Clinical trial NCT05153148: A Study to Evaluate the Efficacy, Safety, and Tolerability of NDI-034858 in Participants With Active Psoriatic Arthritis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Psoriatic Arthritis
Keywords: Placebo-Controlled
Double-blind
Multiple-dose study
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Nimbus Lakshmi, Inc.
First posted: 2021-12-10
Enrollment: 305
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Percentage of Participants Who Achieved at Least an American College of Rheumatology 20 (ACR20) Response at Week 12
timeFrame: Week 12
Secondary outcomes:
measure: Percentage of Participants Who Achieved at Least an ACR-50 Response at Week 12
timeFrame: Week 12
measure: Percentage of Participants Who Achieved at Least an ACR-70 Response at Week 12
timeFrame: Week 12
measure: Change From Baseline in Tender Joint Count (TJC) at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Swollen Joint Count (SJC) at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in PGA-PsA at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in PGAAP at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in PhGA-PsA at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in HAQ-DI Total Score at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Dactylitis Count (DC) at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Leeds Enthesitis Index (LEI) at Week 12
timeFrame: Baseline, Week 12
measure: Percentage of Participants With Minimal Disease Activity (MDA) Response at Week 12
timeFrame: Week 12
measure: Change From Baseline in Disease Activity Index for Psoriatic Arthritis (DAPSA) at Week 12
timeFrame: Baseline, Week 12
measure: Percentage of Participants Who Achieved PASI-75 Response at Week 12
timeFrame: Week 12
measure: 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
timeFrame: Week 12
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)
timeFrame: From first dose of study drug up to end of study (up to Week 16)
measure: Plasma Concentration of NDI-034858
timeFrame: 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
Other outcomes:
Locations:
city: Palm Desert
country: United States
facility: Nimbus site #XYZ
state: California
city: Upland
country: United States
facility: Nimbus site #XYZ
state: California
city: Hollywood
country: United States
facility: Nimbus site #XYZ
state: Florida
city: Plantation
country: United States
facility: Nimbus site #XYZ
state: Florida
city: Saint Petersburg
country: United States
facility: Nimbus site #XYZ
state: Florida
city: Tampa
country: United States
facility: Nimbus site #XYZ
state: Florida
city: Tampa
country: United States
facility: Nimbus site #XYZ
state: Florida
city: Winter Park
country: United States
facility: Nimbus site #XYZ
state: Florida
city: Zephyrhills
country: United States
facility: Nimbus site #XYZ
state: Florida
city: Indianapolis
country: United States
facility: Nimbus site #XYZ
state: Indiana
city: West Des Moines
country: United States
facility: Nimbus site #XYZ
state: Iowa
city: Lake Charles
country: United States
facility: Nimbus site #XYZ
state: Louisiana
city: Worcester
country: United States
facility: Nimbus site #XYZ
state: Massachusetts
city: Albuquerque
country: United States
facility: Nimbus site #XYZ
state: New Mexico
city: Charlotte
country: United States
facility: Nimbus site #XYZ
state: North Carolina
city: Duncansville
country: United States
facility: Nimbus site #XYZ
state: Pennsylvania
city: Columbia
country: United States
facility: Nimbus site #XYZ
state: South Carolina
city: Jackson
country: United States
facility: Nimbus site #XYZ
state: Tennessee
city: Baytown
country: United States
facility: Nimbus site #XYZ
state: Texas
city: Corpus Christi
country: United States
facility: Nimbus site #XYZ
state: Texas
city: Houston
country: United States
facility: Nimbus site #XYZ
state: Texas
city: Mesquite
country: United States
facility: Nimbus site #XYZ
state: Texas
city: Beckley
country: United States
facility: Nimbus site #XYZ
state: West Virginia
city: Hlučín
country: Czechia
facility: Nimbus site #XYZ
state: Ostrava-město
city: Praha
country: Czechia
facility: Nimbus site #XYZ
state: Praha 3
city: Ostrava
country: Czechia
facility: Nimbus site #XYZ
city: Pardubice
country: Czechia
facility: Nimbus site #XYZ
city: Uherské Hradiště
country: Czechia
facility: Nimbus site #XYZ
city: Zlin
country: Czechia
facility: Nimbus site #XYZ
city: Cottbus
country: Germany
facility: Nimbus site #XYZ
state: Brandenburg
city: Bonn
country: Germany
facility: Nimbus site #XYZ
state: Nordrhein-Westfalen
city: Cologne
country: Germany
facility: Nimbus site #XYZ
state: Nordrhein-Westfalen
city: Herne
country: Germany
facility: Nimbus site #XYZ
state: Nordrhein-Westfalen
city: Ratingen
country: Germany
facility: Nimbus site #XYZ
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: Nimbus site #XYZ
city: Berlin
country: Germany
facility: Nimbus site #XYZ
city: Hamburg
country: Germany
facility: Nimbus site #XYZ
city: Hamburg
country: Germany
facility: Nimbus site #XYZ
city: Lublin
country: Poland
facility: Nimbus site #XYZ
state: Lubelskie
city: Kraków
country: Poland
facility: Nimbus site #XYZ
state: Malopolskie
city: Elblag
country: Poland
facility: Nimbus site #XYZ
state: Warminsko-mazurskie
city: Bialystok
country: Poland
facility: Nimbus site #XYZ
city: Bydgoszcz
country: Poland
facility: Nimbus site #XYZ
city: Krakow
country: Poland
facility: Nimbus site #XYZ
city: Kraków
country: Poland
facility: Nimbus site #XYZ
city: Nadarzyn
country: Poland
facility: Nimbus site #XYZ
city: Nowa Sol
country: Poland
facility: Nimbus site #XYZ
city: Poznan
country: Poland
facility: Nimbus site #XYZ
city: Poznan
country: Poland
facility: Nimbus site #XYZ
city: Poznań
country: Poland
facility: Nimbus site #XYZ
city: Poznań
country: Poland
facility: Nimbus site #XYZ
city: Sochaczew
country: Poland
facility: Nimbus site #XYZ
city: Torun
country: Poland
facility: Nimbus site #XYZ
city: Warszawa
country: Poland
facility: Nimbus site #XYZ
city: Wroclaw
country: Poland
facility: Nimbus site #XYZ
city: Wroclaw
country: Poland
facility: Nimbus site #XYZ
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References: