Safety and Tolerability of Anti-IL-20 in Healthy Volunteers and 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 and tolerability of single doses of Anti-IL-20 in healthy volunteers (HV) and patients with rheumatoid arthritis (RA).

Official Title
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A Randomised, Double-blind, Placebo-controlled, Single- Dose, Dose-escalation Trial of Anti-IL-20 in Healthy Volunteers and Patients With Rheumatoid Arthritis

Conditions
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Inflammation, Rheumatoid Arthritis, Healthy

Intervention / Treatment
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* Drug: anti-IL-20
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For healthy volunteers (HV) the following applies: Subjects who are considered to be generally healthy based on assessment of medical history, physical examination and clinical laboratory data at screening, as judged by the Investigator Females who are post-menopausal, surgically sterile or of non-child-bearing potential For rheumatoid arthritis (RA) patients the following applies: A diagnosis of rheumatoid arthritis according to the American College of Rheumatology (ACR1987 classification) of at least three months' duration prior to dosing Active RA, characterised by a Disease Activity Score 28 (DAS28) greater than 3.2 Methotrexate treatment (stable doses of maximally 25.0 mg/week for at least 4 weeks) and concomitant intake of folic acid 1 mg/day or 5 mg/week Females who are post-menopausal, surgically sterile or of non-child-bearing potential Exclusion Criteria: For healthy volunteers (HV) the following applies: Male subjects who do not accept to use double barrier methods of birth control from first dosing until 3 moths after their last visit Body mass index (BMI) below 18.5 or above 35.0 kg/m2 Clinically significant cardiac or cardiovascular disease Abnormal blood pressure and heart rate Hepatic insufficiency Renal insufficiency Positive for humane immunodeficiency virus (HIV) Positive for hepatitis B (HBV) or hepatitis C (HCV) Lymphoproliferative disease History or signs of malignancy (except adequately treated and cured basal or squamous cell carcinoma of the skin or cervical carcinoma in situ occurring more than 12 months prior to dosing) History of any autoimmune or current inflammatory conditions including rheumatoid arthritis or any other joint disease Active or latent tuberculosis: For tuberculosis unvaccinated subjects detected as a positive Mantoux test. For subjects vaccinated against tuberculosis detected as a positive QuantiFeron-test Chronic or ongoing infectious disease requiring systemic anti-infectious treatment within the last 2 weeks prior to administration of trial drug Any vaccination within the last month before dosing Known active viral, bacterial or fungal infection, including herpes, herpes zoster or cold sores 14 days prior to dosing Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within 2 weeks prior to dosing, unless in the opinion of the Investigator the medication will not interfere with the trial procedures or compromise the safety of the subject History of or current drug and/or alcohol abuse Blood donation within the last 3 months (more than 0.45 L) For rheumatoid arthritis (RA) patients the following applies: Male subjects who do not accept to use double barrier methods of birth control from first dosing until 3 months after their last visit Body mass index (BMI) below 18.5 or above 35.0 kg/m2 Subjects with chronic inflammatory autoimmune disease other than rheumatoid arthritis (except secondary Sjögren's syndrome) History of or current inflammatory joint disease other than rheumatoid arthritis (e.g. gout, psoriatic or reactive arthritis, Lyme's disease, juvenile arthritis) Chronic or ongoing infectious disease requiring systemic anti-infectious treatment within the last 2 weeks prior to dosing Any vaccination within the last month before dosing Known active viral, bacterial or fungal infection, including herpes, herpes zoster or cold sores 14 days prior to administration of trial product Lymphoproliferative disease History or signs of malignancy (except adequately treated and cured basal or squamous cell carcinoma of the skin or cervical carcinoma in situ occurring more than 12 months prior to dosing) Use of selective cyclooxygenase-2 (COX-2) inhibitors within the last 2 weeks prior to randomisation Concomitant medication

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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Accepts Healthy Volunteers

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: A, HV<br>Dose cohort 1 (3 subjects active, 1 placebo) | Drug: anti-IL-20<br>* Single s.c. injection (per dose cohort)<br>* Other names: NN8226;Drug: placebo<br>* Single s.c. injection (per dose cohort)<br>* Other names: NN8226;|
| Experimental: B, HV<br>Dose cohort 2 (3 subjects active, 1 placebo) | Drug: anti-IL-20<br>* Single s.c. injection (per dose cohort)<br>* Other names: NN8226;Drug: placebo<br>* Single s.c. injection (per dose cohort)<br>* Other names: NN8226;|
| Experimental: C, HV<br>Dose cohort 3 (3 subjects active, 1 placebo) | Drug: anti-IL-20<br>* Single s.c. injection (per dose cohort)<br>* Other names: NN8226;Drug: placebo<br>* Single s.c. injection (per dose cohort)<br>* Other names: NN8226;|
| Experimental: D, HV<br>Dose cohort 4 (3 subjects active, 1 placebo) | Drug: anti-IL-20<br>* Single s.c. injection (per dose cohort)<br>* Other names: NN8226;Drug: placebo<br>* Single s.c. injection (per dose cohort)<br>* Other names: NN8226;|
| Experimental: E, HV<br>Dose cohort 5 (3 subjects active, 1 placebo) | Drug: anti-IL-20<br>* Single s.c. injection (per dose cohort)<br>* Other names: NN8226;Drug: placebo<br>* Single s.c. injection (per dose cohort)<br>* Other names: NN8226;|
| Experimental: A, RA<br>Dose cohort 1 (3 subjects active, 1 placebo) | Drug: anti-IL-20<br>* Single s.c. injection (per dose cohort)<br>* Other names: NN8226;Drug: placebo<br>* Single s.c. injection (per dose cohort)<br>* Other names: NN8226;|
| Experimental: B, RA<br>Dose cohort 2 (3 subjects active, 1 placebo) | Drug: anti-IL-20<br>* Single s.c. injection (per dose cohort)<br>* Other names: NN8226;Drug: placebo<br>* Single s.c. injection (per dose cohort)<br>* Other names: NN8226;|
| Experimental: C, RA<br>Dose cohort 3 (3 subjects active, 1 placebo) | Drug: anti-IL-20<br>* Single s.c. injection (per dose cohort)<br>* Other names: NN8226;Drug: placebo<br>* Single s.c. injection (per dose cohort)<br>* Other names: NN8226;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events, including injection site tolerability |  | during treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Terminal serum half-life (t½) |  | during treatment | 
| Maximum observed serum concentration (Cmax) |  | during treatment | 
| Time to reach maximum serum concentration (tmax) |  | during treatment | 
| Area under the serum concentration-time curve (AUC0-t and AUC) |  | during treatment | 
| Relevant biomarkers in serum and plasma, as well as synovial fluid (if applicable) |  | during treatment |