Psoriatic Arthritis
Conditions
Keywords
Placebo-Controlled, Double-blind, Multiple-dose study
Brief summary
This study is designed to evaluate the efficacy, safety, and tolerability of NDI-034858 in participants with active Psoriatic Arthritis (PsA).
Detailed description
This is a Phase 2b, Randomized, Multi-center, Double-Blind, Placebo-Controlled, Multiple Dose Study. Randomization to one of the treatments with NDI-034858 Dose 1, 2, 3 or placebo once daily (QD) will be based on a 1:1:1:1 scheme. The maximum study duration per participant is approximately 20 weeks, including up to 30 days for the screening period, a 12-week treatment period, and a 4-week safety follow-up period. Efficacy will be assessed using the ACR20 composite measure (including tender and swollen joint count, patient assessment of PsA pain visual analog scale (VAS), patient global PsA assessment VAS, physician global PsA assessment, HAQ-DI, and hsCRP) as well as the additional components. Efficacy for psoriasis among participants who have ≥ 3% BSA) involvement on Day 1, will be measured using PASI, PGAs, and BSA. Safety will be assessed by collecting AEs, recording vital signs, performing physical examinations, and evaluating clinical laboratory and ECGs results. Blood samples will be collected to measure plasma concentrations of NDI-034858.
Interventions
DRUGNDI-034858
NDI-034858 oral capsule
OTHERPlacebo
NDI-034858-matching oral placebo capsule
Sponsors
Nimbus Lakshmi, Inc.
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Treatment and randomization information will be kept confidential and will not be released to the investigator, the study staff, the contract research organization (CRO), or the sponsor's study team until after the conclusion of the study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Participant has PsA on the basis of the Classification Criteria for Psoriatic Arthritis with peripheral symptoms at the screening visit. * Participant has a history of PsA symptoms for ≥ 6 months prior to the screening visit. * Participant has ≥ 3 tender joints and ≥ 3 swollen joints at screening and Day 1 visits. * Participant has at least one lesion of plaque psoriasis ≥ 2 cm in diameter, nail changes characteristic of psoriasis, or a documented history of plaque psoriasis. * Participant has active PsA despite previous standard doses of non-steroidal anti-inflammatory drug (NSAIDs) administered for ≥ 4 weeks, or traditional disease-modifying anti-rheumatic drug (DMARDs) (including methotrexate and sulfasalazine) administered for ≥ 3 months, or tumor necrosis factor inhibitor (TNFi) agents administered for ≥ 3 months, or participants are intolerant to NSAIDs or DMARDs or TNFi agents. * If participant is on concurrent PsA treatments, they must be on stable doses. * All female participants should followed the protocol defined contraceptive method.
Exclusion criteria
* Participant has other disease(s) that might confound the evaluations of benefit of NDI-034858 therapy, including but not limited to rheumatoid arthritis (RA), axial spondyloarthritis (this does not include a primary diagnosis of PsA with spondylitis), systemic lupus erythematosus, Lyme disease, or fibromyalgia. * Participant has a history of lack of response to any therapeutic agent targeting IL-12, IL17, and/or IL23 at approved doses after at least 12 weeks of therapy, and/or received one of these therapies within 6 months prior to baseline (Day 1). * Participant has a history of lack of response to \> 1 therapeutic agent targeting tumor necrosis factor. * Participant has received infliximab, golimumab, adalimumab, or certolizumab pegol, or any biosimilar of these agents, within 8 weeks prior to baseline (Day 1). * Participant has received etanercept, or any biosimilar of etanercept, within 4 weeks prior to baseline (Day 1). * Participant has received rituximab or any immune-cell-depleting therapy within 6 months prior to baseline (Day 1). * Participant has received any marketed or investigational biological agent, other than those specified in other inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved at Least an American College of Rheumatology 20 (ACR20) Response at Week 12 | Week 12 | ACR20 is composite measure defined as improvement of 20 percent(%) from baseline in both number of tender (68) & number of swollen (66) joints & a 20% improvement in at least 3 of following 5 criteria: patient global assessment of psoriatic arthritis (PGA-PsA) \[visual analog scale (VAS) where, 0=very good, no symptoms & 100=very poor, severe symptoms\], physician global assessment of psoriatic arthritis (PhGA-PsA) \[(VAS) where 0=no disease activity & 100=maximum disease activity\], patient global assessment of psoriatic arthritis pain (PGAAP) \[(VAS) where 0=no pain & 100=most severe pain\], disability history questionnaire i.e., Health Assessment Questionnaire-Disability Index \[HAQ-DI\] (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip & activities, 0=without difficulty to 3=unable to do) & acute phase reactant like high sensitivity C-reactive protein \[hsCRP\]). Percentages are rounded off to the nearest decimal. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved at Least an ACR-70 Response at Week 12 | Week 12 | The ACR-70 is a composite measure defined as improvement of 70% from baseline in both the number of tender (68) and number of swollen (66) joints, and a 70% improvement in at least three of the following five criteria: PGA-PsA (VAS where, 0 is 'very good, no symptoms' and 100 is 'very poor, severe symptoms'), PhGA-PsA \[(VAS) where 0=no disease activity and 100=maximum disease activity\], PGAAP \[(VAS) where 0=no pain & 100=most severe pain\], disability history questionnaire (i.e., HAQ-DI) \[20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do\] and an acute phase reactant (i.e., ESR or CRP). Percentages are rounded off to the nearest decimal. |
| Change From Baseline in Tender Joint Count (TJC) at Week 12 | Baseline, Week 12 | The TJC 68 is a total score of points assigned for the presence of tenderness in the 68 joints in the upper body and upper/lower extremity. The response to tenderness for each joint was evaluated using the following scale: 'Present' was assigned a score of 1 whereas, 'Absent', 'Not Done', 'Not Applicable', or joints with missing response were assigned a score of 0. The sum of all tender joints was derived. The overall tender joint count ranged from 0 to 68, with a higher score indicating a greater degree of tenderness. A negative change from baseline indicates improvement. |
| Change From Baseline in Swollen Joint Count (SJC) at Week 12 | Baseline, Week 12 | The SJC 66 (TJC 68 joint assessment minus hip joints, which cannot be assessed for swelling) is a total score of points assigned for presence of swelling in the 66 joints in the upper body and upper/lower extremity. The response to swelling for each joint was evaluated using the following scale: 'Present' was assigned a score of 1 whereas, 'Absent', 'Not Done', 'Not Applicable', or joints with missing response were assigned a score of 0. The sum of all swollen joints was derived. The overall swollen joint count ranged from 0 to 66, with a higher score indicating a greater degree of swelling. A negative change from baseline indicates improvement. |
| Change From Baseline in PGA-PsA at Week 12 | Baseline, Week 12 | Participants assessed their overall disease status based on symptoms of psoriasis and psoriatic arthritis at the time of the visit using the PGA-PsA VAS of 100 millimeters (mm) which ranges from 0 (very good, no symptoms) to 100 (very poor, severe symptoms). A negative change from Baseline indicates improvement in symptoms. |
| Change From Baseline in PGAAP at Week 12 | Baseline, Week 12 | Participants assessed their overall psoriatic arthritis-related pain at the time of the visit using the PGAAP VAS of 100 mm which ranges from 0 (no pain) to 100 (most severe pain). A negative change from Baseline indicates improvement in pain. |
| Change From Baseline in PhGA-PsA at Week 12 | Baseline, Week 12 | The participants' overall disease status was assessed, taking into account signs, symptoms, and function, of all components of joint and skin affected at the time of the visit and this overall status was rated by the investigator using the PhGA-PsA VAS of 100 mm where 0 is 'very good, asymptomatic, and no limitation of normal activities' and 100 is 'very poor, very severe symptoms which are intolerable, and inability to carry out all normal activities'. A negative change from Baseline indicates improvement in symptoms. |
| Change From Baseline in HAQ-DI Total Score at Week 12 | Baseline, Week 12 | The HAQ-DI consists of 20 questions referring to eight domains consisting of dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Each item is scored from 0 (without any difficulty) to 3 (unable to do). The worst score within each domain will be used as the domain score (i.e., if the score for one question is 1 and 2 for the other, then the worst score for the domain is 2). The HAQ-DI total score is calculated by dividing the sum of the domain scores by the number of non-missing domains. The total score indicates the patient's self-assessed level of functional ability and higher scores indicate worse functional ability. The HAQ-DI total score ranges from 0 to 3. A higher score indicates worse function and greater disability. A negative change from Baseline indicates improved function. |
| Percentage of Participants Who Achieved at Least an ACR-50 Response at Week 12 | Week 12 | The ACR-50 is a composite measure defined as improvement of 50% from baseline in both the number of tender (68) and number of swollen (66) joints, and a 50% improvement in at least three of the following five criteria: PGA-PsA (VAS where, 0 is 'very good, no symptoms' and 100 is 'very poor, severe symptoms'), PhGA-PsA \[(VAS) where 0=no disease activity and 100=maximum disease activity\], PGAAP \[(VAS) where 0=no pain & 100=most severe pain\], disability history questionnaire (i.e., HAQ-DI) \[20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do\] and an acute phase reactant \[i.e., erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP)\]. Percentages are rounded off to the nearest decimal. |
| Change From Baseline in Leeds Enthesitis Index (LEI) at Week 12 | Baseline, Week 12 | Enthesitis is assessed using LEI. The enthesitis examination by LEI evaluates the presence or absence of pain by applying local pressure on 6 anatomical sites: medial femoral condyle (left and right), lateral epicondyle (left and right), and the achilles tendon insertion (left and right). Enthesitis at each site is scored as 0 (enthesitis absent) and 1 (enthesitis present). LEI is derived as the sum of the enthesitis score over the 6 sites, divided by the number of sites with non-missing score. The total score ranges from 0 to 6, higher scores indicate greater degree of enthesitis. A negative change from baseline indicates improvement. |
| Percentage of Participants With Minimal Disease Activity (MDA) Response at Week 12 | Week 12 | MDA is a measure to indicate a state of minimal disease activity, and is a composite score of 7 domains. A participant is considered as having achieved the MDA if the participant fulfills at least 5 of the following 7 criteria: TJC 68 ≤1; SJC 66 ≤1; Psoriasis area and severity index (PASI) score ≤1 \[The total score ranges from 0 (no disease) to 72 (maximal disease)\] or body surface area (BSA) ≤3%; PGAAP ≤15 \[using VAS on a scale of 0 (no pain) to 100 (serious pain)\]; PGA-PsA ≤20 \[using VAS on a scale of 0 (very well) to 100 (very poor)\]; HAQ-DI score ≤0.5; LEI score ≤1. Percentages are rounded off to the nearest decimal. |
| Change From Baseline in Disease Activity Index for Psoriatic Arthritis (DAPSA) at Week 12 | Baseline, Week 12 | The DAPSA score is a composite score and was calculated using: TJC68, SJC66, PGA-PsA, PGAAP, and hsCRP level (milligram per deciliter \[mg/dL\]). DAPSA scores 0-4 = remission, 5-14 = low disease activity, 15-28 = moderate disease activity, and \>28 = high disease activity. The DAPSA score has a lower bound of 0 and has no upper bound. A higher DAPSA score indicated more active disease activity. A negative change from baseline indicates improvement. |
| Percentage of Participants Who Achieved PASI-75 Response at Week 12 | Week 12 | PASI-75 is assessed in participants with psoriasis involvement for ≥ 3% of the BSA at Baseline and assesses the extent of involvement and severity of psoriasis. To calculate the PASI, the body is divided into 4 regions: the head and neck, trunk, upper limbs, and lower limbs. Each of these areas are assessed separately for the percentage of the area involved and for erythema, induration, and scaling, which are each rated on a scale of 0 to 4, which translates to a numeric score that ranges from 0 (indicates no involvement) to 6 (90% to 100% involvement). The PASI produces a numeric score that can range from 0 (no disease) to 72 (maximal disease). For PASI-75, the improvement threshold from baseline in PASI score is 75%. A higher score indicates more severe disease. Percentages are rounded off to the nearest decimal. |
| Percentage of Participants Who Achieved a Physician Global Assessment of Psoriasis (PhGA-PsO) of 0 or 1 and at Least a 2-point Improvement at Week 12 | Week 12 | PhGA-PsO responder is defined as participants 1) who had PhGA-PsO score of 0 or 1 at any given post-baseline visit; and 2) who had at least 2-point improvement from baseline. The PhGA-PsO is measured using a 0 to 4 scale with a 0 meaning clear or a 4 meaning severe. The proportion of participants achieving PhGA-PsO response at Week 12 was calculated and analyzed for participants with a score of at least 2 at baseline. Percentages are rounded off to the nearest decimal. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | From first dose of study drug up to end of study (up to Week 16) | Adverse Event(AE)=medical occurrence that does not necessarily have a causal relationship with this drug also including clinically meaningful findings in laboratory safety tests,vital signs,weight,and electrocardiogram(ECG).TEAEs=AEs occurring at time of or post study drug dosing until study end.SAE=any medical occurrence at any dose that resulted in death,was life-threatening,required inpatient hospitalization/prolongation of existing hospitalization,resulted in persistent or significant disability/incapacity,was a congenital abnormality/birth defect,an important medical event.AESIs included Common Terminology Criteria for Adverse Events(CTCAE)Grade≥2 cytopenia,CTCAE Grade≥3 elevation of creatine phosphokinase(CPK)\[clinically significant or not\]defined as CPK\>5xupper limit of normal(ULN),infections,adverse events of abnormal liver function tests,adverse events of renal dysfunction,major adverse cardiovascular events,thromboembolic events,gastrointestinal perforation,and malignancies. |
| Plasma Concentration of NDI-034858 | Pre-dose, 1 hour post-dose on Day 1 and Week 4, 4 hours post-dose at Week 4, Pre-dose at Week 8, and anytime at Week 12 | Plasma concentration of NDI-034858 was measured in participants who received low, medium, or high doses of NDI-034858. |
| Change From Baseline in Dactylitis Count (DC) at Week 12 | Baseline, Week 12 | Tender score (0 = no tenderness, 1 = tender, 2 = tender and wince, 3 = tender and withdraw) is collected for Dactylitis Assessments on the Dactylitis Score Sheet that is used for calculation of total score. DC equals the number of tender fingers and toes (tender score \>0). For participants with dactylitis status absent for all the fingers and toes, the DC is set as 0. The total score range of DC is from 0 to 60, higher scores indicate greater presence of dactylitis. A negative change from baseline indicates improvement. |
Countries
Czechia, Germany, Poland, United States
Participant flow
Recruitment details
Participants took part in the study at 45 investigative sites in the United States (US), Germany, Poland, and the Czech Republic from 6 January 2022 to 2 June 2023.
Pre-assignment details
A total of 305 participants with a diagnosis of psoriatic arthritis were enrolled in a 1:1:1:1 ratio to receive either one of the 3 doses of NDI-034858 or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo capsules, orally, QD for 12 weeks. | 72 |
| NDI-034858 Low Dose Participants received NDI-034858 low dose, capsules, orally, QD for 12 weeks. | 71 |
| NDI-034858 Medium Dose Participants received NDI-034858 medium dose, capsules, orally, QD for 12 weeks. | 75 |
| NDI-034858 High Dose Participants received NDI-034858 high dose, capsules, orally, QD for 12 weeks. | 72 |
| Total | 290 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 3 | 5 |
| Overall Study | Coronavirus Disease 2019 (COVID-19) | 0 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 | 2 | 0 |
| Overall Study | Randomized Without Dosing due to Ineligibility | 0 | 0 | 0 | 2 |
| Overall Study | Reason not Specified | 1 | 1 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 6 | 8 | 6 | 8 |
Baseline characteristics
| Characteristic | NDI-034858 Low Dose | NDI-034858 Medium Dose | Placebo | NDI-034858 High Dose | Total |
|---|---|---|---|---|---|
| Age, Continuous | 48.3 years STANDARD_DEVIATION 10.43 | 52.5 years STANDARD_DEVIATION 12.15 | 49.7 years STANDARD_DEVIATION 11.83 | 49.0 years STANDARD_DEVIATION 11.51 | 49.9 years STANDARD_DEVIATION 11.56 |
| Body Mass Index (BMI) | 29.78 kilograms per meter square (kg/m^2) STANDARD_DEVIATION 8.153 | 30.04 kilograms per meter square (kg/m^2) STANDARD_DEVIATION 7.937 | 29.48 kilograms per meter square (kg/m^2) STANDARD_DEVIATION 6.865 | 30.15 kilograms per meter square (kg/m^2) STANDARD_DEVIATION 6.61 | 29.87 kilograms per meter square (kg/m^2) STANDARD_DEVIATION 7.39 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 4 Participants | 2 Participants | 2 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 69 Participants | 71 Participants | 70 Participants | 70 Participants | 280 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Height | 170.1 centimeters (cm) STANDARD_DEVIATION 8.67 | 169.0 centimeters (cm) STANDARD_DEVIATION 9.04 | 170.3 centimeters (cm) STANDARD_DEVIATION 10.65 | 170.4 centimeters (cm) STANDARD_DEVIATION 9.06 | 169.9 centimeters (cm) STANDARD_DEVIATION 9.35 |
| Race/Ethnicity, Customized Missing | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Non-white | 3 Participants | 4 Participants | 1 Participants | 3 Participants | 11 Participants |
| Race/Ethnicity, Customized White | 66 Participants | 71 Participants | 69 Participants | 69 Participants | 275 Participants |
| Sex: Female, Male Female | 40 Participants | 46 Participants | 37 Participants | 43 Participants | 166 Participants |
| Sex: Female, Male Male | 31 Participants | 29 Participants | 35 Participants | 29 Participants | 124 Participants |
| Weight | 86.97 kilograms (kg) STANDARD_DEVIATION 26.611 | 85.85 kilograms (kg) STANDARD_DEVIATION 22.048 | 86.26 kilograms (kg) STANDARD_DEVIATION 25.307 | 87.74 kilograms (kg) STANDARD_DEVIATION 20.152 | 86.69 kilograms (kg) STANDARD_DEVIATION 23.529 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 75 | 0 / 76 | 0 / 78 | 0 / 76 |
| other Total, other adverse events | 13 / 72 | 19 / 71 | 27 / 75 | 35 / 72 |
| serious Total, serious adverse events | 4 / 72 | 4 / 71 | 3 / 75 | 2 / 72 |
Outcome results
Primary
Percentage of Participants Who Achieved at Least an American College of Rheumatology 20 (ACR20) Response at Week 12
ACR20 is composite measure defined as improvement of 20 percent(%) from baseline in both number of tender (68) & number of swollen (66) joints & a 20% improvement in at least 3 of following 5 criteria: patient global assessment of psoriatic arthritis (PGA-PsA) \[visual analog scale (VAS) where, 0=very good, no symptoms & 100=very poor, severe symptoms\], physician global assessment of psoriatic arthritis (PhGA-PsA) \[(VAS) where 0=no disease activity & 100=maximum disease activity\], patient global assessment of psoriatic arthritis pain (PGAAP) \[(VAS) where 0=no pain & 100=most severe pain\], disability history questionnaire i.e., Health Assessment Questionnaire-Disability Index \[HAQ-DI\] (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip & activities, 0=without difficulty to 3=unable to do) & acute phase reactant like high sensitivity C-reactive protein \[hsCRP\]). Percentages are rounded off to the nearest decimal.
Time frame: Week 12
Population: Full Analysis Set included all randomized participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved at Least an American College of Rheumatology 20 (ACR20) Response at Week 12 | 29.2 percentage of participants |
| NDI-034858 Low Dose | Percentage of Participants Who Achieved at Least an American College of Rheumatology 20 (ACR20) Response at Week 12 | 35.2 percentage of participants |
| NDI-034858 Medium Dose | Percentage of Participants Who Achieved at Least an American College of Rheumatology 20 (ACR20) Response at Week 12 | 53.3 percentage of participants |
| NDI-034858 High Dose | Percentage of Participants Who Achieved at Least an American College of Rheumatology 20 (ACR20) Response at Week 12 | 54.2 percentage of participants |
p-value: =0.44695% CI: [-9.3, 21.1]Cochran-Mantel-Haenszel
p-value: =0.00295% CI: [8.6, 39.6]Cochran-Mantel-Haenszel
p-value: =0.00295% CI: [9, 39.9]Cochran-Mantel-Haenszel
Secondary
Change From Baseline in Dactylitis Count (DC) at Week 12
Tender score (0 = no tenderness, 1 = tender, 2 = tender and wince, 3 = tender and withdraw) is collected for Dactylitis Assessments on the Dactylitis Score Sheet that is used for calculation of total score. DC equals the number of tender fingers and toes (tender score \>0). For participants with dactylitis status absent for all the fingers and toes, the DC is set as 0. The total score range of DC is from 0 to 60, higher scores indicate greater presence of dactylitis. A negative change from baseline indicates improvement.
Time frame: Baseline, Week 12
Population: Full Analysis Set included all randomized participants who received at least one dose of study drug. Overall number analyzed is the number of participants with dactylitis at Baseline and with available data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Dactylitis Count (DC) at Week 12 | -2.1 dactylitis count | Standard Error 0.39 |
| NDI-034858 Low Dose | Change From Baseline in Dactylitis Count (DC) at Week 12 | -0.8 dactylitis count | Standard Error 0.41 |
| NDI-034858 Medium Dose | Change From Baseline in Dactylitis Count (DC) at Week 12 | -2.0 dactylitis count | Standard Error 0.47 |
| NDI-034858 High Dose | Change From Baseline in Dactylitis Count (DC) at Week 12 | -1.9 dactylitis count | Standard Error 0.41 |
p-value: =0.03195% CI: [0.1, 2.4]MMRM
p-value: =0.8695% CI: [-1.1, 1.3]MMRM
p-value: =0.75895% CI: [-0.9, 1.3]MMRM
Secondary
Change From Baseline in Disease Activity Index for Psoriatic Arthritis (DAPSA) at Week 12
The DAPSA score is a composite score and was calculated using: TJC68, SJC66, PGA-PsA, PGAAP, and hsCRP level (milligram per deciliter \[mg/dL\]). DAPSA scores 0-4 = remission, 5-14 = low disease activity, 15-28 = moderate disease activity, and \>28 = high disease activity. The DAPSA score has a lower bound of 0 and has no upper bound. A higher DAPSA score indicated more active disease activity. A negative change from baseline indicates improvement.
Time frame: Baseline, Week 12
Population: Full Analysis Set included all randomized participants who received at least one dose of study drug. Overall number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Disease Activity Index for Psoriatic Arthritis (DAPSA) at Week 12 | -11.56 score on a scale | Standard Error 1.948 |
| NDI-034858 Low Dose | Change From Baseline in Disease Activity Index for Psoriatic Arthritis (DAPSA) at Week 12 | -15.30 score on a scale | Standard Error 1.946 |
| NDI-034858 Medium Dose | Change From Baseline in Disease Activity Index for Psoriatic Arthritis (DAPSA) at Week 12 | -17.99 score on a scale | Standard Error 1.943 |
| NDI-034858 High Dose | Change From Baseline in Disease Activity Index for Psoriatic Arthritis (DAPSA) at Week 12 | -16.79 score on a scale | Standard Error 1.989 |
p-value: =0.16795% CI: [-9.04, 1.57]MMRM
p-value: =0.01895% CI: [-11.73, -1.13]MMRM
p-value: =0.05695% CI: [-10.59, 0.13]MMRM
Secondary
Change From Baseline in HAQ-DI Total Score at Week 12
The HAQ-DI consists of 20 questions referring to eight domains consisting of dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Each item is scored from 0 (without any difficulty) to 3 (unable to do). The worst score within each domain will be used as the domain score (i.e., if the score for one question is 1 and 2 for the other, then the worst score for the domain is 2). The HAQ-DI total score is calculated by dividing the sum of the domain scores by the number of non-missing domains. The total score indicates the patient's self-assessed level of functional ability and higher scores indicate worse functional ability. The HAQ-DI total score ranges from 0 to 3. A higher score indicates worse function and greater disability. A negative change from Baseline indicates improved function.
Time frame: Baseline, Week 12
Population: Full Analysis Set included all randomized participants who received at least one dose of study drug. Overall number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in HAQ-DI Total Score at Week 12 | -0.22 score on a scale | Standard Error 0.053 |
| NDI-034858 Low Dose | Change From Baseline in HAQ-DI Total Score at Week 12 | -0.29 score on a scale | Standard Error 0.053 |
| NDI-034858 Medium Dose | Change From Baseline in HAQ-DI Total Score at Week 12 | -0.32 score on a scale | Standard Error 0.053 |
| NDI-034858 High Dose | Change From Baseline in HAQ-DI Total Score at Week 12 | -0.28 score on a scale | Standard Error 0.055 |
p-value: =0.35795% CI: [-0.21, 0.08]MMRM
p-value: =0.19595% CI: [-0.24, 0.05]MMRM
p-value: =0.46795% CI: [-0.2, 0.09]MMRM
Secondary
Change From Baseline in Leeds Enthesitis Index (LEI) at Week 12
Enthesitis is assessed using LEI. The enthesitis examination by LEI evaluates the presence or absence of pain by applying local pressure on 6 anatomical sites: medial femoral condyle (left and right), lateral epicondyle (left and right), and the achilles tendon insertion (left and right). Enthesitis at each site is scored as 0 (enthesitis absent) and 1 (enthesitis present). LEI is derived as the sum of the enthesitis score over the 6 sites, divided by the number of sites with non-missing score. The total score ranges from 0 to 6, higher scores indicate greater degree of enthesitis. A negative change from baseline indicates improvement.
Time frame: Baseline, Week 12
Population: Full Analysis Set included all randomized participants who received at least one dose of study drug. Overall number analyzed is the number of participants who had a baseline LEI score of ≥1 and with data available for analyses.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Leeds Enthesitis Index (LEI) at Week 12 | -0.9 score on a scale | Standard Error 0.24 |
| NDI-034858 Low Dose | Change From Baseline in Leeds Enthesitis Index (LEI) at Week 12 | -1.4 score on a scale | Standard Error 0.24 |
| NDI-034858 Medium Dose | Change From Baseline in Leeds Enthesitis Index (LEI) at Week 12 | -1.6 score on a scale | Standard Error 0.24 |
| NDI-034858 High Dose | Change From Baseline in Leeds Enthesitis Index (LEI) at Week 12 | -1.0 score on a scale | Standard Error 0.25 |
p-value: =0.13195% CI: [-1.2, 0.2]MMRM
p-value: =0.04395% CI: [-1.3, 0]MMRM
p-value: =0.68795% CI: [-0.8, 0.5]MMRM
Secondary
Change From Baseline in PGAAP at Week 12
Participants assessed their overall psoriatic arthritis-related pain at the time of the visit using the PGAAP VAS of 100 mm which ranges from 0 (no pain) to 100 (most severe pain). A negative change from Baseline indicates improvement in pain.
Time frame: Baseline, Week 12
Population: Full Analysis Set included all randomized participants who received at least one dose of study drug. Overall number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in PGAAP at Week 12 | -12.1 mm | Standard Error 2.75 |
| NDI-034858 Low Dose | Change From Baseline in PGAAP at Week 12 | -13.0 mm | Standard Error 2.74 |
| NDI-034858 Medium Dose | Change From Baseline in PGAAP at Week 12 | -18.8 mm | Standard Error 2.75 |
| NDI-034858 High Dose | Change From Baseline in PGAAP at Week 12 | -18.4 mm | Standard Error 2.82 |
p-value: =0.81295% CI: [-8.4, 6.6]MMRM
p-value: =0.07995% CI: [-14.2, 0.8]MMRM
p-value: =0.10295% CI: [-13.9, 1.3]MMRM
Secondary
Change From Baseline in PGA-PsA at Week 12
Participants assessed their overall disease status based on symptoms of psoriasis and psoriatic arthritis at the time of the visit using the PGA-PsA VAS of 100 millimeters (mm) which ranges from 0 (very good, no symptoms) to 100 (very poor, severe symptoms). A negative change from Baseline indicates improvement in symptoms.
Time frame: Baseline, Week 12
Population: Full Analysis Set included all randomized participants who received at least one dose of study drug. Overall number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in PGA-PsA at Week 12 | -11.1 mm | Standard Error 2.85 |
| NDI-034858 Low Dose | Change From Baseline in PGA-PsA at Week 12 | -12.9 mm | Standard Error 2.84 |
| NDI-034858 Medium Dose | Change From Baseline in PGA-PsA at Week 12 | -20.2 mm | Standard Error 2.85 |
| NDI-034858 High Dose | Change From Baseline in PGA-PsA at Week 12 | -19.8 mm | Standard Error 2.92 |
p-value: =0.63795% CI: [-9.6, 5.9]MMRM
p-value: =0.02195% CI: [-17, -1.4]MMRM
p-value: =0.0395% CI: [-16.5, -0.9]MMRM
Secondary
Change From Baseline in PhGA-PsA at Week 12
The participants' overall disease status was assessed, taking into account signs, symptoms, and function, of all components of joint and skin affected at the time of the visit and this overall status was rated by the investigator using the PhGA-PsA VAS of 100 mm where 0 is 'very good, asymptomatic, and no limitation of normal activities' and 100 is 'very poor, very severe symptoms which are intolerable, and inability to carry out all normal activities'. A negative change from Baseline indicates improvement in symptoms.
Time frame: Baseline, Week 12
Population: Full Analysis Set included all randomized participants who received at least one dose of study drug. Overall number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in PhGA-PsA at Week 12 | -20.7 mm | Standard Error 2.66 |
| NDI-034858 Low Dose | Change From Baseline in PhGA-PsA at Week 12 | -29.6 mm | Standard Error 2.65 |
| NDI-034858 Medium Dose | Change From Baseline in PhGA-PsA at Week 12 | -31.3 mm | Standard Error 2.65 |
| NDI-034858 High Dose | Change From Baseline in PhGA-PsA at Week 12 | -31.6 mm | Standard Error 2.73 |
p-value: =0.01695% CI: [-16.2, -1.7]MMRM
p-value: =0.00495% CI: [-17.8, -3.4]MMRM
p-value: =0.00395% CI: [-18.2, -3.6]MMRM
Secondary
Change From Baseline in Swollen Joint Count (SJC) at Week 12
The SJC 66 (TJC 68 joint assessment minus hip joints, which cannot be assessed for swelling) is a total score of points assigned for presence of swelling in the 66 joints in the upper body and upper/lower extremity. The response to swelling for each joint was evaluated using the following scale: 'Present' was assigned a score of 1 whereas, 'Absent', 'Not Done', 'Not Applicable', or joints with missing response were assigned a score of 0. The sum of all swollen joints was derived. The overall swollen joint count ranged from 0 to 66, with a higher score indicating a greater degree of swelling. A negative change from baseline indicates improvement.
Time frame: Baseline, Week 12
Population: Full Analysis Set included all randomized participants who received at least one dose of study drug. Overall number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Swollen Joint Count (SJC) at Week 12 | -3.9 swollen joints | Standard Error 0.57 |
| NDI-034858 Low Dose | Change From Baseline in Swollen Joint Count (SJC) at Week 12 | -4.8 swollen joints | Standard Error 0.58 |
| NDI-034858 Medium Dose | Change From Baseline in Swollen Joint Count (SJC) at Week 12 | -5.0 swollen joints | Standard Error 0.58 |
| NDI-034858 High Dose | Change From Baseline in Swollen Joint Count (SJC) at Week 12 | -5.0 swollen joints | Standard Error 0.59 |
p-value: =0.2895% CI: [-2.4, 0.7]MMRM
p-value: =0.17795% CI: [-2.6, 0.5]MMRM
p-value: =0.19695% CI: [-2.6, 0.5]MMRM
Secondary
Change From Baseline in Tender Joint Count (TJC) at Week 12
The TJC 68 is a total score of points assigned for the presence of tenderness in the 68 joints in the upper body and upper/lower extremity. The response to tenderness for each joint was evaluated using the following scale: 'Present' was assigned a score of 1 whereas, 'Absent', 'Not Done', 'Not Applicable', or joints with missing response were assigned a score of 0. The sum of all tender joints was derived. The overall tender joint count ranged from 0 to 68, with a higher score indicating a greater degree of tenderness. A negative change from baseline indicates improvement.
Time frame: Baseline, Week 12
Population: Full Analysis Set included all randomized participants who received at least one dose of study drug. Overall number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Tender Joint Count (TJC) at Week 12 | -5.9 tender joints | Standard Error 1.12 |
| NDI-034858 Low Dose | Change From Baseline in Tender Joint Count (TJC) at Week 12 | -7.6 tender joints | Standard Error 1.12 |
| NDI-034858 Medium Dose | Change From Baseline in Tender Joint Count (TJC) at Week 12 | -8.9 tender joints | Standard Error 1.12 |
| NDI-034858 High Dose | Change From Baseline in Tender Joint Count (TJC) at Week 12 | -8.3 tender joints | Standard Error 1.15 |
p-value: =0.26895% CI: [-4.8, 1.3]Mixed Model Repeated Measure (MMRM)
p-value: =0.05195% CI: [-6.1, 0]MMRM
p-value: =0.11295% CI: [-5.6, 0.6]MMRM
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)
Adverse Event(AE)=medical occurrence that does not necessarily have a causal relationship with this drug also including clinically meaningful findings in laboratory safety tests,vital signs,weight,and electrocardiogram(ECG).TEAEs=AEs occurring at time of or post study drug dosing until study end.SAE=any medical occurrence at any dose that resulted in death,was life-threatening,required inpatient hospitalization/prolongation of existing hospitalization,resulted in persistent or significant disability/incapacity,was a congenital abnormality/birth defect,an important medical event.AESIs included Common Terminology Criteria for Adverse Events(CTCAE)Grade≥2 cytopenia,CTCAE Grade≥3 elevation of creatine phosphokinase(CPK)\[clinically significant or not\]defined as CPK\>5xupper limit of normal(ULN),infections,adverse events of abnormal liver function tests,adverse events of renal dysfunction,major adverse cardiovascular events,thromboembolic events,gastrointestinal perforation,and malignancies.
Time frame: From first dose of study drug up to end of study (up to Week 16)
Population: Safety Analysis Set included all randomized participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | TEAEs | 39 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | AESIs | 19 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | SAEs | 4 Participants |
| NDI-034858 Low Dose | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | TEAEs | 42 Participants |
| NDI-034858 Low Dose | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | AESIs | 33 Participants |
| NDI-034858 Low Dose | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | SAEs | 4 Participants |
| NDI-034858 Medium Dose | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | SAEs | 3 Participants |
| NDI-034858 Medium Dose | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | TEAEs | 45 Participants |
| NDI-034858 Medium Dose | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | AESIs | 22 Participants |
| NDI-034858 High Dose | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | TEAEs | 56 Participants |
| NDI-034858 High Dose | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | AESIs | 38 Participants |
| NDI-034858 High Dose | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | SAEs | 2 Participants |
Secondary
Percentage of Participants Who Achieved a Physician Global Assessment of Psoriasis (PhGA-PsO) of 0 or 1 and at Least a 2-point Improvement at Week 12
PhGA-PsO responder is defined as participants 1) who had PhGA-PsO score of 0 or 1 at any given post-baseline visit; and 2) who had at least 2-point improvement from baseline. The PhGA-PsO is measured using a 0 to 4 scale with a 0 meaning clear or a 4 meaning severe. The proportion of participants achieving PhGA-PsO response at Week 12 was calculated and analyzed for participants with a score of at least 2 at baseline. Percentages are rounded off to the nearest decimal.
Time frame: Week 12
Population: Full Analysis Set included all randomized participants who received at least one dose of study drug. Overall number analyzed is the number of participants with PhGA-PSO ≥2 at Baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved a Physician Global Assessment of Psoriasis (PhGA-PsO) of 0 or 1 and at Least a 2-point Improvement at Week 12 | 15.8 percentage of participants |
| NDI-034858 Low Dose | Percentage of Participants Who Achieved a Physician Global Assessment of Psoriasis (PhGA-PsO) of 0 or 1 and at Least a 2-point Improvement at Week 12 | 20.4 percentage of participants |
| NDI-034858 Medium Dose | Percentage of Participants Who Achieved a Physician Global Assessment of Psoriasis (PhGA-PsO) of 0 or 1 and at Least a 2-point Improvement at Week 12 | 20.6 percentage of participants |
| NDI-034858 High Dose | Percentage of Participants Who Achieved a Physician Global Assessment of Psoriasis (PhGA-PsO) of 0 or 1 and at Least a 2-point Improvement at Week 12 | 32.8 percentage of participants |
p-value: =0.5495% CI: [-10, 19]Cochran-Mantel-Haenszel
p-value: =0.46695% CI: [-8.8, 19.3]Cochran-Mantel-Haenszel
p-value: =0.03495% CI: [1.2, 31.3]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieved at Least an ACR-50 Response at Week 12
The ACR-50 is a composite measure defined as improvement of 50% from baseline in both the number of tender (68) and number of swollen (66) joints, and a 50% improvement in at least three of the following five criteria: PGA-PsA (VAS where, 0 is 'very good, no symptoms' and 100 is 'very poor, severe symptoms'), PhGA-PsA \[(VAS) where 0=no disease activity and 100=maximum disease activity\], PGAAP \[(VAS) where 0=no pain & 100=most severe pain\], disability history questionnaire (i.e., HAQ-DI) \[20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do\] and an acute phase reactant \[i.e., erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP)\]. Percentages are rounded off to the nearest decimal.
Time frame: Week 12
Population: Full Analysis Set included all randomized participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved at Least an ACR-50 Response at Week 12 | 9.7 percentage of participants |
| NDI-034858 Low Dose | Percentage of Participants Who Achieved at Least an ACR-50 Response at Week 12 | 15.5 percentage of participants |
| NDI-034858 Medium Dose | Percentage of Participants Who Achieved at Least an ACR-50 Response at Week 12 | 26.7 percentage of participants |
| NDI-034858 High Dose | Percentage of Participants Who Achieved at Least an ACR-50 Response at Week 12 | 26.4 percentage of participants |
p-value: =0.31295% CI: [-5.3, 16.6]Cochran-Mantel-Haenszel
p-value: =0.00595% CI: [5, 29.1]Cochran-Mantel-Haenszel
p-value: =0.00995% CI: [4.2, 28.6]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieved at Least an ACR-70 Response at Week 12
The ACR-70 is a composite measure defined as improvement of 70% from baseline in both the number of tender (68) and number of swollen (66) joints, and a 70% improvement in at least three of the following five criteria: PGA-PsA (VAS where, 0 is 'very good, no symptoms' and 100 is 'very poor, severe symptoms'), PhGA-PsA \[(VAS) where 0=no disease activity and 100=maximum disease activity\], PGAAP \[(VAS) where 0=no pain & 100=most severe pain\], disability history questionnaire (i.e., HAQ-DI) \[20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do\] and an acute phase reactant (i.e., ESR or CRP). Percentages are rounded off to the nearest decimal.
Time frame: Week 12
Population: Full Analysis Set included all randomized participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved at Least an ACR-70 Response at Week 12 | 5.6 percentage of participants |
| NDI-034858 Low Dose | Percentage of Participants Who Achieved at Least an ACR-70 Response at Week 12 | 8.5 percentage of participants |
| NDI-034858 Medium Dose | Percentage of Participants Who Achieved at Least an ACR-70 Response at Week 12 | 14.7 percentage of participants |
| NDI-034858 High Dose | Percentage of Participants Who Achieved at Least an ACR-70 Response at Week 12 | 13.9 percentage of participants |
p-value: =0.10195% CI: [-1, 20.1]Fisher Exact
p-value: =0.53295% CI: [-6.6, 12.7]Fisher Exact
p-value: =0.15895% CI: [-1.7, 19.4]Fisher Exact
Secondary
Percentage of Participants Who Achieved PASI-75 Response at Week 12
PASI-75 is assessed in participants with psoriasis involvement for ≥ 3% of the BSA at Baseline and assesses the extent of involvement and severity of psoriasis. To calculate the PASI, the body is divided into 4 regions: the head and neck, trunk, upper limbs, and lower limbs. Each of these areas are assessed separately for the percentage of the area involved and for erythema, induration, and scaling, which are each rated on a scale of 0 to 4, which translates to a numeric score that ranges from 0 (indicates no involvement) to 6 (90% to 100% involvement). The PASI produces a numeric score that can range from 0 (no disease) to 72 (maximal disease). For PASI-75, the improvement threshold from baseline in PASI score is 75%. A higher score indicates more severe disease. Percentages are rounded off to the nearest decimal.
Time frame: Week 12
Population: Full Analysis Set included all randomized participants who received at least one dose of study drug. Overall number analyzed is the number of participants with psoriasis covering ≥ 3% of the BSA at Baseline and with available data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved PASI-75 Response at Week 12 | 15.4 percentage of participants |
| NDI-034858 Low Dose | Percentage of Participants Who Achieved PASI-75 Response at Week 12 | 25.6 percentage of participants |
| NDI-034858 Medium Dose | Percentage of Participants Who Achieved PASI-75 Response at Week 12 | 28.3 percentage of participants |
| NDI-034858 High Dose | Percentage of Participants Who Achieved PASI-75 Response at Week 12 | 45.7 percentage of participants |
p-value: =0.18695% CI: [-5.7, 29.4]Cochran-Mantel-Haenszel
p-value: =0.10195% CI: [-2.8, 32.1]Cochran-Mantel-Haenszel
p-value: =0.00295% CI: [10.5, 47.6]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Minimal Disease Activity (MDA) Response at Week 12
MDA is a measure to indicate a state of minimal disease activity, and is a composite score of 7 domains. A participant is considered as having achieved the MDA if the participant fulfills at least 5 of the following 7 criteria: TJC 68 ≤1; SJC 66 ≤1; Psoriasis area and severity index (PASI) score ≤1 \[The total score ranges from 0 (no disease) to 72 (maximal disease)\] or body surface area (BSA) ≤3%; PGAAP ≤15 \[using VAS on a scale of 0 (no pain) to 100 (serious pain)\]; PGA-PsA ≤20 \[using VAS on a scale of 0 (very well) to 100 (very poor)\]; HAQ-DI score ≤0.5; LEI score ≤1. Percentages are rounded off to the nearest decimal.
Time frame: Week 12
Population: Full Analysis Set included all randomized participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Minimal Disease Activity (MDA) Response at Week 12 | 12.5 percentage of participants |
| NDI-034858 Low Dose | Percentage of Participants With Minimal Disease Activity (MDA) Response at Week 12 | 18.3 percentage of participants |
| NDI-034858 Medium Dose | Percentage of Participants With Minimal Disease Activity (MDA) Response at Week 12 | 28.0 percentage of participants |
| NDI-034858 High Dose | Percentage of Participants With Minimal Disease Activity (MDA) Response at Week 12 | 29.2 percentage of participants |
p-value: =0.34995% CI: [-6.1, 17.4]Cochran-Mantel-Haenszel
p-value: =0.01795% CI: [2.8, 28.3]Cochran-Mantel-Haenszel
p-value: =0.01495% CI: [3.3, 29.3]Cochran-Mantel-Haenszel
Secondary
Plasma Concentration of NDI-034858
Plasma concentration of NDI-034858 was measured in participants who received low, medium, or high doses of NDI-034858.
Time frame: Pre-dose, 1 hour post-dose on Day 1 and Week 4, 4 hours post-dose at Week 4, Pre-dose at Week 8, and anytime at Week 12
Population: Pharmacokinetic (PK) Analysis Set included all participants in the Safety Analysis Set with at least one evaluable post-dose PK assessment. Number analyzed is the number of participants with data available for analysis at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Concentration of NDI-034858 | Day 1: 1 Hour | 5.860 nanograms per milliliter (ng/mL) | Standard Deviation 7.251 |
| Placebo | Plasma Concentration of NDI-034858 | Week 4: 4 Hours | 46.68 nanograms per milliliter (ng/mL) | Standard Deviation 25.85 |
| Placebo | Plasma Concentration of NDI-034858 | Week 4: 1 Hour | 33.03 nanograms per milliliter (ng/mL) | Standard Deviation 24.05 |
| Placebo | Plasma Concentration of NDI-034858 | Day 1: Pre-dose | 0.000 nanograms per milliliter (ng/mL) | Standard Deviation 0 |
| Placebo | Plasma Concentration of NDI-034858 | Week 12: Any Time | 24.85 nanograms per milliliter (ng/mL) | Standard Deviation 20.58 |
| Placebo | Plasma Concentration of NDI-034858 | Week 8: Pre-dose | 26.99 nanograms per milliliter (ng/mL) | Standard Deviation 21 |
| Placebo | Plasma Concentration of NDI-034858 | Week 4: Pre-dose | 25.26 nanograms per milliliter (ng/mL) | Standard Deviation 17.95 |
| NDI-034858 Low Dose | Plasma Concentration of NDI-034858 | Week 4: 1 Hour | 112.8 nanograms per milliliter (ng/mL) | Standard Deviation 81.19 |
| NDI-034858 Low Dose | Plasma Concentration of NDI-034858 | Day 1: Pre-dose | 0.000 nanograms per milliliter (ng/mL) | Standard Deviation 0 |
| NDI-034858 Low Dose | Plasma Concentration of NDI-034858 | Day 1: 1 Hour | 25.43 nanograms per milliliter (ng/mL) | Standard Deviation 37.21 |
| NDI-034858 Low Dose | Plasma Concentration of NDI-034858 | Week 4: Pre-dose | 82.11 nanograms per milliliter (ng/mL) | Standard Deviation 74.46 |
| NDI-034858 Low Dose | Plasma Concentration of NDI-034858 | Week 4: 4 Hours | 149.5 nanograms per milliliter (ng/mL) | Standard Deviation 90.56 |
| NDI-034858 Low Dose | Plasma Concentration of NDI-034858 | Week 8: Pre-dose | 78.29 nanograms per milliliter (ng/mL) | Standard Deviation 69.37 |
| NDI-034858 Low Dose | Plasma Concentration of NDI-034858 | Week 12: Any Time | 66.17 nanograms per milliliter (ng/mL) | Standard Deviation 51.81 |
| NDI-034858 Medium Dose | Plasma Concentration of NDI-034858 | Week 4: 4 Hours | 370.1 nanograms per milliliter (ng/mL) | Standard Deviation 178.4 |
| NDI-034858 Medium Dose | Plasma Concentration of NDI-034858 | Day 1: 1 Hour | 38.32 nanograms per milliliter (ng/mL) | Standard Deviation 59.74 |
| NDI-034858 Medium Dose | Plasma Concentration of NDI-034858 | Week 12: Any Time | 178.2 nanograms per milliliter (ng/mL) | Standard Deviation 149.5 |
| NDI-034858 Medium Dose | Plasma Concentration of NDI-034858 | Week 8: Pre-dose | 209.4 nanograms per milliliter (ng/mL) | Standard Deviation 182 |
| NDI-034858 Medium Dose | Plasma Concentration of NDI-034858 | Week 4: 1 Hour | 245.3 nanograms per milliliter (ng/mL) | Standard Deviation 184.6 |
| NDI-034858 Medium Dose | Plasma Concentration of NDI-034858 | Week 4: Pre-dose | 187.5 nanograms per milliliter (ng/mL) | Standard Deviation 140.9 |
| NDI-034858 Medium Dose | Plasma Concentration of NDI-034858 | Day 1: Pre-dose | 0.000 nanograms per milliliter (ng/mL) | Standard Deviation 0 |