Clinical trial NCT01261403: Study of Human Placenta-derived Cells (PDA001) to Evaluate the Safety and Effectiveness for Patients With Active Rheumatoid Arthritis
Official title: A Phase 2, Randomized, Double- Blind, Placebo-controlled, Multi-center Study to Evaluate the Safety and Efficacy of Intravenous Infusion of Human Placenta-Derived Cells (PDA001) for the Treatment of Adults With Active Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Human Placenta-Derived Cells
Lead sponsor: Celularity Incorporated
Sponsor class: INDUSTRY
Collaborators: name: Celgene Corporation
First posted: 2010-12-16
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of the study is to assess the safety and efficacy of 2 dose groups (PDA001 versus vehicle control) in subjects with active rheumatoid Arthritis. The secondary objectives of the study are to determine the clinical response at defined visit intervals, determine the time to flare of RA symptoms and to quantify changes in inflammatory markers including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum amyloid A (SAA), and IL-6.


Eligibility criteria: Inclusion Criteria:

Subjects must satisfy the following criteria to be enrolled in the study:

1. Diagnosis of RA as defined by the 1987-revised ACR criteria.
2. RA, characterized by at least 6 out of 66 swollen joints and 6 out of 68 tender joints at Screening and Baseline, and at least 2 of the following: a C reactive protein level (CRP), greater than the upper limit of normal (ULN) ³ 1 mg/dl, an erythrocyte sedimentation rate (ESR) of at least 28 mm per hour, or morning stiffness lasting longer than 45 minutes.
3. Non responsive or intolerant to a minimum of 2 RA therapies which are classified as DMARDs, biologics, or corticosteroids.
4. Biological medication must be discontinued 30 day prior to the first dose of study drug, except golimumab and actemra which are 60 days, and infliximab, alefacept and efalizumab, which must have been discontinued 90 days prior to the first dose of IP.
5. Cytotoxic agents, including but not limited to chlorambucil, cyclophosphamide, nitrogen mustard, or other alkylating agents must have been discontinued 90 days prior to the first dose of IP.
6. Subjects must be able to tolerate intravenous infusions in both arms.
7. There should be no change in RA medication dose anticipated during the initial treatment and re treatment periods and the respective 12 week follow-up period for each dosing treatment period. The following rules apply for anti-rheumatic medications taken during the study:
8. DMARDs must have must have been stable for least 90 days prior to dosing with IP.
9. Low -dose corticosteroids are permitted (prednisolone ≤ 10 mg per day or equivalent). Corticosteroids must have been stable for at least 30 days prior to dosing with IP.
10. DMARDs and corticosteroids must remain stable throughout the initial 3 months of study and throughout subsequent treatment periods

The presence of any of the following will exclude a subject from enrollment:

1. Prior use of rituximab and other B-cell depleting therapies, abatacept, prior use of more than 2 biologic therapies.
2. Subject has received an investigational agent in any indication-within 60 days (or 5 half-lives, whichever is longer) prior to treatment with IP.
3. Subject has received previous cell therapy.
4. Serum creatinine concentration \> 2.0 mg/dl at screening.
5. Alkaline phosphatase \> 2.5x the upper limit of normal at screening.
6. Bilirubin level \> 1.5 mg/dL (unless subject has known Gilbert's disease).
7. Untreated chronic infection or treatment of any infection with antibiotics within 4 weeks prior to dosing with IP.
8. Positive HIV test at Screening. Positive Hepatitis B surface antigen at Screening. Positive Hepatitis C antibody at Screening.
9. Organic heart disease (e.g., congestive heart failure), myocardial infarction within six (6) months prior to screening or clinically significant findings on ECG at screening. Clinically significant arrhythmia.
10. Primary or secondary immunodeficiency.

Primary outcomes:
measure: Number/Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response within 12 weeks following the initial dose of study drug
timeFrame: Baseline through Week 12
Secondary outcomes:
measure: Number/Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at 6 months
timeFrame: Baseline and 6 months
measure: Number/percent of subjects achieving an ACR 20 clinical response at each scheduled visit during the first 12 months following the first infusion of study drug.
timeFrame: Baseline and each scheduled visit through 12 months following the first infusion of study drug
measure: Number/percent of subjects achieving an ACR 50 clinical response at each scheduled visit during the first 12 months following the first infusion of study drug.
timeFrame: Baseline and each scheduled visit through 12 months following the first infusion of study drug.
measure: Number/percent of subjects achieving an ACR 70 clinical response at each scheduled visit during the first 12 months following the first infusion of study drug.
timeFrame: Baseline and each scheduled visit through 12 months following the first infusion of study drug.
measure: Number/percent of subjects achieving a clinical response based on their Clinical Disease Activity Index (CDAI) at each scheduled visit during the first 12 months following the first infusion of study drug.
timeFrame: Baseline and each scheduled visit through 12 months following the first infusion of study drug
measure: Number/percent of subjects achieving a clinical response based on their Disease Activity Score (DAS 28) score at each scheduled visit during the first 12 months following the first infusion of study drug
timeFrame: Baseline and each scheduled visit through 12 months following the first infusion of study drug
measure: Number/Percent of Participants Who Achieve the European League Against Rheumatism (EULAR) Response Criteria Using CRP at Month 12
timeFrame: Baseline and each scheduled visit through 12 months following the first infusion of study drug.
measure: The change from baseline in the ACR core components. ACR Core Component #1: Percentage Change From Baseline in the Swollen Joint Count at each scheduled visit.
timeFrame: Baseline and each scheduled visit through 12 months following the first infusion of study drug
measure: ACR Core Component #2: Percentage Change From Baseline in the Swollen Joint Count at each scheduled visit through Month 12 following the initial infusion of study drug
timeFrame: Baseline and at each scheduled visit through Month 12 following the initial infusion of study drug
measure: ACR Core Component #3 Percentage Change From Baseline in the Subject Assessment of Pain at each scheduled visit through Month 12 following the initial dose of study drug
timeFrame: Baseline and at each scheduled visit through Month 12 following the initial dose of study drug
measure: ACR component #4 Percentage Change From Baseline in the Subject Global Assessment of Disease Activity at each scheduled visit through Month 12 following the initial dose of study drug
timeFrame: Baseline and at each scheduled visit through Month 12 following the initial dose of study drug
measure: ACR Component #5 Percentage Change From Baseline in the Physician Global Assessment of Disease Activity at each scheduled visit through Month 12 following the initial dose of study drug
timeFrame: Baseline and Month 12
measure: ACR Component #6; Percentage Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at each scheduled visit through Month 12 following the initial dose of study drug
timeFrame: Baseline and at each scheduled visit through Month 12 following the initial dose of study drug
measure: ACR Component#7 Percentage Change From Baseline in the High Sensitivity C-Reactive Protein (CRP) at each scheduled visit through Month 12 following the initial dose of study drug
timeFrame: Baseline at each scheduled visit through Month 12 following the initial dose of study drug
measure: ACR Component #8 Percentage Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at each scheduled visit through Month 12 following the initial dose of study drug
timeFrame: Baseline and at each scheduled visit through Month 12 following the initial dose of study drug
measure: Change from baseline in rheumatoid factors at each scheduled visit through Month 12 following the initial dose of study drug
timeFrame: Baseline and each scheduled visit through Month 12 following the initial dose of study drug
measure: Time to flare of Rheumatoid Arthritis (RA) symptoms
timeFrame: At defined intervals
measure: Changes in inflammatory markers including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum amyloid A (SAA), and IL-6
timeFrame: At defined intervals
measure: Change From Baseline in the Disease Activity Score 28 (DAS 28) Using CRP
timeFrame: Baseline and Month 6
measure: Change From Baseline in the Clinical Disease Activity Index (CDAI) at Month 3
timeFrame: Baseline and Month 3
measure: Change From Baseline in the Clinical Disease Activity Index (CDAI) at Month 6
timeFrame: Baseline and Month 6
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Pinnacle Research Group
state: Alabama
city: Arcadia
country: United States
facility: Advanced Pain Research Institute
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Palm Desert
country: United States
facility: Desert Medical Advances
state: California
city: Coral Gables
country: United States
facility: Sanitas Research
state: Florida
city: Orlando
country: United States
facility: Compass Research, LLC
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: Paducah
country: United States
facility: Four Rivers Clinical Research Inc.
state: Kentucky
city: Monroe
country: United States
facility: Arthritis and Diabetes Clinic, Inc
state: Louisiana
city: Eagan
country: United States
facility: St. Paul Rheumatology, PA
state: Minnesota
city: Lakewood
country: United States
facility: SNS Rheumatology
state: New Jersey
city: Mayfield
country: United States
facility: David R. Mandel, MD, Inc.
state: Ohio
city: Oklahoma City
country: United States
facility: Health Research of Oklahoma
state: Oklahoma
city: Oklahoma City
country: United States
facility: Health Research Institute
state: Oklahoma
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
city: Dallas
country: United States
facility: Metroplex Clinical Research Center
state: Texas
Study officials:
affiliation: Celularity Incorporated
name: Solveig Ericson, MD
role: STUDY_DIRECTOR
References: