Clinical trial NCT01317797: A Trial to Evaluate the Safety and Tolerability of Namilumab (MT203) in Patients With Mild to Moderate Rheumatoid Arthritis
Official title: A Phase Ib Double-blind, Placebo-controlled, Randomized, Dose-escalating Trial to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of Repeated Subcutaneous Injections of MT203 in Patients With Mild to Moderate Rheumatoid Arthritis on Treatment With Methotrexate
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis
MT203
Human IgG1 monoclonal antibody
GM-CSF monoclonal antibody
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2011-03-17
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this trial is primarily to investigate the safety and tolerability of repeated subcutaneous injections of MT203 in patients with mild to moderate rheumatoid arthritis. Furthermore, the amount of MT203 in the blood will be measured and it will be investigated how the body responds to MT203 treatment and if MT203 is effective in the treatment of rheumatoid arthritis.

Detailed description: The trial medication will be administered at 2 dose levels as subcutaneous injections. Each patient will receive three injections in total. The trial duration consists of a screening period (28 - 2 days prior to the first injection) and a treatment and observation period (4 months). The trial requires approximately 20 visits at the study site.

Eligibility criteria: Inclusion Criteria:

1. Out-patients with active rheumatoid arthritis (RA), according to the ACR 1987 revised criteria, with low to moderate disease activity (DAS28-ESR ≥ 2.6 and ≤ 5.1)
2. Patients must be on stable doses of methotrexate (MTX) ≥ 7.5 and ≤ 25 mg/week for at least 12 weeks before the first injection, with appropriate folic acid supplementation
3. Age ≥ 18 years at Screening
4. Body weight at least 50 kg at Screening; BMI: ≥ 18.0 and ≤ 30.0 kg/m2 at Screening
5. Negative tuberculosis test at Screening
6. Heterosexually active male and female patients of childbearing potential are obliged to follow whatever contraceptive and / or breastfeeding restrictions may be required for their concomitant medication(s), including methotrexate.

In addition, heterosexually active male and female patients of childbearing potential are required to use effective double-method contraception (one hormonal contraceptive or intrauterine device and one other additional contraceptive method) for 1 month before the first administration of the IMP, during the course of the trial, and for 6 month after the last injection of MT203.

No special requirements are made for female patients proven to be post-menopausal (at least 2 years after last menstrual period and FSH ≥ 40IU/L), surgically sterilized or hysterectomized. Likewise no special requirements for heterosexually active male who are surgical sterilized.

Pregnant or lactating female patients have to be excluded.

Exclusion Criteria:

1. Participation in another clinical trial or previous dosing in this trial
2. Use of specified medications within certain timeframes or use of certain comedications
3. History or presence of specified diseases
4. Drug abuse
5. Certain laboratory parameters outside a specified range
6. Donation of blood
7. Relevant decrease in lung function
8. Infections, frequent or chronic infections, herpes zoster
9. Females: positive pregnancy test
10. Presence of history of tuberculosis
11. History of malignancy

Primary outcomes:
measure: Number of Participants With Clinically Significant Clinical Laboratory Results
timeFrame: From Day 1 Up to Day 118
measure: Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings
timeFrame: From Day 1 Up to Day 118
measure: Number of Participants With Clinically Significant Vital Signs
timeFrame: From Day 1 Up to Day 118
measure: Number of Participants With Clinically Significant Pulmonary Function Tests
timeFrame: From Day 1 Up to Day 118
measure: Number of Participants With Clinically Significant Physical Examination Findings
timeFrame: From Day 1 Up to Day 118
measure: Number of Participants Reporting One or More Treatment Emergent Adverse Events
timeFrame: From Day 1 Up to Day 118
Secondary outcomes:
measure: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MT203
timeFrame: Day 1 and 29 (Pre-dose and 2 and 6 hours post-dose)
measure: Cmax: Maximum Observed Plasma Concentration for MT203
timeFrame: Day 1 and 29 (Pre-dose and 2 and 6 hours post-dose)
measure: AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for MT203
timeFrame: Day 1 and 29 (Pre-dose and 2 and 6 hours post-dose)
measure: AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for MT203
timeFrame: Day 29 (Pre-dose and 2 and 6 hours post-dose)
measure: AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for MT203
timeFrame: Day 29 (Pre-dose and 2 and 6 hours post-dose)
measure: Terminal Phase Elimination Half-life (T1/2) for MT203
timeFrame: Day 29 (Pre-dose and 2 and 6 hours post-dose)
measure: Ctrough: Maximum Observed Plasma Concentration Pre-Dose
timeFrame: Days 1, 15 and 29 Pre-dose
measure: Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma
timeFrame: Baseline and Days 2, 4, 6, 8 15, 29, 30, 35, 43, 56, 71, 99, End of trial (EOT) Up to Day 118
measure: Change From Baseline in MT203/GM-CSF Complexes in Plasma
timeFrame: Baseline and Days 2, 4, 6, 8 15, 29, 30, 35, 43, 56, 71, 99, EOT Up to Day 118
measure: Number of Participants With Anti-MT203 Antibodies
timeFrame: From Day 1 Up to Day 118
measure: Percentage of Participants With American College of Rheumatology (ACR 20) Response
timeFrame: Baseline and Days 13,27,43,56,71,99 and EOT Up to Day 118
measure: Change From Baseline in the Disease Activity Score 44-Erythrocyte Sedimentation Rate (DAS44-ESR)
timeFrame: Baseline and Days 13,27,43,56,71,99 and EOT Up to Day 118
Other outcomes:
Locations:
city: Sofia
country: Bulgaria
facility: Nycomed Investigational Site
city: Leids
country: Netherlands
facility: Nycomed Investigational Site
Study officials:
References:
citation: Huizinga TW, Batalov A, Stoilov R, Lloyd E, Wagner T, Saurigny D, Souberbielle B, Esfandiari E. Phase 1b randomized, double-blind study of namilumab, an anti-granulocyte macrophage colony-stimulating factor monoclonal antibody, in mild-to-moderate rheumatoid arthritis. Arthritis Res Ther. 2017 Mar 9;19(1):53. doi: 10.1186/s13075-017-1267-3.