First-in-man Trial of NNC0142-0002 in Patients With Rheumatoid Arthritis

Study Overview
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Brief Summary
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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.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Dose-escalation, Single and Multiple Dose Trial to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of NNC0142-0002 Administered Subcutaneously to Subjects With Rheumatoid Arthritis

Conditions
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Inflammation, Rheumatoid Arthritis

Intervention / Treatment
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* Drug: NNC0142-0002
* Drug: NNC0142-0002
* Drug: NNC0142-0002
* Drug: NNC0142-0002
* Drug: NNC0142-0002
* Drug: NNC0142-0002
* Drug: NNC0142-0002
* Drug: NNC0142-0002
* Drug: placebo
* Drug: NNC0142-0002
* Drug: NNC0142-0002
* Drug: NNC0142-0002
* Drug: NNC0142-0002
* Drug: NNC0142-0002
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SD 0.0002 mg/kg<br>Subjects were injected once with NNC0142-0002 at a dose of 0.0002 mg/kg | Drug: NNC0142-0002<br>* Single dose, ranging from 0.0002 mg/kg up to max 7.5 mg/kg, administered subcutaneously (under the skin) on day 1<br>|
| Experimental: SD 0.0012 mg/kg<br>Subjects were injected once with NNC0142-0002 at a dose of 0.0012 mg/kg | Drug: NNC0142-0002<br>* Single dose, ranging from 0.0002 mg/kg up to max 7.5 mg/kg, administered subcutaneously (under the skin) on day 1<br>|
| Experimental: SD 0.007 mg/kg<br>Subjects were injected once with NNC0142-0002 at a dose of 0.007 mg/kg | Drug: NNC0142-0002<br>* Single dose, ranging from 0.0002 mg/kg up to max 7.5 mg/kg, administered subcutaneously (under the skin) on day 1<br>|
| Experimental: SD 0.035 mg/kg<br>Subjects were injected once with NNC0142-0002 at a dose of 0.035 mg/kg | Drug: NNC0142-0002<br>* Single dose, ranging from 0.0002 mg/kg up to max 7.5 mg/kg, administered subcutaneously (under the skin) on day 1<br>|
| Experimental: SD 0.175 mg/kg<br>Subjects were injected once with NNC0142-0002 at a dose of 0.175 mg/kg | Drug: NNC0142-0002<br>* Single dose, ranging from 0.0002 mg/kg up to max 7.5 mg/kg, administered subcutaneously (under the skin) on day 1<br>|
| Experimental: SD 0.7 mg/kg<br>Subjects were injected once with NNC0142-0002 at a dose of 0.7 mg/kg | Drug: NNC0142-0002<br>* Single dose, ranging from 0.0002 mg/kg up to max 7.5 mg/kg, administered subcutaneously (under the skin) on day 1<br>|
| Experimental: SD 2.5 mg/kg<br>Subjects were injected once with NNC0142-0002 at a dose of 2.5 mg/kg | Drug: NNC0142-0002<br>* Single dose, ranging from 0.0002 mg/kg up to max 7.5 mg/kg, administered subcutaneously (under the skin) on day 1<br>|
| Experimental: SD 7.5 mg/kg<br>Subjects were injected once with NNC0142-0002 at a dose of 7.5 mg/kg | Drug: NNC0142-0002<br>* Single dose, ranging from 0.0002 mg/kg up to max 7.5 mg/kg, administered subcutaneously (under the skin) on day 1<br>|
| Experimental: SD Placebo<br>Subjects were injected once with placebo | Drug: placebo<br>* Single dose of 0 mg/kg administered subcutaneously (under the skin); cohort 1-7b on day 1, cohort 8-11 biweekly four times<br>|
| Experimental: MD 0.02 mg/kg<br>Subjects were injected biweekly four times with NNC0142-0002 at a dose of 0.02 mg/kg | Drug: NNC0142-0002<br>* Multiple dose, ranging from 0.02 mg/kg up to max 4.0 mg/kg, administered subcutaneously (under the skin) four times biweekly<br>|
| Experimental: MD 0.3 mg/kg<br>Subjects were injected biweekly four times with NNC0142-0002 at a dose of 0.3 mg/kg | Drug: NNC0142-0002<br>* Multiple dose, ranging from 0.02 mg/kg up to max 4.0 mg/kg, administered subcutaneously (under the skin) four times biweekly<br>|
| Experimental: MD 1.0 mg/kg<br>Subjects were injected biweekly four times with NNC0142-0002 at a dose of 1.0 mg/kg | Drug: NNC0142-0002<br>* Multiple dose, ranging from 0.02 mg/kg up to max 4.0 mg/kg, administered subcutaneously (under the skin) four times biweekly<br>|
| Experimental: MD 1.6 mg/kg<br>Subjects were injected biweekly four times with NNC0142-0002 at a dose of 1.6 mg/kg | Drug: NNC0142-0002<br>* Multiple dose, ranging from 0.02 mg/kg up to max 4.0 mg/kg, administered subcutaneously (under the skin) four times biweekly<br>|
| Experimental: MD 4.0 mg/kg<br>Subjects were injected biweekly four times with NNC0142-0002 at a dose of 4.0 mg/kg | Drug: NNC0142-0002<br>* Multiple dose, ranging from 0.02 mg/kg up to max 4.0 mg/kg, administered subcutaneously (under the skin) four times biweekly<br>|
| Experimental: MD Placebo<br>Subjects were injected biweekly four times with placebo | Drug: placebo<br>* Single dose of 0 mg/kg administered subcutaneously (under the skin); cohort 1-7b on day 1, cohort 8-11 biweekly four times<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Concentration-time Curve (AUC) | Systemic exposure to NNC0142-0002. | 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. |