Primary:to investigate the safety and tolerability of single and multiple doses of the study drug given by intravenous injection/infusion to patients with RAto determine the maximum tolerated dose and/or biologically effective dose of the study…
ID
Source
Brief title
Condition
- Autoimmune disorders
- Joint disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Pharmacodynamics
Pharmakinetics
Efficacy
Safety parameters
Secondary outcome
NA
Background summary
The study medication to be given is a new, investigational compound that may
eventually be used for the treatment of rheumatoid arthritis. Rheumatoid
arthritis is a long-term inflammatory disease affecting the whole body but
principally attacks the joints producing an inflammatory reaction that often
progresses to destruction of the joints. Although the cause of rheumatoid
arthritis is unknown, autoimmunity (where the body defense system does not
respond in the correct way) plays a key role in production of symptoms and
progression of the disease. In patients with rheumatoid arthritis high
concentrations of IL-6, an inflammatory marker, are found. The investigational
drug is a therapeutic antibody for the treatment of rheumatoid arthritis by
means of inhibition of the receptor for IL-6.
Study objective
Primary:
to investigate the safety and tolerability of single and multiple doses of the
study drug given by intravenous injection/infusion to patients with RA
to determine the maximum tolerated dose and/or biologically effective dose of
the study drug
Secondary:
to determine the efficacy of multiple dosing with the study drug in patients
with RA
to investigate the pharmacokinetics of the study drug after single and multiple
dosing in patients with RA
to investigate the pharmacodynamics of the study drug after single and multiple
dosing in patients with RA
to investigate the immunogenicity of the study drug after single and multiple
dosing in patients with RA
Study design
Design:
a multi-center, randomized, double-blind, placebo controlled, dose-escalation,
phase I/II study in patients with RA, consisting of a SAD part and a MAD part.
The SAD part will consist of 1 group (Group 1) of 4 (2+2) patients and up to 4
groups (Groups 2-5) of 8 (6+2) patients each. In each group, as of the second
group, 6 patients will receive a single intravenous (iv) dose of the study drug
and 2 patients will receive a single iv dose of placebo.
Procedures and assessments
clinical laboratory, vital signs (including oral body temperature), physical
examination, body weight, abdominal ultrasound, ACR classification of
functional capacity and DAS 28, 12-lead ECG, pregnancy test (females only); at
eligibility screening: medical history, body height, chest X-ray, Quantiferon
test for active tubercolosis, blood sampling for PD biomarkers, blood sampling
for immunogenicity assessment, , alcohol and drug screen, HBsAg, anti HCV,
anti-HIV 1/2; alcohol and drug screen, pregnancy test (females only),
immunogenicity assessment, ACR classification of functional capacity and ACR
assessment of criteria for ACR response, DAS28 score, disease activity VAS and
HAQ to be repeated upon admission
Observation period
one period in clinic from Day -1 up to 48 h or 72 h (based on the judgement of
the Investigator) after drug administration on Day 1 and ambulatory visits on
Days 4, 5, 8, 15, 29, 36, 57 and follow-up
Blood sampling
for pharmacokinetics of ALX-0061 in plasma: pre-dose and at end of
injection/infusion and 8 h post-dose and once on Days 2, 3, 4, 5, 8, 15, 29,
36, 57 and once at follow-up
for pharmacodynamic parameters (CRP, ESR and fibrinogen, IL-6, sIL-6R, TNF-*,
IL-1* and IFN-*: pre-dose and 8 h post-dose and once on Days 2, 3, 4, 8, 15,
29, 36, 57 and once at follow-up
for immunogenicity: pre-dose and once on Days 8, 15, 29 and 57 and once at
follow-up
Efficacy assessments
ACR reponse, DAS 28 score, EULAR response, disease activity VAS and HQ: once on
Day 57
Safety assessments
Adverse events: throughout the study; vital signs pre-dose and 1, 2, 4 and 8 h
post-dose and once on Days 3, 4, 8, 15, 29, 36 and 57; 12-lead ECG: pre-dose
and 2 and 8 h post-dose and once on Days 8, 15, 29, 36 and 57; clinical
laboratory: pre-dose and once on Days 8, 15, 29, 36 and 57
Bioanalysis
analysis of serum ALX-0061 samples using a validated method by Sponsor
analysis of serum anti-ALX-0061 antibodies samples using a validated method by
Sponsor
analysis of CRP, ESR and fibrinogen using a clinical chemistry method by PRA
analysis of serum SAA samples using a validated method by PRA
analysis of serum IL-6 samples using a validated method by PRA
analysis of serum TNF-*, IL-1* and IFN-* samples using validate methods by PRA
Intervention
Active substance: ALX-0061
Activity: anti-interleukin-6 receptor (IL-6R) nanobody inhibitor
Indication: rheumatoid arthritis
Dosage form: solution for injection/infusion
Study burden and risks
Procedures: pain, light bleeding, haematoma, possibly an infection.
Technologiepark 21
B-9052 Zwijnaarde
BE
Technologiepark 21
B-9052 Zwijnaarde
BE
Listed location countries
Age
Inclusion criteria
1. Gender: male and female
2. Age: 18-80 years, inclusive
3. Body mass index (BMI): <35.0 kg/m2
4. Diagnosed with RA according to the 2010 European League Against Rheumatism (EULAR)/ American College of Rheumatology (ACR) criteria for at least 6 months prior to randomization
5. Inadequate response or intolerance to disease modifying antirheumatic drugs (DMARDs) (including methotrexate [MTX]). Treatment with MTX for at least 12 weeks prior to screening, with at least 4 weeks before screening at a stable dose, that will remain stable throughout the study period
6. DAS28 ><= 2.4
Exclusion criteria
1. A documented history of an autoimmune disease other than RA (other than secondary Sjögren*s syndrome)
2. Functional class IV by ACR classification
3. Any new/additional biologic DMARD therapy, cytotoxic drugs and immunosuppressants within four weeks prior to screening, and between screening and Day 1 with the exception of ALX-0061
4. Suspicion of active tuberculosis verified by quantiferon test and abnormal chest X-ray
5. Female patients who are pregnant during the study, or are breastfeeding
6. History of anaphylactic reactions to protein therapeutics
7. Participation in an investigational drug study within 60 days prior to drug administration except for the patients who participated in the SAD part of this study and who are eligible to participate in the MAD part
8. Donation of more than 300 mL of blood within 60 days prior to drug administration
9. Malignancy, or prior malignancy, with a disease free interval of <5 years after diagnosis and intervention except curative treatment for non-melanoma skin cancer or resected carcinoma in situ
10. Any current or recent (within 4 weeks prior to first dose) signs or symptoms of infection that requires parenteral antibiotic administration, any known active viral infection (hepatitis B virus [HBV], hepatitis C virus [HCV], human immunodeficiency virus [HIV]) that would impair the participation in the study
11. Major surgery (including joint surgery) within 8 weeks prior to screening and hospitalization for a clinically relevant event within the 4 weeks prior to screening
12. Any other disease, metabolic dysfunction, physical examination finding, or clinically significant laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk for treatment complications
13. Administration of a live, attenuated vaccine within 1 month before dosing with ALX-0061, or anticipation that such a live attenuated vaccine will be required during the study or within 60 days after the last dose
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2010-022865-81-NL |
| CCMO | NL34944.056.10 |