Inflammation, Rheumatoid Arthritis
Conditions
Brief summary
This trial is conducted in Europe. The aim of this clinical trial is to investigate the safety, tolerability, pharmacokinetic (the effect of the body on the investigated drug) and signs of clinical efficacy of increasing single doses or four repeated doses of NNC 0142-0002 in patients with rheumatoid arthritis.
Interventions
DRUGNNC0142-0002
Single dose, ranging from 0.0002 mg/kg up to max 7.5 mg/kg, administered subcutaneously (under the skin) on day 1
DRUGplacebo
Single dose of 0 mg/kg administered subcutaneously (under the skin); cohort 1-7b on day 1, cohort 8-11 biweekly four times
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Active rheumatoid arthritis, characterized by a Disease Activity Score (DAS28) above 3.2, and a diagnosis of at least three months duration * Aged between 18 and 75 years (both inclusive) * Subjects on stable doses of methotrexate for at least 4 weeks prior to dosing * Use of highly effective contraception during the trial (both males and females)
Exclusion criteria
* A chronic inflammatory autoimmune or joint disease other than RA (rheumatoid arthritis) * An active or latent tuberculosis * Any investigational or experimental therapy within 4 weeks or 5 half-lives (whichever is longer) prior to the screening visit * A known significant cardio-vascular disease * Vaccination against live virus or bacteria within 4 weeks prior to randomization * The use of concomitant medications that are prohibited in the trial (e.g., certain DMARDs (antirheumatic therapies that are disease modifying), biologics (here: biotechnologically produced antibodies), intra-articular corticoid-injections, etc.) * A positive test result for human immunodeficiency virus (HIV) infection, hepatitis B and/or hepatitis C, or tuberculosis skin test * Donation of greater than or equal to 400 ml of blood within 8 weeks prior to trial entry
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Adverse Events | Adverse events were collected for a mean (min; max) of 15.7 (6.4; 42.6) weeks for single-dose subjects, and 30.6 (12.7; 43.1) for multiple-dose subjects. Visits were scheduled until receptor occupancy was below the cut-off level for receptor positivity. | Adverse event: any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product, and which does not necessarily have a causal relationship with this treatment. Serious AE: AE that at any dose level resulted in any of the following: death, a life-threatening experience, in-subject hospitalization/prolongation of existing hospitalization, a persistent/significant disability/incapacity, a congenital anomaly or birth defect, or an important medical event that may jeopardize the subject and require medical or surgical intervention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve (AUC) | Data were collected from 0 hours to at least Day 43 (SD cohorts) and Day 85 (MD cohorts), and until the receptor occupancy was confirmed below the cut-off level for receptor positivity. | Systemic exposure to NNC0142-0002. |
Countries
Germany
Participant flow
Recruitment details
The trial was conducted at one site in Germany.
Pre-assignment details
A total of 65 subjects were randomised, but only 64 subjects were exposed to trial product. One subject withdrew consent after being randomised but before receiving any trial product.
Participants by arm
| Arm | Count |
|---|---|
| SD 0.0002 mg/kg Subjects were dosed once with NNC0142-0002 at a dose of 0.0002 mg/kg | 3 |
| SD 0.0012 mg/kg Subjects were dosed once with NNC0142-0002 at a dose of 0.0012 mg/kg | 3 |
| SD 0.007 mg/kg Subjects were dosed once with NNC0142-0002 at a dose of 0.007 mg/kg | 3 |
| SD 0.035 mg/kg Subjects were dosed once with NNC0142-0002 at a dose of 0.035 mg/kg | 3 |
| SD 0.175 mg/kg Subjects were dosed once with NNC0142-0002 at a dose of 0.175 mg/kg | 3 |
| SD 0.7 mg/kg Subjects were dosed once with NNC0142-0002 at a dose of 0.7 mg/kg | 3 |
| SD 2.5 mg/kg Subjects were dosed once with NNC0142-0002 at a dose of 2.5 mg/kg | 3 |
| SD 7.5 mg/kg Subjects were dosed once with NNC0142-0002 at a dose of 7.5 mg/kg | 3 |
| SD Placebo Subjects were dosed once with placebo | 8 |
| MD 0.02 mg/kg Subjects were injected biweekly four times with NNC0142-0002 at a dose of 0.02 mg/kg | 3 |
| MD 0.3 mg/kg Subjects were injected biweekly four times with NNC0142-0002 at a dose of 0.3 mg/kg | 5 |
| MD 1.0 mg/kg Subjects were injected biweekly four times with NNC0142-0002 at a dose of 1.0 mg/kg | 5 |
| MD 1.6 mg/kg Subjects were injected biweekly four times with NNC0142-0002 at a dose of 1.6 mg/kg | 5 |
| MD 4.0 mg/kg Subjects were injected biweekly four times with NNC0142-0002 at a dose of 4.0 mg/kg | 5 |
| MD Placebo Subjects were injected biweekly four times with placebo | 9 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 2 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | SD 0.0002 mg/kg | SD 0.0012 mg/kg | SD 0.007 mg/kg | SD 0.035 mg/kg | SD 0.175 mg/kg | SD 0.7 mg/kg | SD 2.5 mg/kg | SD 7.5 mg/kg | SD Placebo | MD 0.02 mg/kg | MD 0.3 mg/kg | MD 1.0 mg/kg | MD 1.6 mg/kg | MD 4.0 mg/kg | MD Placebo | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 63.0 participants STANDARD_DEVIATION 7.9 | 60.7 participants STANDARD_DEVIATION 8.1 | 66.7 participants STANDARD_DEVIATION 8.1 | 58.3 participants STANDARD_DEVIATION 5.1 | 58.7 participants STANDARD_DEVIATION 3.1 | 52.7 participants STANDARD_DEVIATION 11 | 49.0 participants STANDARD_DEVIATION 10.8 | 69.0 participants STANDARD_DEVIATION 4.6 | 52.8 participants STANDARD_DEVIATION 7.8 | 55.3 participants STANDARD_DEVIATION 5 | 56.4 participants STANDARD_DEVIATION 9.4 | 58.4 participants STANDARD_DEVIATION 5.5 | 53.0 participants STANDARD_DEVIATION 17.9 | 48.2 participants STANDARD_DEVIATION 7.7 | 53.7 participants STANDARD_DEVIATION 11 | 56.0 participants STANDARD_DEVIATION 9.8 |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 2 Participants | 3 Participants | 1 Participants | 6 Participants | 2 Participants | 5 Participants | 3 Participants | 4 Participants | 2 Participants | 8 Participants | 49 Participants |
| Sex: Female, Male Male | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 2 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 3 Participants | 1 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 3 | 1 / 3 | 2 / 3 | 1 / 3 | 3 / 3 | 1 / 3 | 3 / 3 | 3 / 3 | 1 / 3 | 6 / 8 | 4 / 5 | 4 / 5 | 5 / 5 | 3 / 5 | 8 / 9 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 1 / 3 | 0 / 3 | 1 / 3 | 0 / 8 | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 9 |
Outcome results
Primary
Frequency of Adverse Events
Adverse event: any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product, and which does not necessarily have a causal relationship with this treatment. Serious AE: AE that at any dose level resulted in any of the following: death, a life-threatening experience, in-subject hospitalization/prolongation of existing hospitalization, a persistent/significant disability/incapacity, a congenital anomaly or birth defect, or an important medical event that may jeopardize the subject and require medical or surgical intervention.
Time frame: Adverse events were collected for a mean (min; max) of 15.7 (6.4; 42.6) weeks for single-dose subjects, and 30.6 (12.7; 43.1) for multiple-dose subjects. Visits were scheduled until receptor occupancy was below the cut-off level for receptor positivity.
Population: All randomised subjects exposed to at least one dose of NNC0142-0002 or placebo.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SD 0.0002 mg/kg | Frequency of Adverse Events | Adverse events | 5 events |
| SD 0.0002 mg/kg | Frequency of Adverse Events | Serious AE | 0 events |
| SD 0.0012 mg/kg | Frequency of Adverse Events | Adverse events | 4 events |
| SD 0.0012 mg/kg | Frequency of Adverse Events | Serious AE | 0 events |
| SD 0.007 mg/kg | Frequency of Adverse Events | Adverse events | 3 events |
| SD 0.007 mg/kg | Frequency of Adverse Events | Serious AE | 0 events |
| SD 0.035 mg/kg | Frequency of Adverse Events | Adverse events | 4 events |
| SD 0.035 mg/kg | Frequency of Adverse Events | Serious AE | 0 events |
| SD 0.175 mg/kg | Frequency of Adverse Events | Serious AE | 0 events |
| SD 0.175 mg/kg | Frequency of Adverse Events | Adverse events | 1 events |
| SD 0.7 mg/kg | Frequency of Adverse Events | Serious AE | 1 events |
| SD 0.7 mg/kg | Frequency of Adverse Events | Adverse events | 8 events |
| SD 2.5 mg/kg | Frequency of Adverse Events | Adverse events | 6 events |
| SD 2.5 mg/kg | Frequency of Adverse Events | Serious AE | 0 events |
| SD 7.5 mg/kg | Frequency of Adverse Events | Adverse events | 3 events |
| SD 7.5 mg/kg | Frequency of Adverse Events | Serious AE | 1 events |
| SD Placebo | Frequency of Adverse Events | Adverse events | 9 events |
| SD Placebo | Frequency of Adverse Events | Serious AE | 0 events |
| MD 0.02 mg/kg | Frequency of Adverse Events | Serious AE | 0 events |
| MD 0.02 mg/kg | Frequency of Adverse Events | Adverse events | 4 events |
| MD 0.3 mg/kg | Frequency of Adverse Events | Adverse events | 8 events |
| MD 0.3 mg/kg | Frequency of Adverse Events | Serious AE | 0 events |
| MD 1.0 mg/kg | Frequency of Adverse Events | Serious AE | 0 events |
| MD 1.0 mg/kg | Frequency of Adverse Events | Adverse events | 13 events |
| MD 1.6 mg/kg | Frequency of Adverse Events | Serious AE | 0 events |
| MD 1.6 mg/kg | Frequency of Adverse Events | Adverse events | 10 events |
| MD 4.0 mg/kg | Frequency of Adverse Events | Adverse events | 14 events |
| MD 4.0 mg/kg | Frequency of Adverse Events | Serious AE | 0 events |
| MD Placebo | Frequency of Adverse Events | Serious AE | 0 events |
| MD Placebo | Frequency of Adverse Events | Adverse events | 9 events |
Secondary
Area Under the Concentration-time Curve (AUC)
Systemic exposure to NNC0142-0002.
Time frame: Data were collected from 0 hours to at least Day 43 (SD cohorts) and Day 85 (MD cohorts), and until the receptor occupancy was confirmed below the cut-off level for receptor positivity.
Population: All randomised subjects exposed to at least one dose of NNC0142-0002 or placebo. Serum drug concentrations after dosing with less than 0.175 mg/kg (SD cohorts) and 0.3 mg/kg (MD cohorts) were below the lower limit of quantification.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| SD 0.0002 mg/kg | Area Under the Concentration-time Curve (AUC) | NA microgram×h/mL | — |
| SD 0.0012 mg/kg | Area Under the Concentration-time Curve (AUC) | NA microgram×h/mL | — |
| SD 0.007 mg/kg | Area Under the Concentration-time Curve (AUC) | NA microgram×h/mL | — |
| SD 0.035 mg/kg | Area Under the Concentration-time Curve (AUC) | NA microgram×h/mL | — |
| SD 0.175 mg/kg | Area Under the Concentration-time Curve (AUC) | 91 microgram×h/mL | Geometric Coefficient of Variation 306.6 |
| SD 0.7 mg/kg | Area Under the Concentration-time Curve (AUC) | 4229 microgram×h/mL | Geometric Coefficient of Variation 12.7 |
| SD 2.5 mg/kg | Area Under the Concentration-time Curve (AUC) | 16616 microgram×h/mL | Geometric Coefficient of Variation 35.2 |
| SD 7.5 mg/kg | Area Under the Concentration-time Curve (AUC) | 87461 microgram×h/mL | Geometric Coefficient of Variation 29.9 |
| SD Placebo | Area Under the Concentration-time Curve (AUC) | NA microgram×h/mL | — |
| MD 0.02 mg/kg | Area Under the Concentration-time Curve (AUC) | NA microgram×h/mL | — |
| MD 0.3 mg/kg | Area Under the Concentration-time Curve (AUC) | 4034 microgram×h/mL | Geometric Coefficient of Variation 62.8 |
| MD 1.0 mg/kg | Area Under the Concentration-time Curve (AUC) | 21883 microgram×h/mL | Geometric Coefficient of Variation 29.6 |
| MD 1.6 mg/kg | Area Under the Concentration-time Curve (AUC) | 30212 microgram×h/mL | Geometric Coefficient of Variation 25.4 |
| MD 4.0 mg/kg | Area Under the Concentration-time Curve (AUC) | 83307 microgram×h/mL | Geometric Coefficient of Variation 38.3 |
| MD Placebo | Area Under the Concentration-time Curve (AUC) | NA microgram×h/mL | — |