Primary objective: Safety and tolerability of repeated subcutaneous injections of MT203 in patients with mild to moderate RA.Secondary objectives: Pharmacokinetics, pharmacodynamics, including explorative biomarker assessments and efficacy of…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Not applicable: this is a mainly a safety and efficacy study (phase Ib), please
refer to the study objectives.
Secondary outcome
Not applicable; see primary endpoints.
Background summary
Rheumatoid arthritis (RA) is a chronic destructive disease characterized by
joint inflammation leading to erosions of articular cartilage and subchondral
bone.Granulocyte macrophage colony stimulating factor (GM-CSF) is thought to be
a key activator of the innate arm of the immune system and as such is involved
in chronic stages of inflammatory and autoimmune diseases where macrophages,
neutrophils, granulocytes, eosinophils and dendritic cells contribute to
disease progression. MT203 is a human IgG1 monoclonal antibody potently and
specifically neutralizing GM-CSF. It shows promise for the treatment of
autoimmune diseases, such as RA. MT203 appears to be generally safe and
well-tolerated.
Study objective
Primary objective: Safety and tolerability of repeated subcutaneous injections
of MT203 in patients with mild to moderate RA.
Secondary objectives: Pharmacokinetics, pharmacodynamics, including explorative
biomarker assessments and efficacy of repeated subcutaneous injections of MT203
in patients with mild to moderate RA.
Study design
This is a phase Ib, double-blind, placebo-controlled, randomized,
dose-escalating study in approximately 24 subjects in The Netherlands and
Bulgaria.
Intervention
Repeated subcutaneous injections of MT203 or placebo, every 14 days (in total 3
doses per patient).
Study burden and risks
Although a first-in-man trial has been performed, the following potential risks
cannot be excluded yet: allergic reaction, local pain, haematoma, or a
superficial thrombophlebitis, Pulmonary Alveolar Proteinosis (PAP), mild and
transient increase in serum transaminase activity levels (ALAT, ASAT) and in
serum CRP levels.
As MT203 is expected to have immunomodulatory effects the potential risk of
increased infection rates needs to be considered. To safeguard the patients,
medical history and signs indicative of predisposition to or presence of
underlying latent or incipient infections will be checked during screening and
patients having these signs excluded. Patients will be excluded from
participation in the trial in case of a positive test or other clinical
evidence of tuberculosis.
Langebjerg 1
Roskilde 4000
DK
Langebjerg 1
Roskilde 4000
DK
Listed location countries
Age
Inclusion criteria
1. Out-patients with active RA with low to moderate disease activity (DAS28 >= 2.6 and <= 5.1).
2. Patients must be on stable doses of MTX >= 7.5 and <= 25 mg/week for at least 12 weeks before the first injection of IMP, with appropriate folic acid supplementation.
3. Age >= 18 years at screening.
4. Body weight >= 50 kg at screening; BMI >= 18.0 and <= 30.0 kg/m2 at screening.
Exclusion criteria
1. The use of any medication, including local injections with gold or corticosteroids, over-the-counter medication and prescription anti-rheumatic naturopathic medicines/phytopharmaca ("herbs") with immunomodulatory effect, except for the allowed concomitant medication, within 2 weeks, or within less than 10 times the half-life of the respective drug, or within the duration of its pharmacodynamic effect before the first injection (whichever is longer), as well as the anticipated use of disallowed concomitant medication between the first injection and EoT/ET visit.
2. Previous use of any GM-CSF treatment and/or any treatment antagonising GM-CSF or its receptor at any time in the past.
3. The use of biological agents (as experimental therapy or not) within (whichever is longer):
- 10 times the respective half-life before the first injection of trial medication.
- the continuation of the pharmacodynamic effects of the respective agent before the first injection of trial medication.
- 3 months before the first injection of trial medication in case of TNF inhibitors.
- 12 months for any cell depleting therapies (after B-cell depleting therapy, B-cells must have returned to normal values before screening).
4. The use of the oral DMARD leflunomide within 12 weeks before the first injection of trial medication, or within 4 weeks before first injection of trial medication if supportive oral cholestyramine (>= 8 g/tid) or charcoal (>=50g/qds) washout treatment is/was given.
5. Chronic use of prophylactic or suppressive antibiotic, antifungal or antiviral agents.
6. The use of intra-muscular, intravenous or intra-articular corticosteroids within 4 weeks before the first injection of trial medication.
Design
Recruitment
Medical products/devices used
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 | EUCTR2010-018502-36-NL |
| CCMO | NL33507.058.10 |