A Study to Evaluate the Efficacy, Safety, and Tolerability of NDI-034858 in Participants With Active Psoriatic Arthritis

Psoriatic Arthritis Clinical Trial

Official title:

A Phase 2b, Randomized, Multi-Center, Double-Blind, Placebo-Controlled, Multiple Dose Study to Evaluate the Efficacy, Safety, and Tolerability of NDI-034858 in Subjects With Active Psoriatic Arthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05153148
• Other study ID #: 4858-202
• Secondary ID: 2021-005888-52
• Status: Completed
• Phase: Phase 2
• Start date: January 6, 2022
• Est. completion date: June 2, 2023

Study information

• Verified date: May 2024
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is designed to evaluate the efficacy, safety, and tolerability of NDI-034858 in participants with active Psoriatic Arthritis (PsA).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 305
• Est. completion date: June 2, 2023
• Est. primary completion date: May 4, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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/exclusion criteria, within 12 weeks or 5 half-lives prior to baseline (Day 1).

• Participant is currently receiving a non-biological investigational product or device or has received one within 4 weeks prior to baseline (Day 1).

• Participant has received apremilast or other non-biologic systemic treatment for PsA within 4 weeks prior to baseline (Day 1), other than methotrexate (MTX), sulfasalazine, corticosteroids, NSAIDs, or paracetamol/acetaminophen, which are allowed at stable doses as described in Inclusion Criterion 7. For participants not receiving MTX and sulfasalazine at screening, MTX and sulfasalazine are excluded within 4 weeks prior to baseline (Day 1). Participant has received leflunomide within 8 weeks of baseline (Day 1) if no elimination procedure was followed or adhere to an elimination procedure. For participants not receiving MTX and sulfasalazine at Screening, MTX and sulfasalazine are excluded within 4 weeks prior to baseline (Day 1).

• Participant has received intraarticular injection (including corticosteroids), intramuscular steroids, intralesional steroids, or intravenous steroids within 4 weeks prior to baseline (Day 1). For participants not receiving MTX and sulfasalazine at screening, MTX and sulfasalazine are excluded within 4 weeks prior to baseline (Day 1). For participants not receiving MTX and sulfasalazine at screening, MTX and sulfasalazine are excluded within 4 weeks prior to baseline (Day 1).

• Participant has received high potency opioid analgesics (eg, methadone, hydromorphone, or morphine) within 2 weeks prior to baseline (Day 1).

• Participant has used any topical medication that could affect PsA or psoriasis (including corticosteroids, retinoids, vitamin D analogues (such as calcipotriol), JAK inhibitors, or tar) within 2 weeks prior to baseline (Day 1).

• Participant has used any systemic treatment that could affect PsA or psoriasis (including oral retinoids, immunosuppressive/immunomodulating medication, cyclosporine, oral JAK inhibitors, or apremilast) within 4 weeks prior to baseline (Day 1).

• Participant has received any ultraviolet (UV)-B phototherapy (including tanning beds) or excimer laser within 4 weeks prior to baseline (Day 1).

• Participant has had psoralen and UV A (PUVA) treatment within 4 weeks prior to baseline (Day 1).

• Participant has received Chinese traditional medicine within 4 weeks prior to baseline (Day 1)

• Participant has received any live-attenuated vaccine, including for COVID-19, within 4 weeks prior to baseline (Day 1) or plans to receive a live-attenuated vaccine during the study and up to 4 weeks or 5 half-lives of the study drug, whichever is longer, after the last study drug administration.

• Participant is currently being treated with strong or moderate cytochrome P450 3A (CYP3A4) inhibitors, such as itraconazole or has received moderate or strong CYP3A4 inhibitors within 4 weeks prior to baseline (Day 1).

• Participant has consumed grapefruit or grapefruit juice within 1 week prior to baseline (Day 1).

• Participant has used tanning booths within 4 weeks prior to baseline (Day 1), has had excessive sun exposure, or is not willing to minimize natural and artificial sunlight exposure during the study.

• Participant is a female who is breastfeeding, pregnant, or who is planning to become pregnant during the study.

• Participant has evidence of erythrodermic, pustular, predominantly guttate psoriasis, or drug-induced psoriasis.

• Participant has any clinically significant medical condition, evidence of an unstable clinical condition, psychiatric condition, or vital signs/physical/laboratory/ECG abnormality that would, in the opinion of the investigator, put the participant at undue risk or interfere with interpretation of study results.

• Participant had a major surgery within 8 weeks prior to baseline (Day 1 or has a major surgery planned during the study.

• Participant has a history of Class III or IV congestive heart failure as defined by New York Heart Association Criteria.

• Participant has an estimated creatinine clearance of < 40 mL/min based on the Cockcroft-Gault equation or a history of renal failure.

• Participant was hospitalized in the 3 months prior to screening for asthma, has ever required intubation for treatment of asthma, currently require oral corticosteroids for the treatment of asthma, or has required more than one short-term (= 2 weeks) course of oral corticosteroids for asthma within 6 months prior to baseline (Day 1).

• Participant has a history of cancer or lymphoproliferative disease within 5 years prior to baseline (Day 1). Participants with successfully treated nonmetastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix are not to be excluded.

• Participant has a history of fever, inflammation, or systemic signs of illness suggestive of systemic or invasive infection within 4 weeks prior to baseline (Day 1).

• Participant has an active bacterial, viral, fungal, mycobacterial infection, or other infection (including TB or atypical mycobacterial disease), or any major episode of infection that required hospitalization or treatment with intravenous antibiotics within 12 weeks prior to baseline (Day 1), or oral antibiotics within 4 weeks prior to baseline (Day 1).

• Participant has a history of chronic or recurrent infectious disease, including but not limited to chronic renal infection, chronic chest infection, recurrent urinary tract infection, fungal infection (with the exception of superficial fungal infection of the nailbed), or infected skin wounds or ulcers.

• Participant has a history of an infected joint prosthesis or has received antibiotics for a suspected infection of a joint prosthesis, if that prosthesis has not been removed or replaced.

• Participant has active herpes infection, including herpes simplex 1 and 2 and herpes zoster within 8 weeks prior to Day 1.

• Participant has a history of known or suspected congenital or acquired immunodeficiency state or condition that would compromise the Participant's immune status (eg, history of splenectomy, primary immunodeficiency).

• Participant has positive results for hepatitis B surface antigens (HBsAg), antibodies to hepatitis B core antigens (anti-HBc), hepatitis C virus (HCV), or human immunodeficiency virus (HIV). Samples testing positive for HCV antibodies will require polymerase chain reaction (PCR) qualitative testing for HCV RNA.

• Participant has clinical or laboratory evidence of active or latent TB infection at screening as assessed by QuantiFERON-TB Gold (or a purified protein derivative [PPD] skin test or equivalent, or both if required per local guidelines) and chest X-ray. The PPD skin test should be utilized only when a QuantiFERON-TB Gold Test is not possible for any reason (unless local guidelines require both tests). Chest X-ray may be taken at screening or completed within 3 months prior to the screening visit, with documentation showing no evidence of infection or malignancy as read by a qualified physician.

• Participant has a known or suspected allergy to NDI-034858 or any component of the investigational product, or any other significant drug allergy (such as anaphylaxis or hepatotoxicity).

• Participant has a known history of clinically significant drug or alcohol abuse in the last year prior to baseline (Day 1).

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Psoriatic
• Psoriatic Arthritis

Intervention

Drug:
• NDI-034858
NDI-034858 oral capsule

Other:
• Placebo
NDI-034858-matching oral placebo capsule

Locations

Country	Name	City	State
Czechia	Nimbus site #XYZ	Hlucín	Ostrava-mesto
Czechia	Nimbus site #XYZ	Ostrava
Czechia	Nimbus site #XYZ	Pardubice
Czechia	Nimbus site #XYZ	Praha	Praha 3
Czechia	Nimbus site #XYZ	Uherské Hradište
Czechia	Nimbus site #XYZ	Zlin
Germany	Nimbus site #XYZ	Berlin
Germany	Nimbus site #XYZ	Berlin
Germany	Nimbus site #XYZ	Bonn	Nordrhein-Westfalen
Germany	Nimbus site #XYZ	Cologne	Nordrhein-Westfalen
Germany	Nimbus site #XYZ	Cottbus	Brandenburg
Germany	Nimbus site #XYZ	Hamburg
Germany	Nimbus site #XYZ	Hamburg
Germany	Nimbus site #XYZ	Herne	Nordrhein-Westfalen
Germany	Nimbus site #XYZ	Ratingen	Nordrhein-Westfalen
Poland	Nimbus site #XYZ	Bialystok
Poland	Nimbus site #XYZ	Bydgoszcz
Poland	Nimbus site #XYZ	Elblag	Warminsko-mazurskie
Poland	Nimbus site #XYZ	Krakow
Poland	Nimbus site #XYZ	Kraków
Poland	Nimbus site #XYZ	Kraków	Malopolskie
Poland	Nimbus site #XYZ	Lublin	Lubelskie
Poland	Nimbus site #XYZ	Nadarzyn
Poland	Nimbus site #XYZ	Nowa Sol
Poland	Nimbus site #XYZ	Poznan
Poland	Nimbus site #XYZ	Poznan
Poland	Nimbus site #XYZ	Poznan
Poland	Nimbus site #XYZ	Poznan
Poland	Nimbus site #XYZ	Sochaczew
Poland	Nimbus site #XYZ	Torun
Poland	Nimbus site #XYZ	Warszawa
Poland	Nimbus site #XYZ	Wroclaw
Poland	Nimbus site #XYZ	Wroclaw
United States	Nimbus site #XYZ	Albuquerque	New Mexico
United States	Nimbus site #XYZ	Baytown	Texas
United States	Nimbus site #XYZ	Beckley	West Virginia
United States	Nimbus site #XYZ	Charlotte	North Carolina
United States	Nimbus site #XYZ	Columbia	South Carolina
United States	Nimbus site #XYZ	Corpus Christi	Texas
United States	Nimbus site #XYZ	Duncansville	Pennsylvania
United States	Nimbus site #XYZ	Hollywood	Florida
United States	Nimbus site #XYZ	Houston	Texas
United States	Nimbus site #XYZ	Indianapolis	Indiana
United States	Nimbus site #XYZ	Jackson	Tennessee
United States	Nimbus site #XYZ	Lake Charles	Louisiana
United States	Nimbus site #XYZ	Mesquite	Texas
United States	Nimbus site #XYZ	Palm Desert	California
United States	Nimbus site #XYZ	Plantation	Florida
United States	Nimbus site #XYZ	Saint Petersburg	Florida
United States	Nimbus site #XYZ	Tampa	Florida
United States	Nimbus site #XYZ	Tampa	Florida
United States	Nimbus site #XYZ	Upland	California
United States	Nimbus site #XYZ	West Des Moines	Iowa
United States	Nimbus site #XYZ	Winter Park	Florida
United States	Nimbus site #XYZ	Worcester	Massachusetts
United States	Nimbus site #XYZ	Zephyrhills	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Takeda	Nimbus Lakshmi, Inc.

Countries where clinical trial is conducted

United States,  Czechia,  Germany,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Week 12
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.	Week 12
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.	Week 12
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.	Baseline, Week 12
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.	Baseline, Week 12
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.	Baseline, Week 12
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.	Baseline, Week 12
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.	Baseline, Week 12
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.	Baseline, Week 12
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.	Baseline, Week 12
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.	Baseline, Week 12
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.	Week 12
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.	Baseline, Week 12
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.	Week 12
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.	Week 12
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.	From first dose of study drug up to end of study (up to Week 16)
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.	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

External Links

•   To obtain more information on the study, click here/on this link