- ICH GCP
- Registr klinických studií v USA
- Klinická studie NCT01123655
Phase 1 Trial of Type II Collagen (CII) APL A12 in Rheumatoid Arthritis Patients
Phase 1 Trial of CII APL A12 in Rheumatoid Arthritis Patients
Přehled studie
Detailní popis
The study will have 3 treatment arms each with 10 patients who have demonstrated T cell immunity to CII and have an in vitro response to APL A12 at the screening visit. Patients will be randomized to one of the 3 treatment arms. Each of the 3 treatments will be given for 16 weeks.
In keeping with a sequential dose escalation strategy, the originally proposed randomization scheme will be modified so that subjects will be randomized to receive either the lowest dose (30 mg) or placebo (Block 1), followed by the next dose (50 mg) or placebo (Block 2). We will begin with the lowest dose (30 g/day) and enroll 6 to receive 30 g/day APL A12 and 2 to receive placebo for 16 weeks. Results will be reported to the Data Monitoring Committee (DMC) for a decision to proceed to the next block based on indications of safety. If this dose does not cause adverse events or toxicity or worsens RA, we will proceed to enroll patients to receive 30 ug, or 50 g/day APL A12 or placebo for 16 weeks. A total of 32 subjects will be randomized to obtain 24 subjects who complete the study. Recruitment was difficult. Only 22 patients were randomized. There were not enough 50mcg patients enrolled so 2 treatment groups was analyzed. Arm 1 included 30 and 50 mcg and Arm 2 represents the patients that received placebo.
Typ studie
Zápis (Aktuální)
Fáze
- Fáze 1
Kontakty a umístění
Studijní místa
-
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Tennessee
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Memphis, Tennessee, Spojené státy, 38104
- Memphis VA Medical Center, Memphis, TN
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria:
Patients must meet the following criteria for participation in the study.
- Male or female; age > 18 years.
- American College of Rheumatology (ACR) 1988 revised criteria for rheumatoid arthritis.
- Onset of disease age 16 or older.
- Onset of disease at least 3 months prior to enrollment.
- RA patients ages 18-85 with RA of 3 month duration which in the opinion of the examining rheumatologist is "clinically stable" and will likely not require adjustment of doses of Disease-modifying antirheumatic drugs (DMARDS), NSAIDS, prednisone, anti-tumor necrosis factor (anti-TNF) alpha therapies for the 16 weeks of the treatment phase of the study.
- Patients must agree to discontinue all "herbal remedies" as described in this protocol.
- Women of childbearing age will be advised to use effective means of contraception for the treatment phase of the trial and for 90 days thereafter. They must have a negative urine pregnancy test at the randomization visit. (Required by the FDA.)
- Men will be advised to use effective means of contraception for the treatment phase of the trial and for 90 days thereafter. (Required by the FDA.)
- Crohn's Disease Activity Index (CDAI) less than or equal to 30 at the baseline visit.
- Patients with a past history of malignant neoplasm will be eligible if they are 1 or greater years with no recurrence of malignant neoplasm.
Exclusion Criteria:
- Inability to render an informed consent in accordance with institutional guidelines.
- Participation in another clinical research study involving the evaluation of another investigational drug within 90 days of entry into this study.
- RA patients on >7.5 mg prednisone a day.
- RA patients with intra-articular corticosteroid injections during the previous 30 days.
- Concurrent serious medical condition which in the opinion of the investigator makes the patient inappropriate for the study. Hepatitis B abd/or C patients with inactive disease (as determined by PI) will be enrolled.
- Positive urine pregnancy test
- Age 85 years or greater.
- Use of "fish oil" within the previous 4 weeks of the baseline visit.
- Therapy consisting of auranofin or cyclophosphamide (all other DMARDs are allowed).
- Previous autologous or heterologous stem cell transplantation.
- Active malignant neoplasm or past treatment for malignant neoplasm 1 year from screening visit.
- Use of oral CII within the past 1 year. (Since oral tolerance is short-lived, we will permit patients in the study who have been off oral CII for > 1 year)
- Diabetes requiring insulin or on oral medications must be well managed at baseline. Adjustment of insulin or on oral medications will be allowed during the study.
- Serum creatinine 2.0 mcg/dL.
- An 1(II) IFN value <100% of the PBS IFN value within 1 month or less prior to the baseline and less than 25% reduction in APL A12 + 1(II) IFN from 1(II) IFN concentration.
- CDAI > 30 at the baseline visit.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Čtyřnásobek
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
---|---|
Experimentální: Arm 1
The study will have 3 treatment arms each with 10-12 patients who have demonstrated T cell immunity to CII and have an in vitro response to APL A12 at the screening visit. Patients will be randomized to one of the 2 treatment arms (30 micrograms APL A12 or placebo). Each of the 2 treatments will be given for 16 weeks. Intervention: Drug treatment will be stopped or interrupted if indicated and medical care will be given as appropriate. Intervention: Drug treatment will be stopped or interrupted if indicated and medical care will be given as appropriate. |
Intervention: Drug treatment will be stopped or interrupted if indicated.
Medical care will be provided at no cost to the patient.
Drug treatment will be stopped or interrupted if indicated.
Medical care will be provided at no cost to the patient.
|
Experimentální: Arm 2
The next group will receive a higher dose (50 micrograms) and/or placebo (Block 2). Intervention: Drug treatment will be stopped or interrupted if indicated and medical care will be given as appropriate. |
Intervention: Drug treatment will be stopped or interrupted if indicated.
Medical care will be provided at no cost to the patient.
Drug treatment will be stopped or interrupted if indicated.
Medical care will be provided at no cost to the patient.
|
Experimentální: Arm 3
Block 3 (Arm 3) will include placebo and both doses of APL/A12 to ensure 10-12 patients are enrolled in each arm ( total of approximately 32 subjects) so we will have 24 subjects who complete the 16 weeks of study treatment. Arms 2 and 3 will run simultaneously. Intervention: Drug treatment will be stopped or interrupted if indicated. |
Intervention: Drug treatment will be stopped or interrupted if indicated.
Medical care will be provided at no cost to the patient.
Drug treatment will be stopped or interrupted if indicated.
Medical care will be provided at no cost to the patient.
|
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
---|---|---|
Number and Percent of Participants With Reduction of Immunity to Collagen Type-II After APLA-12 Treatment.
Časové okno: 16 weeks
|
The primary outcome variable is the presence of a > 25% reduction in net IFN concentration in supernatants of 1(II)-stimulated PBMC cultures from baseline after 16 weeks of treatment.
|
16 weeks
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
---|---|---|
Flow Cytometry
Časové okno: baseline and 8 or 16 weeks
|
Change in Percentage of CD4+CD25+FoxP3 T regulatory cells, CD4+IL-10+ cells, CD4+ IL-4+ cells, CD4+IL17+ cells.
Some patients had only had enough blood collected at 8 weeks or 16 weeks or dropped out after 8 weeks, and we used/combined what was available.
|
baseline and 8 or 16 weeks
|
Clinical Disease Activity Index (CDAI) at 0 and 16 Weeks Follow up
Časové okno: 0 and16 weeks
|
Interpretation of Clinical Disease Activity Index (CDAI) scores < 2.8 indicate remission; >2.8 and <= 10 indicates low disease activity; >10 and <= 22 indicates moderate disease activity; >22 indicates high disease activity.
|
0 and16 weeks
|
Change in Cytokine Profile From Baseline and 16 Weeks
Časové okno: 0 and 16 weeks
|
Cytokines assessed are IL-10, IL-13, IL-5, IL-1B, IL-9, IL-17A, IL-6, IL-21, TGF-B, TNFa,and MIP3A.
|
0 and 16 weeks
|
Change in IgG and IgA Immunoglobulin From Baseline to 8 or 16 Weeks
Časové okno: baseline and 8 or 16 wks
|
The change was computed between baseline and 8 or 16 weeks, whichever was available.
|
baseline and 8 or 16 wks
|
Neutrophils Counts at 0 and 16 Weeks
Časové okno: Baseline and 16 weeks
|
Laboratory Results of A12 vs Placebo:Complete blood count Neutrophil count to determine whether APL has any effect on routine blood counts, chemistries, electrolytes, immunoglobulin to measure potential toxicities
|
Baseline and 16 weeks
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A12 Treated vs Placebo of Monocytes.
Časové okno: Baseline and 16 wks
|
Laboratory Results of A12 treated vs Placebo of Monocytes to determine whether APL has any effect on routine blood counts, chemistries, electrolytes, immunoglobulin to measure potential toxicities
|
Baseline and 16 wks
|
Eosinophils
Časové okno: Baseline and 16 weeks
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Laboratory Results of A12 treated vs Placebo of Eosinophils to determine whether APL has any effect on routine blood counts, chemistries, electrolytes, immunoglobulin to measure potential toxicities
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Baseline and 16 weeks
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Laboratory Results of A12 vs Placebo: Lymphocytes
Časové okno: 0-16 weeks
|
Measure to determine whether APL has any effect on routine blood counts, chemistries, electrolytes, immunoglobulin to measure potential toxicities
|
0-16 weeks
|
Laboratory Results of A12 vs Placebo: Basophils
Časové okno: Baseline and 16 weeks
|
Measure to determine whether APL has any effect on routine blood counts, chemistries, electrolytes, immunoglobulin to measure potential toxicities
|
Baseline and 16 weeks
|
Hematocrit
Časové okno: 0-16 weeks
|
Laboratory Results of A12 vs Placebo to determine whether APL has any effect on routine blood counts, chemistries, electrolytes, immunoglobulin to measure potential toxicities
|
0-16 weeks
|
Laboratory Results of A12 vs Placebo-Total Immunoglobulin (Immature Granulocytes)
Časové okno: Baseline and 16 weeks
|
Measure to determine whether APL has any effect on routine blood counts, chemistries, electrolytes, immunoglobulin to measure potential toxicities
|
Baseline and 16 weeks
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Red Blood Cell Distribution Width (RDW)
Časové okno: 0 and 16 weeks
|
Laboratory Results of A12 vs Placebo RDW is a measure of the range of variation of red blood cell volume reported as part of a standard blood count to determine whether APL has any effect on routine blood counts, chemistries, electrolytes, immunoglobulin to measure potential toxicities
|
0 and 16 weeks
|
Hemaglobin
Časové okno: Baseline and 16 weeks
|
Laboratory Results of A12 vs Placebo to determine whether APL has any effect on routine blood counts, chemistries, electrolytes, immunoglobulin to measure potential toxicities
|
Baseline and 16 weeks
|
Red Blood Cells
Časové okno: 0-16 weeks
|
Laboratory Results of A12 vs Placebo to determine whether APL has any effect on routine blood counts, chemistries, electrolytes, immunoglobulin to measure potential toxicities
|
0-16 weeks
|
White Blood Count
Časové okno: 0-16 weeks
|
Laboratory Results of A12 vs Placebo to determine whether APL has any effect on routine blood counts, chemistries, electrolytes, immunoglobulin to measure potential toxicities
|
0-16 weeks
|
Platelets
Časové okno: 0-16 weeks
|
Laboratory Results of A12 vs Placebo to determine whether APL has any effect on routine blood counts, chemistries, electrolytes, immunoglobulin to measure potential toxicities
|
0-16 weeks
|
AST, ALT and Alkaline Phosphatase
Časové okno: 0-16 weeks
|
Laboratory Results of A12 vs Placebo to determine whether APL has any effect on routine blood counts, chemistries, electrolytes, immunoglobulin to measure potential toxicities
|
0-16 weeks
|
Ca, BUN, Glucose,Creatinine, Total Bilirubin
Časové okno: 0-16 weeks
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Laboratory Results of A12 vs Placebo-CMP to determine whether APL has any effect on routine blood counts, chemistries, electrolytes, immunoglobulin to measure potential toxicities
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0-16 weeks
|
Sodium, Potassium and Chloride
Časové okno: 0-16 weeks
|
Laboratory results of A12 vs Placebo to determine whether APL has any effect on routine blood counts, chemistries, electrolytes, immunoglobulin to measure potential toxicities
|
0-16 weeks
|
Total Protein, Albumin
Časové okno: 0-16 weeks
|
Laboratory Results of A12 vs Placebo to determine whether APL has any effect on routine blood counts, chemistries, electrolytes, immunoglobulin to measure potential toxicities
|
0-16 weeks
|
C-reactive Protein
Časové okno: 0-16 weeks
|
Laboratory Results of A12 vs Placebo to determine whether APL has any effect on routine blood counts, chemistries, electrolytes, immunoglobulin to measure potential toxicities
|
0-16 weeks
|
Rheumatoid Factor
Časové okno: 0-16 weeks
|
Laboratory Results of A12 vs Placebo to determine whether APL has any effect on routine blood counts, chemistries, electrolytes, immunoglobulin to measure potential toxicities
|
0-16 weeks
|
Sedimentation Rate
Časové okno: 0-16 weeks
|
Laboratory results of A12 vs Placebo to determine whether APL has any effect on routine blood counts, chemistries, electrolytes, immunoglobulin to measure potential toxicities
|
0-16 weeks
|
Laboratory Results of A12 vs Placebo Anti-CCP Antibody
Časové okno: 0-16 weeks
|
0-16 weeks
|
|
Patient Global Assessment (PGA) and Physician Global Assessment
Časové okno: 0-16 weeks
|
Patient and Physician (PI) Assessments both range from 0-10 with 10 being the most disease activity
|
0-16 weeks
|
Modified Health Assessment Questionnaire (MHAQ)
Časové okno: 0-16 weeks
|
Modified Health Assessment Questionnaire (MHAQ) 0-8 with 8 being the most activity
|
0-16 weeks
|
Duration of Morning Stiffness in Joints
Časové okno: 0-16 weeks
|
Duration of morning stiffness in the joints, in minutes.
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0-16 weeks
|
CDAI
Časové okno: 0-16 weeks
|
Clinical Disease Activity Index (CDAI) 0-76 mm.
Interpretation of CDAI scores < 2.8 indicate remission; >2.8 and <= 10 indicates low disease activity; >10 and <= 22 indicates moderate disease activity; >22 indicates high disease activity.
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0-16 weeks
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Vital Signs-Temperature
Časové okno: 0-16 weeks
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0-16 weeks
|
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Vital Sign - Pulse
Časové okno: 0-16 weeks
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heartbeats per minute
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0-16 weeks
|
Weight
Časové okno: 0-16 weeks
|
Weight in kg
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0-16 weeks
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Vitals - Blood Pressure
Časové okno: 0 weeks and 16 weeks
|
measurement of blood pressure (mmHg)
|
0 weeks and 16 weeks
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Vitals - Respirations
Časové okno: 0 weeks and 16 weeks
|
Respirations represents breaths per minute
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0 weeks and 16 weeks
|
Spolupracovníci a vyšetřovatelé
Vyšetřovatelé
- Vrchní vyšetřovatel: Arnold E Postlethwaite, MD, Memphis VA Medical Center, Memphis, TN
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia
Primární dokončení (Aktuální)
Dokončení studie (Aktuální)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Odhad)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
Další identifikační čísla studie
- IMMA-007-08S
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