A Trial to Evaluate the Safety and Tolerability of Namilumab (MT203) in Patients With Mild to Moderate Rheumatoid Arthritis

NCT01317797 | Completed Phase 1 Results

• 4 other identifiers: M1-1188-002-EM2010-018502-36U1111-1137-3923NL33507.058.10
• Study Type: interventional
• Target: 24
• Locations: 2 countries
• Sites: 2

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.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis; MT203; Human IgG1 monoclonal antibody; GM-CSF monoclonal antibody

Outcome Measures

Primary Outcomes (6)

• Number of Participants With Clinically Significant Clinical Laboratory Results

  Blood was collected for Haematology, Chemistry and Coagulation. Urine was collected for Urinalysis. Alert values for laboratory results include the following: Aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), gamma-glutamyl-transpeptidase (GGT), alkaline phosphatase (AP), total bilirubin (TBil): \> 3 times upper limit of normal (ULN). Creatinine and Glucose: \> 2 times ULN. Potassium \> 6.0 or \< 3.0 mmol/L. Haemoglobin: Male \< 8.0 ;Female \< 7.0 g/dL. Erythrocytes :Male \< 3.5 x 10\^12/L or \> 7 x 10\^12/L;Female \< 3.0 x 10\^12/L or \> 6.5 x 10\^12/L. White Blood Cells (WBC): \< 2.8 x10\^9/L or \> 16.0 x 10\^9/L. Eosinophils \> 20 % of cells in the WBC differential. Platelet Count \< 75 x 10\^9/L or 600 x 10\^9/L. No alert values were identified for Coagulation or Urinalysis.

  From Day 1 Up to Day 118

• Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings

  Alert values for ECG were: Heart rate \< 35 bpm or \> 120 bpm, QTc acc. to Bazett (absolute value)\> 500 ms or QTc acc. to Bazett (increase versus Baseline (pre-treatment).

  From Day 1 Up to Day 118

• Number of Participants With Clinically Significant Vital Signs

  Vital signs included Systolic Blood Pressure (BP), Diastolic BP, body temperature, heart rate. Alert values were: BP systolic \> 170 mmHg or \< 85 mmHg, BP diastolic \> 105 mmHg, Difference BP systolic vs. Baseline (pre-treatment) \> 40 mmHg or Pulse rate \< 35 bpm or \> 120 beats per minute (bpm).

  From Day 1 Up to Day 118

• Number of Participants With Clinically Significant Pulmonary Function Tests

  Pulmonary function was determined by forced expiratory volume in the first second (FEV1), forced vital capacity (FVC) and peak flow.

  From Day 1 Up to Day 118

• Number of Participants With Clinically Significant Physical Examination Findings

  The physical examination included body system assessments: eyes, head and neck (including thyroid), ears, nose and throat, lymph nodes, cardiovascular, lungs, mammae, abdomen (liver, spleen), genitals, limbs, central and peripheral nervous system, musculoskeletal system, skin \& nails, mucosae. The Investigator classified abnormal findings as either clinically significant or not clinically significant.

  From Day 1 Up to Day 118

• Number of Participants Reporting One or More Treatment Emergent Adverse Events

  An Adverse Event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.

  From Day 1 Up to Day 118

Secondary Outcomes (12)

• Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MT203

  Day 1 and 29 (Pre-dose and 2 and 6 hours post-dose)

• Cmax: Maximum Observed Plasma Concentration for MT203

  Day 1 and 29 (Pre-dose and 2 and 6 hours post-dose)

• AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for MT203

  Day 1 and 29 (Pre-dose and 2 and 6 hours post-dose)

• AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for MT203

  Day 29 (Pre-dose and 2 and 6 hours post-dose)

• AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for MT203

  Day 29 (Pre-dose and 2 and 6 hours post-dose)

Study Arms (3)

Namilumab 150 mg

EXPERIMENTAL

Namilumab (MT203) 150 mg (low dose), subcutaneous (SC) injection, on Days 1, 15 and 29.

Drug: namilumab (MT203)

Namilumab 300 mg

EXPERIMENTAL

Namilumab (MT203) 300 mg (high dose), SC injection, on Days 1, 15 and 29.

Drug: namilumab (MT203)

Placebo

PLACEBO COMPARATOR

Namilumab-matching placebo, SC injection, on Days 1, 15 and 29.

Drug: Placebo

Interventions

namilumab (MT203) DRUG

administered three times, subcutaneous in the abdomen

Namilumab 150 mg; Namilumab 300 mg

Placebo DRUG

administered three times, subcutaneous in the abdomen

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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
• Age ≥ 18 years at Screening
• Body weight at least 50 kg at Screening; BMI: ≥ 18.0 and ≤ 30.0 kg/m2 at Screening
• Negative tuberculosis test at Screening
• 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.

You may not qualify if:

• Participation in another clinical trial or previous dosing in this trial
• Use of specified medications within certain timeframes or use of certain comedications
• History or presence of specified diseases
• Drug abuse
• Certain laboratory parameters outside a specified range
• Donation of blood
• Relevant decrease in lung function
• Infections, frequent or chronic infections, herpes zoster
• Females: positive pregnancy test
• Presence of history of tuberculosis
• History of malignancy

Sponsors & Collaborators

• Takeda: lead

Study Sites (2)

Nycomed Investigational Site

Sofia, Bulgaria

Location

Nycomed Investigational Site

Leids, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 28274253 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

namilumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Medical Director, Clinical Science
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2011
• First Posted: March 17, 2011
• Study Start: March 1, 2011
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: August 20, 2015
• Results First Posted: August 20, 2015

Record last verified: 2015-07

Locations

BU (1); NL (1)