 3/57 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.	4.3% 5/115 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.
Infections and infestations COVID-19	0.00% 0/58 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.	8.6% 5/58 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.	8.6% 5/58 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.	3.5% 2/57 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.	6.1% 7/115 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.
Infections and infestations Nasopharyngitis	1.7% 1/58 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.	5.2% 3/58 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.	5.2% 3/58 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.	7.0% 4/57 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.	6.1% 7/115 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.
Investigations Neutrophil count decreased	0.00% 0/58 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.	17.2% 10/58 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.	17.2% 10/58 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.	3.5% 2/57 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.	10.4% 12/115 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.
Nervous system disorders Headache	1.7% 1/58 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.	5.2% 3/58 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.	6.9% 4/58 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.	5.3% 3/57 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.	6.1% 7/115 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 114 days.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: + 1 862 778 8300

Email: novartis.email@novartis.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER