- ICH GCP
- US-Register für klinische Studien
- Klinische 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
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
Detaillierte Beschreibung
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.
Studientyp
Einschreibung (Tatsächlich)
Phase
- Phase 1
Kontakte und Standorte
Studienorte
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Tennessee
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Memphis, Tennessee, Vereinigte Staaten, 38104
- Memphis VA Medical Center, Memphis, TN
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Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
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.
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Zufällig
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Vervierfachen
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
---|---|
Experimental: 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.
|
Experimental: 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.
|
Experimental: 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.
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
---|---|---|
Number and Percent of Participants With Reduction of Immunity to Collagen Type-II After APLA-12 Treatment.
Zeitfenster: 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
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
---|---|---|
Flow Cytometry
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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.
Zeitfenster: 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
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Eosinophils
Zeitfenster: Baseline and 16 weeks
|
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
|
Baseline and 16 weeks
|
Laboratory Results of A12 vs Placebo: Lymphocytes
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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)
Zeitfenster: 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
|
Red Blood Cell Distribution Width (RDW)
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 0-16 weeks
|
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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 0-16 weeks
|
0-16 weeks
|
|
Patient Global Assessment (PGA) and Physician Global Assessment
Zeitfenster: 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)
Zeitfenster: 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
Zeitfenster: 0-16 weeks
|
Duration of morning stiffness in the joints, in minutes.
|
0-16 weeks
|
CDAI
Zeitfenster: 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
|
Vital Signs-Temperature
Zeitfenster: 0-16 weeks
|
0-16 weeks
|
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Vital Sign - Pulse
Zeitfenster: 0-16 weeks
|
heartbeats per minute
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0-16 weeks
|
Weight
Zeitfenster: 0-16 weeks
|
Weight in kg
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0-16 weeks
|
Vitals - Blood Pressure
Zeitfenster: 0 weeks and 16 weeks
|
measurement of blood pressure (mmHg)
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0 weeks and 16 weeks
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Vitals - Respirations
Zeitfenster: 0 weeks and 16 weeks
|
Respirations represents breaths per minute
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0 weeks and 16 weeks
|
Mitarbeiter und Ermittler
Ermittler
- Hauptermittler: Arnold E Postlethwaite, MD, Memphis VA Medical Center, Memphis, TN
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn
Primärer Abschluss (Tatsächlich)
Studienabschluss (Tatsächlich)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Schätzen)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Zusätzliche relevante MeSH-Bedingungen
Andere Studien-ID-Nummern
- IMMA-007-08S
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