Rheumatoid Arthritis
Conditions
Brief summary
This is a Phase I clinical trial to determine whether orally administered APL A12 at one or more doses is superior to placebo in effecting a 25% reduction in interferon (IFN) stimulation index in 1(II)-stimulated culture of peripheral blood mononuclear (PBMC) obtained from patients with Rheumatoid Arthritis (RA), which will be the primary outcome variable. In an effort to learn more about the mechanism of action of APL A12, the investigators will assess Th1/Th2/Th3 cytokine production in supernatants from 48h and 144h cultures of PBMC stimulated by 1(II) and by APL A12 above. The investigators will assess function of CD4+ CD25+ T regs to determine whether APL A12 improves their suppressive function. Flow cytometry combined with intracellular cytokine staining will be used in an effort to determine which T cell subset(s) is/are experiencing shifts in cytokine expression.
Detailed description
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.
Interventions
DRUGAPLA12
Intervention: Drug treatment will be stopped or interrupted if indicated. Medical care will be provided at no cost to the patient.
DRUGPlacebo
Drug treatment will be stopped or interrupted if indicated. Medical care will be provided at no cost to the patient.
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number and Percent of Participants With Reduction of Immunity to Collagen Type-II After APLA-12 Treatment. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Disease Activity Index (CDAI) at 0 and 16 Weeks Follow up | 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. |
| Change in Cytokine Profile From Baseline and 16 Weeks | 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. |
| Change in IgG and IgA Immunoglobulin From Baseline to 8 or 16 Weeks | baseline and 8 or 16 wks | The change was computed between baseline and 8 or 16 weeks, whichever was available. |
| Neutrophils Counts at 0 and 16 Weeks | 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 |
| A12 Treated vs Placebo of Monocytes. | 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 |
| Eosinophils | 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 |
| Laboratory Results of A12 vs Placebo: Lymphocytes | 0-16 weeks | Measure to determine whether APL has any effect on routine blood counts, chemistries, electrolytes, immunoglobulin to measure potential toxicities |
| Laboratory Results of A12 vs Placebo: Basophils | Baseline and 16 weeks | Measure to determine whether APL has any effect on routine blood counts, chemistries, electrolytes, immunoglobulin to measure potential toxicities |
| Hematocrit | 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 |
| Laboratory Results of A12 vs Placebo-Total Immunoglobulin (Immature Granulocytes) | Baseline and 16 weeks | Measure to determine whether APL has any effect on routine blood counts, chemistries, electrolytes, immunoglobulin to measure potential toxicities |
| Red Blood Cell Distribution Width (RDW) | 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 |
| Hemaglobin | 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 |
| Red Blood Cells | 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 |
| White Blood Count | 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 |
| Platelets | 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 |
| AST, ALT and Alkaline Phosphatase | 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 |
| Flow Cytometry | 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. |
| Sodium, Potassium and Chloride | 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 |
| Total Protein, Albumin | 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 |
| C-reactive Protein | 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 |
| Rheumatoid Factor | 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 |
| Sedimentation Rate | 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 |
| Laboratory Results of A12 vs Placebo Anti-CCP Antibody | 0-16 weeks | — |
| Patient Global Assessment (PGA) and Physician Global Assessment | 0-16 weeks | Patient and Physician (PI) Assessments both range from 0-10 with 10 being the most disease activity |
| Modified Health Assessment Questionnaire (MHAQ) | 0-16 weeks | Modified Health Assessment Questionnaire (MHAQ) 0-8 with 8 being the most activity |
| Duration of Morning Stiffness in Joints | 0-16 weeks | Duration of morning stiffness in the joints, in minutes. |
| CDAI | 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. |
| Vital Signs-Temperature | 0-16 weeks | — |
| Vital Sign - Pulse | 0-16 weeks | heartbeats per minute |
| Weight | 0-16 weeks | Weight in kg |
| Vitals - Blood Pressure | 0 weeks and 16 weeks | measurement of blood pressure (mmHg) |
| Vitals - Respirations | 0 weeks and 16 weeks | Respirations represents breaths per minute |
| Ca, BUN, Glucose,Creatinine, Total Bilirubin | 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 |
Countries
United States
Participant flow
Recruitment details
October 1, 2009-September 30, 2015.
Participants by arm
| Arm | Count |
|---|---|
| 30 or 50 ug APL/Day 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 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 micrograms) or placebo (Block 1). We will begin with the lowest dose (30 micrograms/day) and enroll 6 to receive 30 micrograms/day APL A12 and 2 to receive placebo for 16 weeks. Results will be reported to the DMC for a decision to proceed to the next block based on indications of safety APL A12: IND 103860: The study drug APL A12 is a man made (or synthesized) fragment similar to a portion of natural type II collagen, the major collagen found in joint cartilage. Cartilage is the tough, elastic tissue found in | 14 |
| Placebo 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.
APL A12: IND 103860: The study drug APL A12 is a man made (or synthesized) fragment similar to a portion of natural type II collagen, the major collagen found in joint cartilage. Cartilage is the tough, elastic tissue found in various parts of the body, including the joints. The best dose of APL A12 to use in patients with rheumatoid arthritis is not known. | 8 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | began prohibitive drug | 0 | 0 | 1 |
| Overall Study | Medication for RA had to be changed | 1 | 0 | 0 |
| Overall Study | new illness | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | 30 or 50 ug APL/Day | Total | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 4 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 18 Participants | 8 Participants |
| Age, Continuous | 62.08 years STANDARD_DEVIATION 8.47 | 63.94 years STANDARD_DEVIATION 8.88 | 65.8 years STANDARD_DEVIATION 9.91 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 22 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Immunity to Type-II collagen and in vitro decrease by APL12 | 12 Participants | 17 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 7 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 15 Participants | 7 Participants |
| Region of Enrollment United States | 14 Participants | 22 Participants | 8 Participants |
| Sex: Female, Male Female | 5 Participants | 6 Participants | 1 Participants |
| Sex: Female, Male Male | 9 Participants | 16 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 14 | 0 / 8 |
| other Total, other adverse events | 8 / 14 | 6 / 8 |
| serious Total, serious adverse events | 2 / 14 | 0 / 8 |
Outcome results
Primary
Number and Percent of Participants With Reduction of Immunity to Collagen Type-II After APLA-12 Treatment.
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.
Time frame: 16 weeks
Population: We could not analyze all the patients due to adverse events, drop outs or not all participants had data available for all measurements
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| APL 30 and 50ug/Day | Number and Percent of Participants With Reduction of Immunity to Collagen Type-II After APLA-12 Treatment. | 9 Participants |
| Placebo | Number and Percent of Participants With Reduction of Immunity to Collagen Type-II After APLA-12 Treatment. | 4 Participants |
Comparison: Specified to be a reduction from baseline values of net IFNƔ concentration of ≥ 25% in αl(ll)-stimulated PBMC culture supernatants (calculated as αI(II)-IFNƔ-PBS IFNƔ in patients receiving APL A12 compared to placebo.p-value: 0.5179Fisher Exact
p-value: 0.0114Exact Test
p-value: 0.4142Exact Test
Secondary
A12 Treated vs Placebo of Monocytes.
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
Time frame: Baseline and 16 wks
Population: We could not analyze all the patients due to adverse events, drop outs or not all participants had data available for all measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL 30 and 50ug/Day | A12 Treated vs Placebo of Monocytes. | Baseline | 9.1 percent of total white blood cells | Standard Error 0.7 |
| APL 30 and 50ug/Day | A12 Treated vs Placebo of Monocytes. | 16 weeks | 8.93 percent of total white blood cells | Standard Error 0.7 |
| Placebo | A12 Treated vs Placebo of Monocytes. | Baseline | 9.25 percent of total white blood cells | Standard Error 0.9 |
| Placebo | A12 Treated vs Placebo of Monocytes. | 16 weeks | 7.53 percent of total white blood cells | Standard Error 1 |
Secondary
AST, ALT and Alkaline Phosphatase
Laboratory Results of A12 vs Placebo to determine whether APL has any effect on routine blood counts, chemistries, electrolytes, immunoglobulin to measure potential toxicities
Time frame: 0-16 weeks
Population: We could not analyze all the patients due to adverse events, drop outs or not all participants had data available for all measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL 30 and 50ug/Day | AST, ALT and Alkaline Phosphatase | 0 week-AST | 32.29 IU/L | Standard Error 3.36 |
| APL 30 and 50ug/Day | AST, ALT and Alkaline Phosphatase | 16 week AST | 31.61 IU/L | Standard Error 3.67 |
| APL 30 and 50ug/Day | AST, ALT and Alkaline Phosphatase | 0 week ALT | 28.8 IU/L | Standard Error 3.2 |
| APL 30 and 50ug/Day | AST, ALT and Alkaline Phosphatase | 16 week ALT | 26.21 IU/L | Standard Error 3.33 |
| APL 30 and 50ug/Day | AST, ALT and Alkaline Phosphatase | 0 week alkaline phos | 97.79 IU/L | Standard Error 5.05 |
| APL 30 and 50ug/Day | AST, ALT and Alkaline Phosphatase | 16 week alkaline phos | 86.64 IU/L | Standard Error 5.34 |
| Placebo | AST, ALT and Alkaline Phosphatase | 0 week alkaline phos | 70.75 IU/L | Standard Error 6.13 |
| Placebo | AST, ALT and Alkaline Phosphatase | 0 week-AST | 39.75 IU/L | Standard Error 3.97 |
| Placebo | AST, ALT and Alkaline Phosphatase | 16 week ALT | 35.62 IU/L | Standard Error 4.24 |
| Placebo | AST, ALT and Alkaline Phosphatase | 16 week AST | 33.52 IU/L | Standard Error 4.52 |
| Placebo | AST, ALT and Alkaline Phosphatase | 16 week alkaline phos | 73.07 IU/L | Standard Error 6.72 |
| Placebo | AST, ALT and Alkaline Phosphatase | 0 week ALT | 35.75 IU/L | Standard Error 3.94 |
Secondary
Ca, BUN, Glucose,Creatinine, Total Bilirubin
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
Time frame: 0-16 weeks
Population: We could not analyze all the patients due to adverse events, drop outs or not all participants had data available for all measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL 30 and 50ug/Day | Ca, BUN, Glucose,Creatinine, Total Bilirubin | 0 week calcium | 9.35 mg/dl | Standard Error 0.09 |
| APL 30 and 50ug/Day | Ca, BUN, Glucose,Creatinine, Total Bilirubin | 16 week calcium | 9.2 mg/dl | Standard Error 0.1 |
| APL 30 and 50ug/Day | Ca, BUN, Glucose,Creatinine, Total Bilirubin | 0 week BUN | 15.7 mg/dl | Standard Error 2.37 |
| APL 30 and 50ug/Day | Ca, BUN, Glucose,Creatinine, Total Bilirubin | 16 week BUN | 17.32 mg/dl | Standard Error 2.45 |
| APL 30 and 50ug/Day | Ca, BUN, Glucose,Creatinine, Total Bilirubin | 0 week glucose | 109.4 mg/dl | Standard Error 9.71 |
| APL 30 and 50ug/Day | Ca, BUN, Glucose,Creatinine, Total Bilirubin | 16 week glucose | 92.67 mg/dl | Standard Error 10.2 |
| APL 30 and 50ug/Day | Ca, BUN, Glucose,Creatinine, Total Bilirubin | 0 week total bilirubin | 0.68 mg/dl | Standard Error 0.067 |
| APL 30 and 50ug/Day | Ca, BUN, Glucose,Creatinine, Total Bilirubin | 16 week total bilirubin | 0.53 mg/dl | Standard Error 0.7 |
| APL 30 and 50ug/Day | Ca, BUN, Glucose,Creatinine, Total Bilirubin | 0 week creatinine | 0.945 mg/dl | Standard Error 0.208 |
| APL 30 and 50ug/Day | Ca, BUN, Glucose,Creatinine, Total Bilirubin | 16 week creatinine | 1.0050 mg/dl | Standard Error 22.96 |
| Placebo | Ca, BUN, Glucose,Creatinine, Total Bilirubin | 16 week total bilirubin | 0.75 mg/dl | Standard Error 0.088 |
| Placebo | Ca, BUN, Glucose,Creatinine, Total Bilirubin | 0 week calcium | 9.11 mg/dl | Standard Error 0.11 |
| Placebo | Ca, BUN, Glucose,Creatinine, Total Bilirubin | 16 week glucose | 86.72 mg/dl | Standard Error 12.9 |
| Placebo | Ca, BUN, Glucose,Creatinine, Total Bilirubin | 16 week calcium | 9.22 mg/dl | Standard Error 0.12 |
| Placebo | Ca, BUN, Glucose,Creatinine, Total Bilirubin | 16 week creatinine | 0.8501 mg/dl | Standard Error 0.2818 |
| Placebo | Ca, BUN, Glucose,Creatinine, Total Bilirubin | 0 week BUN | 15.37 mg/dl | Standard Error 2.93 |
| Placebo | Ca, BUN, Glucose,Creatinine, Total Bilirubin | 0 week total bilirubin | 0.63 mg/dl | Standard Error 0.082 |
| Placebo | Ca, BUN, Glucose,Creatinine, Total Bilirubin | 16 week BUN | 15.56 mg/dl | Standard Error 3.13 |
| Placebo | Ca, BUN, Glucose,Creatinine, Total Bilirubin | 0 week creatinine | 0.811 mg/dl | Standard Error 0.244 |
| Placebo | Ca, BUN, Glucose,Creatinine, Total Bilirubin | 0 week glucose | 112.4 mg/dl | Standard Error 11.9 |
Secondary
CDAI
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.
Time frame: 0-16 weeks
Population: We could not analyze all the patients due to adverse events, drop outs or not all participants had data available for all measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL 30 and 50ug/Day | CDAI | 0 week CDAI | 10 centimeters | Standard Error 2 |
| APL 30 and 50ug/Day | CDAI | 16 week CDAI | 9.9 centimeters | Standard Error 2.2 |
| Placebo | CDAI | 0 week CDAI | 10.3 centimeters | Standard Error 3.3 |
| Placebo | CDAI | 16 week CDAI | 12.8 centimeters | Standard Error 3 |
Secondary
Change in Cytokine Profile From Baseline 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.
Time frame: 0 and 16 weeks
Population: We could not analyze all the patients due to adverse events, drop outs or not all participants had data available for all measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL 30 and 50ug/Day | Change in Cytokine Profile From Baseline and 16 Weeks | IL-1B | 617.1 absolute change (picograms/milliliter) | Standard Deviation 2111.8 |
| APL 30 and 50ug/Day | Change in Cytokine Profile From Baseline and 16 Weeks | IL-17A | -104.2 absolute change (picograms/milliliter) | Standard Deviation 229.9 |
| APL 30 and 50ug/Day | Change in Cytokine Profile From Baseline and 16 Weeks | IL-5 | 5.19 absolute change (picograms/milliliter) | Standard Deviation 19.11 |
| APL 30 and 50ug/Day | Change in Cytokine Profile From Baseline and 16 Weeks | IL-6 | -2002.9 absolute change (picograms/milliliter) | Standard Deviation 10752.9 |
| APL 30 and 50ug/Day | Change in Cytokine Profile From Baseline and 16 Weeks | IL-9 | 196.1 absolute change (picograms/milliliter) | Standard Deviation 679.2 |
| APL 30 and 50ug/Day | Change in Cytokine Profile From Baseline and 16 Weeks | TNFa | -7.50 absolute change (picograms/milliliter) | Standard Deviation 39.98 |
| APL 30 and 50ug/Day | Change in Cytokine Profile From Baseline and 16 Weeks | IL-13 | -6.46 absolute change (picograms/milliliter) | Standard Deviation 17.12 |
| APL 30 and 50ug/Day | Change in Cytokine Profile From Baseline and 16 Weeks | IL-21 | -4.32 absolute change (picograms/milliliter) | Standard Deviation 10.92 |
| APL 30 and 50ug/Day | Change in Cytokine Profile From Baseline and 16 Weeks | TGF-B1 | 0.12 absolute change (picograms/milliliter) | Standard Deviation 0.42 |
| APL 30 and 50ug/Day | Change in Cytokine Profile From Baseline and 16 Weeks | MIP3A(CCL-20) | -36.39 absolute change (picograms/milliliter) | Standard Deviation 89.6 |
| APL 30 and 50ug/Day | Change in Cytokine Profile From Baseline and 16 Weeks | IL-10 | -22.51 absolute change (picograms/milliliter) | Standard Deviation 82.57 |
| Placebo | Change in Cytokine Profile From Baseline and 16 Weeks | MIP3A(CCL-20) | 3.60 absolute change (picograms/milliliter) | Standard Deviation 21.08 |
| Placebo | Change in Cytokine Profile From Baseline and 16 Weeks | IL-10 | -4.70 absolute change (picograms/milliliter) | Standard Deviation 5.99 |
| Placebo | Change in Cytokine Profile From Baseline and 16 Weeks | IL-13 | -0.83 absolute change (picograms/milliliter) | Standard Deviation 4.57 |
| Placebo | Change in Cytokine Profile From Baseline and 16 Weeks | IL-5 | -2.42 absolute change (picograms/milliliter) | Standard Deviation 2.34 |
| Placebo | Change in Cytokine Profile From Baseline and 16 Weeks | IL-1B | 45.64 absolute change (picograms/milliliter) | Standard Deviation 280.1 |
| Placebo | Change in Cytokine Profile From Baseline and 16 Weeks | IL-9 | -45.37 absolute change (picograms/milliliter) | Standard Deviation 56.1 |
| Placebo | Change in Cytokine Profile From Baseline and 16 Weeks | TGF-B1 | -0.06 absolute change (picograms/milliliter) | Standard Deviation 0.41 |
| Placebo | Change in Cytokine Profile From Baseline and 16 Weeks | IL-17A | 5.4091 absolute change (picograms/milliliter) | Standard Deviation 7.4381 |
| Placebo | Change in Cytokine Profile From Baseline and 16 Weeks | IL-6 | 3.97 absolute change (picograms/milliliter) | Standard Deviation 261.4 |
| Placebo | Change in Cytokine Profile From Baseline and 16 Weeks | TNFa | 0.30 absolute change (picograms/milliliter) | Standard Deviation 4.14 |
| Placebo | Change in Cytokine Profile From Baseline and 16 Weeks | IL-21 | 218.3 absolute change (picograms/milliliter) | Standard Deviation 492.9 |
p-value: >0.05t-test, 2 sided
Secondary
Change in IgG and IgA Immunoglobulin From Baseline to 8 or 16 Weeks
The change was computed between baseline and 8 or 16 weeks, whichever was available.
Time frame: baseline and 8 or 16 wks
Population: Some participants only had measurable data at 8 weeks, or dropped out before 16 weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL 30 and 50ug/Day | Change in IgG and IgA Immunoglobulin From Baseline to 8 or 16 Weeks | change in IgG | 1047.01 absolute change (followup-baseline) ng/m | Standard Deviation 3570.28 |
| APL 30 and 50ug/Day | Change in IgG and IgA Immunoglobulin From Baseline to 8 or 16 Weeks | change in IgA | 3410.3 absolute change (followup-baseline) ng/m | Standard Deviation 11339.8 |
| Placebo | Change in IgG and IgA Immunoglobulin From Baseline to 8 or 16 Weeks | change in IgG | 11.43 absolute change (followup-baseline) ng/m | Standard Deviation 109.27 |
| Placebo | Change in IgG and IgA Immunoglobulin From Baseline to 8 or 16 Weeks | change in IgA | 103.69 absolute change (followup-baseline) ng/m | Standard Deviation 233.92 |
Secondary
Clinical Disease Activity Index (CDAI) at 0 and 16 Weeks Follow up
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.
Time frame: 0 and16 weeks
Population: We could not analyze all the patients due to adverse events, drop outs or not all participants had data available for all measurements
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| APL 30 and 50ug/Day | Clinical Disease Activity Index (CDAI) at 0 and 16 Weeks Follow up | CDAI at 0 weeks | 10.0333 disease activity score |
| APL 30 and 50ug/Day | Clinical Disease Activity Index (CDAI) at 0 and 16 Weeks Follow up | CDAI at 16 weeks | 9.8778 disease activity score |
| Placebo | Clinical Disease Activity Index (CDAI) at 0 and 16 Weeks Follow up | CDAI at 0 weeks | 10.3271 disease activity score |
| Placebo | Clinical Disease Activity Index (CDAI) at 0 and 16 Weeks Follow up | CDAI at 16 weeks | 12.8000 disease activity score |
p-value: >0.05Mixed Models Analysis
Secondary
C-reactive Protein
Laboratory Results of A12 vs Placebo to determine whether APL has any effect on routine blood counts, chemistries, electrolytes, immunoglobulin to measure potential toxicities
Time frame: 0-16 weeks
Population: We could not analyze all the patients due to adverse events, drop outs or not all participants had data available for all measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL 30 and 50ug/Day | C-reactive Protein | 0 week CRP | 11.8 mg/L | Standard Error 3.13 |
| APL 30 and 50ug/Day | C-reactive Protein | 16 week CRP | 11.38 mg/L | Standard Error 3.07 |
| Placebo | C-reactive Protein | 0 week CRP | 10.57 mg/L | Standard Error 4.61 |
| Placebo | C-reactive Protein | 16 week CRP | 8 mg/L | Standard Error 4.61 |
Secondary
Duration of Morning Stiffness in Joints
Duration of morning stiffness in the joints, in minutes.
Time frame: 0-16 weeks
Population: We could not analyze all the patients due to adverse events, drop outs or not all participants had data available for all measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL 30 and 50ug/Day | Duration of Morning Stiffness in Joints | 0 week stiffness | 64.49 minutes | Standard Error 98.81 |
| APL 30 and 50ug/Day | Duration of Morning Stiffness in Joints | 16 week stiffness | 184.44 minutes | Standard Error 93.48 |
| Placebo | Duration of Morning Stiffness in Joints | 0 week stiffness | 38.75 minutes | Standard Error 140.22 |
| Placebo | Duration of Morning Stiffness in Joints | 16 week stiffness | 54.78 minutes | Standard Error 195.3 |
Secondary
Eosinophils
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
Time frame: Baseline and 16 weeks
Population: We could not analyze all the patients due to adverse events, drop outs or not all participants had data available for all measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL 30 and 50ug/Day | Eosinophils | Baseline | 2.29 percent in total white blood cells | Standard Error 0.5 |
| APL 30 and 50ug/Day | Eosinophils | 16 weeks | 2.69 percent in total white blood cells | Standard Error 0.6 |
| Placebo | Eosinophils | Baseline | 4.4 percent in total white blood cells | Standard Error 0.7 |
| Placebo | Eosinophils | 16 weeks | 4.11 percent in total white blood cells | Standard Error 0.7 |
Secondary
Flow Cytometry
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.
Time frame: baseline and 8 or 16 weeks
Population: Not all participants had data available for all measurements.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL 30 and 50ug/Day | Flow Cytometry | CD4+IL-4+ | 0.8959 percent change in number of cells | Standard Deviation 1.0736 |
| APL 30 and 50ug/Day | Flow Cytometry | CD4+CD25hi+FoxP3 | 3.4240 percent change in number of cells | Standard Deviation 4.3569 |
| APL 30 and 50ug/Day | Flow Cytometry | CD4+IL-17+ | 1.5299 percent change in number of cells | Standard Deviation 4.1486 |
| APL 30 and 50ug/Day | Flow Cytometry | CD4+IL-10+ | 0.1735 percent change in number of cells | Standard Deviation 0.54 |
| Placebo | Flow Cytometry | CD4+IL-10+ | 0.3385 percent change in number of cells | Standard Deviation 0.4444 |
| Placebo | Flow Cytometry | CD4+IL-4+ | 1.9400 percent change in number of cells | Standard Deviation 2.8626 |
| Placebo | Flow Cytometry | CD4+IL-17+ | -0.4230 percent change in number of cells | Standard Deviation 2.1367 |
| Placebo | Flow Cytometry | CD4+CD25hi+FoxP3 | 0.9600 percent change in number of cells | Standard Deviation 3.439 |
Secondary
Hemaglobin
Laboratory Results of A12 vs Placebo to determine whether APL has any effect on routine blood counts, chemistries, electrolytes, immunoglobulin to measure potential toxicities
Time frame: Baseline and 16 weeks
Population: We could not analyze all the patients due to adverse events, drop outs or not all participants had data available for all measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL 30 and 50ug/Day | Hemaglobin | Baseline -Hgb | 13.66 grams/deciliter | Standard Error 0.29 |
| APL 30 and 50ug/Day | Hemaglobin | 16 week Hgb | 13.31 grams/deciliter | Standard Error 0.3 |
| Placebo | Hemaglobin | Baseline -Hgb | 14.23 grams/deciliter | Standard Error 0.38 |
| Placebo | Hemaglobin | 16 week Hgb | 14.31 grams/deciliter | Standard Error 0.4 |
Secondary
Hematocrit
Laboratory Results of A12 vs Placebo to determine whether APL has any effect on routine blood counts, chemistries, electrolytes, immunoglobulin to measure potential toxicities
Time frame: 0-16 weeks
Population: We could not analyze all the patients due to adverse events, drop outs or not all participants had data available for all measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL 30 and 50ug/Day | Hematocrit | 0 week HCT | 40.63 ratio of RBC to total blood cells/volume | Standard Error 0.85 |
| APL 30 and 50ug/Day | Hematocrit | 16 week HCT | 39.69 ratio of RBC to total blood cells/volume | Standard Error 0.9 |
| Placebo | Hematocrit | 0 week HCT | 42 ratio of RBC to total blood cells/volume | Standard Error 1.13 |
| Placebo | Hematocrit | 16 week HCT | 42.6 ratio of RBC to total blood cells/volume | Standard Error 1.19 |
Secondary
Laboratory Results of A12 vs Placebo Anti-CCP Antibody
Time frame: 0-16 weeks
Population: We could not analyze all the patients due to adverse events, drop outs or not all participants had data available for all measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL 30 and 50ug/Day | Laboratory Results of A12 vs Placebo Anti-CCP Antibody | 0 week anti CCP | 310.6 IU/mL | Standard Error 35.2 |
| APL 30 and 50ug/Day | Laboratory Results of A12 vs Placebo Anti-CCP Antibody | 16 week anti CCP | 319.07 IU/mL | Standard Error 35.63 |
| Placebo | Laboratory Results of A12 vs Placebo Anti-CCP Antibody | 0 week anti CCP | 127.54 IU/mL | Standard Error 44.9 |
| Placebo | Laboratory Results of A12 vs Placebo Anti-CCP Antibody | 16 week anti CCP | 120.9 IU/mL | Standard Error 45.52 |
Secondary
Laboratory Results of A12 vs Placebo: Basophils
Measure to determine whether APL has any effect on routine blood counts, chemistries, electrolytes, immunoglobulin to measure potential toxicities
Time frame: Baseline and 16 weeks
Population: We could not analyze all the patients due to adverse events, drop outs or not all participants had data available for all measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL 30 and 50ug/Day | Laboratory Results of A12 vs Placebo: Basophils | 0 week-Basophils | 0.53 percent in total white blood cells/ml | Standard Error 0.09 |
| APL 30 and 50ug/Day | Laboratory Results of A12 vs Placebo: Basophils | 16 week Basophils | 0.67 percent in total white blood cells/ml | Standard Error 0.097 |
| Placebo | Laboratory Results of A12 vs Placebo: Basophils | 0 week-Basophils | 0.6 percent in total white blood cells/ml | Standard Error 0.12 |
| Placebo | Laboratory Results of A12 vs Placebo: Basophils | 16 week Basophils | 0.47 percent in total white blood cells/ml | Standard Error 0.13 |
Secondary
Laboratory Results of A12 vs Placebo: Lymphocytes
Measure to determine whether APL has any effect on routine blood counts, chemistries, electrolytes, immunoglobulin to measure potential toxicities
Time frame: 0-16 weeks
Population: We could not analyze all the patients due to adverse events, drop outs or not all participants had data available for all measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL 30 and 50ug/Day | Laboratory Results of A12 vs Placebo: Lymphocytes | 0 Week Lymphocytes | 26.92 percent in total white blood cells/ml | Standard Error 2.22 |
| APL 30 and 50ug/Day | Laboratory Results of A12 vs Placebo: Lymphocytes | 16 weeks Lymphocytes | 28.2 percent in total white blood cells/ml | Standard Error 2.35 |
| Placebo | Laboratory Results of A12 vs Placebo: Lymphocytes | 0 Week Lymphocytes | 25.41 percent in total white blood cells/ml | Standard Error 2.94 |
| Placebo | Laboratory Results of A12 vs Placebo: Lymphocytes | 16 weeks Lymphocytes | 25.37 percent in total white blood cells/ml | Standard Error 3.1 |
Secondary
Laboratory Results of A12 vs Placebo-Total Immunoglobulin (Immature Granulocytes)
Measure to determine whether APL has any effect on routine blood counts, chemistries, electrolytes, immunoglobulin to measure potential toxicities
Time frame: Baseline and 16 weeks
Population: We could not analyze all the patients due to adverse events, drop outs or not all participants had data available for all measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL 30 and 50ug/Day | Laboratory Results of A12 vs Placebo-Total Immunoglobulin (Immature Granulocytes) | 0 week-IG | 0.3 grams per deciliter | Standard Error 0.05 |
| APL 30 and 50ug/Day | Laboratory Results of A12 vs Placebo-Total Immunoglobulin (Immature Granulocytes) | 16 week-IG | 0.3 grams per deciliter | Standard Error 0.05 |
| Placebo | Laboratory Results of A12 vs Placebo-Total Immunoglobulin (Immature Granulocytes) | 0 week-IG | 0.24 grams per deciliter | Standard Error 0.06 |
| Placebo | Laboratory Results of A12 vs Placebo-Total Immunoglobulin (Immature Granulocytes) | 16 week-IG | 0.33 grams per deciliter | Standard Error 0.07 |
Secondary
Modified Health Assessment Questionnaire (MHAQ)
Modified Health Assessment Questionnaire (MHAQ) 0-8 with 8 being the most activity
Time frame: 0-16 weeks
Population: We could not analyze all the patients due to adverse events, drop outs or not all participants had data available for all measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL 30 and 50ug/Day | Modified Health Assessment Questionnaire (MHAQ) | 0 week MHAQ | 3.44 MHAQ units on a scale | Standard Error 1.14 |
| APL 30 and 50ug/Day | Modified Health Assessment Questionnaire (MHAQ) | 16 week MHAQ | 4 MHAQ units on a scale | Standard Error 1.14 |
| Placebo | Modified Health Assessment Questionnaire (MHAQ) | 0 week MHAQ | 1.75 MHAQ units on a scale | Standard Error 1.71 |
| Placebo | Modified Health Assessment Questionnaire (MHAQ) | 16 week MHAQ | 2.5 MHAQ units on a scale | Standard Error 1.9 |
Secondary
Neutrophils Counts at 0 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
Time frame: Baseline and 16 weeks
Population: We could not analyze all the patients due to adverse events, drop outs or not all participants had data available for all measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL 30 and 50ug/Day | Neutrophils Counts at 0 and 16 Weeks | 0 weeks Neutrophils | 60.9 percent of total number of blood cells | Standard Error 2.4 |
| APL 30 and 50ug/Day | Neutrophils Counts at 0 and 16 Weeks | 16 weeks Neutrophils | 59.2 percent of total number of blood cells | Standard Error 2.6 |
| Placebo | Neutrophils Counts at 0 and 16 Weeks | 0 weeks Neutrophils | 60 percent of total number of blood cells | Standard Error 3.2 |
| Placebo | Neutrophils Counts at 0 and 16 Weeks | 16 weeks Neutrophils | 62.4 percent of total number of blood cells | Standard Error 3.5 |
Secondary
Patient Global Assessment (PGA) and Physician Global Assessment
Patient and Physician (PI) Assessments both range from 0-10 with 10 being the most disease activity
Time frame: 0-16 weeks
Population: We could not analyze all the patients due to adverse events, drop outs or not all participants had data available for all measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL 30 and 50ug/Day | Patient Global Assessment (PGA) and Physician Global Assessment | 16 week PI Assessment | 2.77 score on a scale | Standard Error 0.5 |
| APL 30 and 50ug/Day | Patient Global Assessment (PGA) and Physician Global Assessment | 0 week PI Assessment | 2.6 score on a scale | Standard Error 0.46 |
| APL 30 and 50ug/Day | Patient Global Assessment (PGA) and Physician Global Assessment | 0 week Patient Assessment | 3.99 score on a scale | Standard Error 0.52 |
| APL 30 and 50ug/Day | Patient Global Assessment (PGA) and Physician Global Assessment | 16 week Patient Assessment | 4.7 score on a scale | Standard Error 0.59 |
| Placebo | Patient Global Assessment (PGA) and Physician Global Assessment | 16 week Patient Assessment | 3.75 score on a scale | Standard Error 0.78 |
| Placebo | Patient Global Assessment (PGA) and Physician Global Assessment | 0 week Patient Assessment | 4.8 score on a scale | Standard Error 0.9 |
| Placebo | Patient Global Assessment (PGA) and Physician Global Assessment | 0 week PI Assessment | 3.26 score on a scale | Standard Error 0.77 |
| Placebo | Patient Global Assessment (PGA) and Physician Global Assessment | 16 week PI Assessment | 4.3 score on a scale | Standard Error 0.7 |
Secondary
Platelets
Laboratory Results of A12 vs Placebo to determine whether APL has any effect on routine blood counts, chemistries, electrolytes, immunoglobulin to measure potential toxicities
Time frame: 0-16 weeks
Population: We could not analyze all the patients due to adverse events, drop outs or not all participants had data available for all measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL 30 and 50ug/Day | Platelets | 0 week Platelet | 248.71 10^3 cells/uL | Standard Error 14.81 |
| APL 30 and 50ug/Day | Platelets | 16 week Platelet | 256.96 10^3 cells/uL | Standard Error 15.51 |
| Placebo | Platelets | 0 week Platelet | 224.5 10^3 cells/uL | Standard Error 19.6 |
| Placebo | Platelets | 16 week Platelet | 225.44 10^3 cells/uL | Standard Error 20.43 |
Secondary
Red Blood Cell Distribution Width (RDW)
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
Time frame: 0 and 16 weeks
Population: We could not analyze all the patients due to adverse events, drop outs or not all participants had data available for all measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL 30 and 50ug/Day | Red Blood Cell Distribution Width (RDW) | Baseline-RDW | 14.67 percent of mean corpuscular volume | Standard Error 0.31 |
| APL 30 and 50ug/Day | Red Blood Cell Distribution Width (RDW) | 16 week RDW | 14.8 percent of mean corpuscular volume | Standard Error 0.33 |
| Placebo | Red Blood Cell Distribution Width (RDW) | Baseline-RDW | 14.15 percent of mean corpuscular volume | Standard Error 0.41 |
| Placebo | Red Blood Cell Distribution Width (RDW) | 16 week RDW | 13.9 percent of mean corpuscular volume | Standard Error 0.43 |
Secondary
Red Blood Cells
Laboratory Results of A12 vs Placebo to determine whether APL has any effect on routine blood counts, chemistries, electrolytes, immunoglobulin to measure potential toxicities
Time frame: 0-16 weeks
Population: We could not analyze all the patients due to adverse events, drop outs or not all participants had data available for all measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL 30 and 50ug/Day | Red Blood Cells | 0 week RBC | 4.66 10^6 cells/uL | Standard Error 0.13 |
| APL 30 and 50ug/Day | Red Blood Cells | 16 week RBC | 4.6 10^6 cells/uL | Standard Error 0.13 |
| Placebo | Red Blood Cells | 0 week RBC | 4.49 10^6 cells/uL | Standard Error 0.17 |
| Placebo | Red Blood Cells | 16 week RBC | 4.57 10^6 cells/uL | Standard Error 0.17 |
Secondary
Rheumatoid Factor
Laboratory Results of A12 vs Placebo to determine whether APL has any effect on routine blood counts, chemistries, electrolytes, immunoglobulin to measure potential toxicities
Time frame: 0-16 weeks
Population: We could not analyze all the patients due to adverse events, drop outs or not all participants had data available for all measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL 30 and 50ug/Day | Rheumatoid Factor | 0 week RF | 36.72 IU/mL | Standard Error 9.4 |
| APL 30 and 50ug/Day | Rheumatoid Factor | 16 week RF | 25.29 IU/mL | Standard Error 9.4 |
| Placebo | Rheumatoid Factor | 0 week RF | 23.75 IU/mL | Standard Error 14.15 |
| Placebo | Rheumatoid Factor | 16 week RF | 23.35 IU/mL | Standard Error 14.15 |
Secondary
Sedimentation Rate
Laboratory results of A12 vs Placebo to determine whether APL has any effect on routine blood counts, chemistries, electrolytes, immunoglobulin to measure potential toxicities
Time frame: 0-16 weeks
Population: We could not analyze all the patients due to adverse events, drop outs or not all participants had data available for all measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL 30 and 50ug/Day | Sedimentation Rate | 0 week ESR | 30.85 mm/hr | Standard Error 5.13 |
| APL 30 and 50ug/Day | Sedimentation Rate | 16 week ESR | 33.5 mm/hr | Standard Error 5.29 |
| Placebo | Sedimentation Rate | 0 week ESR | 18.62 mm/hr | Standard Error 6.7 |
| Placebo | Sedimentation Rate | 16 week ESR | 20.26 mm/hr | Standard Error 6.9 |
Secondary
Sodium, Potassium and Chloride
Laboratory results of A12 vs Placebo to determine whether APL has any effect on routine blood counts, chemistries, electrolytes, immunoglobulin to measure potential toxicities
Time frame: 0-16 weeks
Population: We could not analyze all the patients due to adverse events, drop outs or not all participants had data available for all measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL 30 and 50ug/Day | Sodium, Potassium and Chloride | 0 week potassium | 3.9 mmol/L | Standard Error 0.16 |
| APL 30 and 50ug/Day | Sodium, Potassium and Chloride | 0 week sodium | 140.7 mmol/L | Standard Error 0.8 |
| APL 30 and 50ug/Day | Sodium, Potassium and Chloride | 16 week sodium | 141.46 mmol/L | Standard Error 0.84 |
| APL 30 and 50ug/Day | Sodium, Potassium and Chloride | 16 week potassium | 3.8 mmol/L | Standard Error 0.17 |
| APL 30 and 50ug/Day | Sodium, Potassium and Chloride | 0 week chloride | 102.9 mmol/L | Standard Error 0.73 |
| APL 30 and 50ug/Day | Sodium, Potassium and Chloride | 16 week chloride | 103.22 mmol/L | Standard Error 0.78 |
| Placebo | Sodium, Potassium and Chloride | 0 week chloride | 100.75 mmol/L | Standard Error 0.88 |
| Placebo | Sodium, Potassium and Chloride | 16 week potassium | 4.03 mmol/L | Standard Error 0.2 |
| Placebo | Sodium, Potassium and Chloride | 0 week sodium | 140.25 mmol/L | Standard Error 0.98 |
| Placebo | Sodium, Potassium and Chloride | 16 week chloride | 100.9 mmol/L | Standard Error 0.97 |
| Placebo | Sodium, Potassium and Chloride | 16 week sodium | 140.34 mmol/L | Standard Error 1.06 |
| Placebo | Sodium, Potassium and Chloride | 0 week potassium | 4 mmol/L | Standard Error 0.2 |
Secondary
Total Protein, Albumin
Laboratory Results of A12 vs Placebo to determine whether APL has any effect on routine blood counts, chemistries, electrolytes, immunoglobulin to measure potential toxicities
Time frame: 0-16 weeks
Population: We could not analyze all the patients due to adverse events, drop outs or not all participants had data available for all measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL 30 and 50ug/Day | Total Protein, Albumin | 0 week total protein | 7.75 g/dL | Standard Error 0.17 |
| APL 30 and 50ug/Day | Total Protein, Albumin | 16 week total protein | 7.16 g/dL | Standard Error 0.19 |
| APL 30 and 50ug/Day | Total Protein, Albumin | 0 week albumin | 4.18 g/dL | Standard Error 0.08 |
| APL 30 and 50ug/Day | Total Protein, Albumin | 16 week albumin | 4.16 g/dL | Standard Error 0.084 |
| Placebo | Total Protein, Albumin | 16 week albumin | 4.42 g/dL | Standard Error 0.11 |
| Placebo | Total Protein, Albumin | 0 week total protein | 7.64 g/dL | Standard Error 0.2 |
| Placebo | Total Protein, Albumin | 0 week albumin | 4.22 g/dL | Standard Error 0.098 |
| Placebo | Total Protein, Albumin | 16 week total protein | 7.8 g/dL | Standard Error 0.2 |
Secondary
Vitals - Blood Pressure
measurement of blood pressure (mmHg)
Time frame: 0 weeks and 16 weeks
Population: We could not analyze all the patients due to adverse events, drop outs or not all participants had data available for all measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL 30 and 50ug/Day | Vitals - Blood Pressure | 0 week BP systolic | 134.85 mm Hg | Standard Error 3.9 |
| APL 30 and 50ug/Day | Vitals - Blood Pressure | 16 week BP systolic | 130.35 mm Hg | Standard Error 4.2 |
| APL 30 and 50ug/Day | Vitals - Blood Pressure | 0 week diastolic | 77.23 mm Hg | Standard Error 2.53 |
| APL 30 and 50ug/Day | Vitals - Blood Pressure | 16 week diastolic | 76.9 mm Hg | Standard Error 2.74 |
| Placebo | Vitals - Blood Pressure | 16 week diastolic | 74.75 mm Hg | Standard Error 3.67 |
| Placebo | Vitals - Blood Pressure | 0 week BP systolic | 131.51 mm Hg | Standard Error 5.2 |
| Placebo | Vitals - Blood Pressure | 0 week diastolic | 71.13 mm Hg | Standard Error 3.4 |
| Placebo | Vitals - Blood Pressure | 16 week BP systolic | 140.67 mm Hg | Standard Error 5.5 |
Secondary
Vital Sign - Pulse
heartbeats per minute
Time frame: 0-16 weeks
Population: We could not analyze all the patients due to adverse events, drop outs or not all participants had data available for all measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL 30 and 50ug/Day | Vital Sign - Pulse | 0 week pulse | 73.8 beats per minute | Standard Error 3.23 |
| APL 30 and 50ug/Day | Vital Sign - Pulse | 16 week pulse | 74.74 beats per minute | Standard Error 3.47 |
| Placebo | Vital Sign - Pulse | 0 week pulse | 72.46 beats per minute | Standard Error 4.34 |
| Placebo | Vital Sign - Pulse | 16 week pulse | 71.83 beats per minute | Standard Error 4.6 |
Secondary
Vital Signs-Temperature
Time frame: 0-16 weeks
Population: We could not analyze all the patients due to adverse events, drop outs or not all participants had data available for all measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL 30 and 50ug/Day | Vital Signs-Temperature | 0 week temperature | 97.4 degrees Fahrenheit | Standard Error 0.19 |
| APL 30 and 50ug/Day | Vital Signs-Temperature | 16 week temperature | 97.4 degrees Fahrenheit | Standard Error 0.2 |
| Placebo | Vital Signs-Temperature | 0 week temperature | 98 degrees Fahrenheit | Standard Error 0.25 |
| Placebo | Vital Signs-Temperature | 16 week temperature | 97.83 degrees Fahrenheit | Standard Error 0.27 |
Secondary
Vitals - Respirations
Respirations represents breaths per minute
Time frame: 0 weeks and 16 weeks
Population: We could not analyze all the patients due to adverse events, drop outs or not all participants had data available for all measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL 30 and 50ug/Day | Vitals - Respirations | 16 weeks | 18.54 breaths per minute | Standard Error 0.4 |
| APL 30 and 50ug/Day | Vitals - Respirations | 0 weeks | 18.3 breaths per minute | Standard Error 0.63 |
| Placebo | Vitals - Respirations | 0 weeks | 18.84 breaths per minute | Standard Error 0.5 |
| Placebo | Vitals - Respirations | 16 weeks | 17.7 breaths per minute | Standard Error 0.5 |
Secondary
Weight
Weight in kg
Time frame: 0-16 weeks
Population: We could not analyze all the patients due to adverse events, drop outs or not all participants had data available for all measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL 30 and 50ug/Day | Weight | 0 week weight | 84.06 kilograms | Standard Error 3.17 |
| APL 30 and 50ug/Day | Weight | 16 week weight | 83 kilograms | Standard Error 3.18 |
| Placebo | Weight | 0 week weight | 93.5 kilograms | Standard Error 4 |
| Placebo | Weight | 16 week weight | 95.21 kilograms | Standard Error 4 |
Secondary
White Blood Count
Laboratory Results of A12 vs Placebo to determine whether APL has any effect on routine blood counts, chemistries, electrolytes, immunoglobulin to measure potential toxicities
Time frame: 0-16 weeks
Population: We could not analyze all the patients due to adverse events, drop outs or not all participants had data available for all measurements
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APL 30 and 50ug/Day | White Blood Count | 0 week WBC | 7.24 10^3 cells/uL | Standard Error 0.43 |
| APL 30 and 50ug/Day | White Blood Count | 16 week WBC | 7.26 10^3 cells/uL | Standard Error 0.47 |
| Placebo | White Blood Count | 0 week WBC | 5.88 10^3 cells/uL | Standard Error 0.57 |
| Placebo | White Blood Count | 16 week WBC | 6.23 10^3 cells/uL | Standard Error 0.61 |