Rheumatoid Arthritis
Conditions
Interventions
Product Name: bIAP
Product Code: EC 3.1.3.1
Pharmaceutical Form: Solution for injection
INN or Proposed INN: bovine intesastinal alkaline phosphatase (bIAP)
CAS Number: EC 3.1.3.1
Current Sponsor code
Sponsors
Alloksys Life Sciences B.V.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The total cohort of patients is small, only 10 patients. We will attempt to make the population as homogenous as possible. 1.12 Inclusion Criteria 1. Male or non-pregnant, non-lactating female patients of any race with an age >18 years. Woman of child-bearing potential must be on regular contraceptives throughout the trial. Pregnancy tests will be used at screening for women of child bearing years. 1A: RA according to the 1987 revised ARA criteria (Arnett 1987) with an active disease with DAS28>3.2 despite the prior or concurrent use of DMARDs. 2. Patients may be on no active therapy or may be on continuous DMARD therapy including Methotrexate, Sulphasalazine, Leflunomide, Hydroxychloroquine, Myocrisin alone or in combination, or on NSAID treatment, or on steroid (prednisolone not more than 10mg/day) provided that the regime has been stable for 30 days prior to screening. All prior medication should be maintained at steady dosing throughout the 8th day laboratory phase. Intra-articular or subcutaneous steroid are not allowed during the laboratory phase. Alterations may be made at the discretion of the investigator during the 3-month clinical follow-up period in accordance with standard of care. All such alterations will be recorded and reported. Joints receiving IA injections will be counted as positive for subsequent tender and swollen joint counts. 3. Patients must have a measurable acute phase response: CRP (> 10mg/dl)or ESR > 25. (to be measured on routine lab range CRP/ ESR/AP/ standard biochemistry) 4. Patients eligible for treatment with biological TNFa blockers and who are awaiting the administration of such treatment may enrol in the laboratory and safety protocols Data for Clinical Phase observations will be collected but will be handled as last observation carried forward for the final records prior to the administration of TNF blocking agent, should that occur within the 3-month Clinical Phase. The administration of TNFa blockers will not be delayed for the protocol. 5. Patients who have given written informed consent prior to participation in the trial and who undertake to comply with the protocol. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Exclusion Criteria 1. Patients who are unwilling or unable to be fully evaluated for follow-up. 2. Patients who have an active infection or who are suspected of having systemic infection and or patients that are treated with antibiotics. 3. Patients who have evidence of significant hepatic disease, including history of clinical signs or laboratory values of total bilirubin > 34.2 umol/L (> 2.0 mg/dL), ALT (>120) or AST (>135) corresponding to > 3X upper limit of normal. 4. Alkaline phosphatase levels must be less 145 IU/L (routine clinical method)and patients with too low observed acute phase rsponse (ESR/CRP) on screening bloods. 5. Patients who received investigational drugs in the 30 days prior to study drug administration, or are currently participating in a study during which the administration of investigational drugs within one month is anticipated. 6. Patients who have renal insufficiency (history of creatinine >177umol/L or >2.0 mg/dL) or chronic renal failure requiring dialysis. 7. Patients with severe neurological deficits (see Appendix I). 8. Patients who have a recent history of drug substance or alcohol abuse. 9. Patients with a diagnosis of idiopathic thrombocytopenia. 10. Patients with a history of cancer who have received chemotherapy or radiation therapy within the past 3 months. Patients receiving only adjuvant hormonal therapy are not excluded. If the cancer has not resolved completely, the patient should not be enrolled without permission of Alloksys. 11. Patients receiving oral glucocorticoids >10mg /day or any IV, IM or Intra articular dosing within 30 days of commencing the protocol. 12. Patients who are vegetarians or veganists or those patients that may be expected not to be tolerant to bovine proteins. 13. Patients who are, in the opinion of the Investigator or the Sponsor, unsuitable for the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Primary Outcome Measures. Days 1-8. The Laboratory phase. This study is designed to test the following hypotheses: SC administration of 2 injections of 2000 IU bIAP daily (8 hours apart) for 3 days results in a measurable reduction of TNFa and IL-6 in blood, measured by Luminex cytokine profiling along with conventional measures of ESR and CRP. These are the primary outcome measures. Sub Primary and Exploratory Laboratory Measures Cytokines Additionally, a number of potential cytokine targets will be measured in the same samples in an exploratory fashion including IL-1a, IL1b,IL-8, IL-10, IL-12, IL-15, IL-17, IL-18, sTNFr and RANKL. Alkaline Phosphatase In previous CABG studies (APPIRED 1 and APPIRED pilot 2) a late peak of endogenous AP production was seen 3-4 hours after after IV administration of exogenous AP. This endogenous AP response lasted for more than 36 hours. This has also been seen after SC admin in experiemntal piglets (see IB). Therefore, the response of endogenous AP levels to exogenous SC administration will also be explored. Co-Primary Safety Outcomes and Safety Design Since SC administration of bIAP is novel in humans, we will specifically record cutaneous reactions as a co-primary safety variable. Patients will be observed throughout day 1 of injection then at times of injection on days 2 and 3, then once daily on days 4, 6 and 8. Full safety monitoring and AE recording will be carried out. As an additional safety feature, patients will be treated in cohorts. The first patient will complete the laboratory phase and nreports made to the DMC before the second cohort of two patients are treated, these will complete the laboratory phase before further cohorts of three then a final four patients are treated..;Main Objective: The REUMAP study is a safety-biased, open-label proof of concept study that aims to explore a possible beneficial effect of alkaline phosphatase in active RA patients who show insufficient response t | — |
Countries
United Kingdom
Outcome results
None listed