CompletedPhase 2

Study to Assess the Safety, Pharmacokinetics, and Efficacy of KPL-404 in Participants With Rheumatoid Arthritis With Inadequate Response or Intolerance to at Least One Biologic Disease-modifying Anti-rheumatic Drug or a Janus Kinase Inhibitor

United States145 participantsStarted 2021-12-14

Plain-language summary

Phase 2 study of the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy of KPL-404 in subjects with moderate to severe Rheumatoid Arthritis.

Who can participate

Age range18 Years – 80 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

✓. The following csDMARDs are allowed: oral or parenteral methotrexate (\[MTX\]; 7.5 to 25 mg/week), sulfasalazine (≤ 3000 mg/day), hydroxychloroquine (≤ 400 mg/day), chloroquine (≤ 250 mg/day), and leflunomide (≤ 20 mg/day).
✓. A combination of up to 2 background csDMARDs is allowed, except the combination of MTX and leflunomide.
✓. Six or more swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts) at screening and baseline visits;
✓. Level of high-sensitivity C-reactive protein ≥ 3 mg/L (by central laboratory);
✓. Documented seropositivity for serum Rheumatoid Factor (RF) and/or Anti-citrullinated protein antibody (ACPA) (\>ULN) at screening or by prior laboratory evaluation.
✓. ≥ 4 weeks for etanercept;
✓. ≥ 8 weeks for adalimumab, infliximab, certolizumab, golimumab, abatacept, tocilizumab, and sarilumab;
✓. ≥ 1 year for rituximab;

Exclusion criteria

✕. Moderate to severe congestive heart failure (New York Heart Association class III or IV);
✕. Recent (within past 6 months) cerebrovascular accident, myocardial infarction, coronary stenting;
✕. Uncontrolled hypertension as defined by a confirmed systolic blood pressure \> 160 mmHg or diastolic blood pressure \> 100 mmHg.

What they're measuring

Cohorts 1 and 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

Timeframe: From first dose of study drug to 24 weeks

Cohorts 1 and 2: Maximum Serum Concentration (Cmax)

Timeframe: Days 1 (Dose 1) and 57 (Dose 4)

Cohorts 1 and 2: Area Under the Serum Concentration-time Curve From Time of Administration to the End of the Dosing Interval, (AUCtau)

Timeframe: Days 1 (Dose 1) and 57 (Dose 4)

Cohort 3 and 4: Change From Baseline in Disease Activity Score of 28 Joints Using C-reactive Protein (DAS28-CRP) at Week 12

Timeframe: Baseline, Week 12

Trial details

NCT IDNCT05198310

SponsorKiniksa Pharmaceuticals, Ltd.

Sponsor typeINDUSTRY

Study typeINTERVENTIONAL

Primary completion2024-02-08

Results submitted2025-07-02

View on ClinicalTrials.gov More Arthritis, Rheumatoid trials

Who can participate

Age range18 Years – 80 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

✓. The following csDMARDs are allowed: oral or parenteral methotrexate (\[MTX\]; 7.5 to 25 mg/week), sulfasalazine (≤ 3000 mg/day), hydroxychloroquine (≤ 400 mg/day), chloroquine (≤ 250 mg/day), and leflunomide (≤ 20 mg/day).
✓. A combination of up to 2 background csDMARDs is allowed, except the combination of MTX and leflunomide.
✓. Six or more swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts) at screening and baseline visits;
✓. Level of high-sensitivity C-reactive protein ≥ 3 mg/L (by central laboratory);
✓. Documented seropositivity for serum Rheumatoid Factor (RF) and/or Anti-citrullinated protein antibody (ACPA) (\>ULN) at screening or by prior laboratory evaluation.
✓. ≥ 4 weeks for etanercept;
✓. ≥ 8 weeks for adalimumab, infliximab, certolizumab, golimumab, abatacept, tocilizumab, and sarilumab;
✓. ≥ 1 year for rituximab;

Exclusion criteria

✕. Moderate to severe congestive heart failure (New York Heart Association class III or IV);
✕. Recent (within past 6 months) cerebrovascular accident, myocardial infarction, coronary stenting;
✕. Uncontrolled hypertension as defined by a confirmed systolic blood pressure \> 160 mmHg or diastolic blood pressure \> 100 mmHg.

What they're measuring

Cohorts 1 and 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

Timeframe: From first dose of study drug to 24 weeks

Cohorts 1 and 2: Maximum Serum Concentration (Cmax)

Timeframe: Days 1 (Dose 1) and 57 (Dose 4)

Cohorts 1 and 2: Area Under the Serum Concentration-time Curve From Time of Administration to the End of the Dosing Interval, (AUCtau)

Timeframe: Days 1 (Dose 1) and 57 (Dose 4)

Cohort 3 and 4: Change From Baseline in Disease Activity Score of 28 Joints Using C-reactive Protein (DAS28-CRP) at Week 12

Timeframe: Baseline, Week 12