Cx611-0101, eASCs Intravenous Administration to Refractory Rheumatoid Arthritis Patients

NCT01663116 | Completed Phase 1 DMC

• 1 other identifier: Cx611-0101
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 23

Brief Summary

Phase Ib/IIa clinical trial of a new medicinal product of the somatic cell therapy class (eASCs). This study is designed as a multicenter, single blind, fixed dose escalation, with three treatment groups, controlled with placebo (randomization 3:1) whose target population are patients with rheumatoid arthritis refractory to at least two biologic.

Conditions

Rheumatoid Arthritis Aggravated

Keywords

Rheumatoid arthritis; Expanded adipose derived allogeneic adult stem cells (eASCs)

Outcome Measures

Primary Outcomes (1)

• Number of Adverse Events and Severe Adverse Events

  Total number of Adverse Events and Severe Adverse Events, related and non-related with the medication will be recorded as a measure of tolerability and safety.

  6 months follow up after the first administration

Secondary Outcomes (1)

• Proportion of ACR20 patients/ACR50 patients/ACR70 patients (swollen joints*, tender joints**, physician global assessment***, patient global assessment***, patient´s assessment of pain ***, ESR/CRP, HAQ score)

  At selection and screening visit, and once per month during 6 months after the last administration

Study Arms (2)

Treatment

EXPERIMENTAL

1. first cohort: 1 million stem cells/kg administered at days 1, 8 and 15 2. second cohort: 2 million stem cells / kg administered at days 1, 8 and 15 3. third cohort: 4 million stem cells / kg administered at days 1, 8 and 15

Genetic: Stem cells

Placebo

PLACEBO COMPARATOR

Lactate Ringer´s solution

Genetic: Placebo

Interventions

Stem cells GENETIC

1. first cohort: 1 million stem cells/kg administered at days 1, 8 and 15 2. second cohort: 2 million stem cells / kg administered at days 1, 8 and 15 3. third cohort: 4 million stem cells / kg administered at days 1, 8 and 15

Treatment

Placebo GENETIC

1. first cohort: 20 ml administered at days 1, 8 and 15 2. second cohort: 40 ml administered at days 1, 8 and 15 3. third cohort: 80 ml administered at days 1, 8 and 15

Placebo

Eligibility Criteria

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

You may qualify if:

• Must understand and voluntarily sign an informed consent form prior to the conduct of any study related assessment/procedures.
• Subjects with RA under treatment with at least one non-biologic-DMARD and failure to treatment with at least two biologics.
• Of either gender, aged ≥ 18 years at time of consent.
• Able to adhere to the study visit schedule and other protocol requirements.
• Have a diagnosis of RA for ≥6 months.
• EULAR DAS28-ESR activity criteria \>3.2.
• Four tender joints to palpation and four swollen joints, based on a 68/66-joint count.
• Be receiving treatment on an outpatient basis.
• If taking methotrexate, leflunomide, or sulfasalazine, must have been treated for at least 16 weeks and on a stable dose (oral methotrexate ≤ 25 mg/week; parenteral methotrexate ≤ 20 mg/week; leflunomide ≤ 20 mg/day; sulfasalazine ≤ 3 g/day) for at least 4 weeks prior to the start of treatment and throughout the study. (See also section 7.5). The rest of the DMARDs (gold salts, etc) should be maintained at stable doses during at least the 4 weeks prior to the start of treatment and throughout the study (see also section 7.5).
• If taking oral corticosteroids, must be on a stable dose of prednisone ≤ 10 mg/day or equivalent for at least 1 month prior to screening. ( See also section 7.5).
• If taking NSAIDs, must be on stable dose for at least 2 weeks prior to screening and until they have completed the Week 24 study visit. (See also section 7.5).
• Male subjects (including those who have had a vasectomy) must agree to use barrier contraception (latex condoms) when engaging in activity in which conception is possible while on study medication and for at least 28 days after taking the last dose of study medication.
• Females of Childbearing Potential\* must have a negative urine pregnancy test at Screening and Baseline and must be willing to use one medically approved form of birth control when engaging in activity in which conception is possible while on study medication and for at least 28 days after taking the last dose of study medication.
• A female of childbearing potential is a sexually mature female who 1) has not undergone a hysterectomy (the surgical removal of the uterus) or bilateral ovariectomy (the surgical removal of both ovaries) or 2) has not been postmenopausal for at least 24 consecutive months (i.e., has had menses at any time during the preceding 24 consecutive months).

You may not qualify if:

• A patient CANNOT be recruited into this study if any of the following criteria is met:
• Treatment with biologics within the following period prior to the start of treatment:
• Infliximab: 8 weeks
• Etanercept: 2 weeks
• Adalimumab and certolizumab: 4 weeks
• Abatacept, tocilizumab and golimumab: 8 weeks
• Rituximab: 6 months
• Anakinra: 3 days No treatment with biologics is allowed during the first 12 weeks after the start of the study treatment. Thus, the patients should have complied with the periods indicated above, and should not receive any biologics during the period specified.
• Presence of a severe bleeding or thrombotic disorder.
• History of known pulmonary embolism or known secondary anti-phospholipid syndrome.
• Received any of the following treatments within 2 years prior to study entry: anti-cancer therapy (e.g. alkylating agents, anti-metabolites, purine analogues, monoclonal antibodies for malignancy).
• Received within 4 weeks prior to the start of treatment: intra-articular, intramuscular or intravenous corticosteroids. (See also section 7.5).
• Past or current malignant melanoma.
• Past or current malignancy; except for in situ cervical cancer, non-invasive basal cell and squamous cell skin carcinoma, superficial bladder tumors (Ta and Tis) with a complete response duration of \>10 years. In the case of lymphoma or breast cancer patients will be allowed to participate in the trial with a complete response duration of \>20 years.
• Other autoimmune diseases, previous or current inflammatory joint disease other than rheumatoid arthritis, currently active or previous recurrent bacterial, viral, fungal, or other infections including, but not limited to, tuberculosis and atypical mycobacterial disease, clinically significant abnormalities on chest radiograph, hepatitis B and C, and recurrent herpes zoster.

Sponsors & Collaborators

• Tigenix S.A.U.: lead

Study Sites (23)

Hospital General de Mérida

Mérida, Badajoz, 06800, Spain

Location

Hospital U. Central de Asturias

Oviedo, Principality of Asturias, 33006, Spain

Location

Hospital U. de Canarias

San Cristóbal de La Laguna, Tenerife, 38320, Spain

Location

Hospital de Cruces

Barakaldo, Vizcaya, 48903, Spain

Location

Hospital de Basurto

Bilbao, Vizcaya, 48013, Spain

Location

Complejo Hospitalario U. A Coruña

A Coruña, 15006, Spain

Location

Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic i Provincial

Barcelona, 08036, Spain

Location

Hospital Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Hospital Reina Sofía

Córdoba, 14004, Spain

Location

Hospital Clínico San Cecilio

Granada, 18012, Spain

Location

Hospital U. Virgen de las Nieves

Granada, 18014, Spain

Location

Hospital U. de Guadalajara

Guadalajara, 19002, Spain

Location

Hospital de La Princesa

Madrid, 28006, Spain

Location

Hospital U. Gregorio Marañon

Madrid, 28007, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital U. La Paz

Madrid, 28046, Spain

Location

Hospital Carlos Haya

Málaga, 29010, Spain

Location

Hospital U. Marques de Valdecilla

Santander, 39008, Spain

Location

Hospital Ntra. Sª de Valme

Seville, 41014, Spain

Location

Hospital Virgen Macarena

Seville, 41071, Spain

Location

Hospital La Fe

Valencia, 46009, Spain

Location

Hospital Dr. Peset

Valencia, 46017, Spain

Location

Related Publications (1)

• Alvaro-Gracia JM, Jover JA, Garcia-Vicuna R, Carreno L, Alonso A, Marsal S, Blanco F, Martinez-Taboada VM, Taylor P, Martin-Martin C, DelaRosa O, Tagarro I, Diaz-Gonzalez F. Intravenous administration of expanded allogeneic adipose-derived mesenchymal stem cells in refractory rheumatoid arthritis (Cx611): results of a multicentre, dose escalation, randomised, single-blind, placebo-controlled phase Ib/IIa clinical trial. Ann Rheum Dis. 2017 Jan;76(1):196-202. doi: 10.1136/annrheumdis-2015-208918. Epub 2016 Jun 7.

  PMID: 27269294 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

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

Study Officials

• José María Alvaro-Gracia, MD, PhD

  Fundación de Investigación Biomédica - Hospital Universitario de La Princesa

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2011
• First Posted: August 13, 2012
• Study Start: March 1, 2011
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: April 12, 2019

Record last verified: 2019-04

Locations

ES (23)