Use of Infliximab for the Treatment of Pemphigus Vulgaris

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00283712
• Collaborator: Autoimmunity Centers of Excellence (Other)
• Enrollment: 20
• Locations: 4
• Arms: 2
• Duration (Months): 60
• Patients Per Site: 5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Pemphigus vulgaris (PV) is a rare skin disorder that causes blistering of the skin and mucous membranes. Infliximab is a man-made antibody used to treat certain types of immune system disorders, including rheumatoid arthritis and Crohn's disease. This study will determine if infliximab given in combination with prednisone is a safe and effective treatment for adults with PV.

Condition or Disease	Intervention/Treatment	Phase
Pemphigus	Drug: Infliximab; Other: Placebo Comparator	Phase 2

Detailed Description

PV involves blistering of the outer layer of skin and mucous membranes, causing a separation of epidermal cells. The disease occurs when the immune system produces antibodies to specific proteins in the skin and mucous membranes; the cause for production of these autoantibodies is unknown. Infliximab is a genetically engineered monoclonal antibody directed against tumor necrosis factor (TNF)-alpha, a chemical messenger that activates an immune response. Infliximab has been used to treat other autoimmune disorders, including rheumatoid arthritis, ankylosing spondylitis, and Crohn's disease. This study will evaluate the safety and efficacy of infliximab given in combination with prednisone for the treatment of adults with PV.

This study will last 26 weeks. At study entry, all patients will be taking a stable dose of prednisone (or an equivalent corticosteroid) of 20 to 120 mg/day for at least 2 weeks prior to study entry. Patients will be randomly assigned to one of two arms: experimental or placebo comparator. The experimental treatment arm will receive infusions of infliximab, and the control arm will receive placebo. Infusions will be given at study entry and Weeks 2, 6, and 14. Before the start of each infusion, a physical exam, vital signs measurement, medical and medication history, review of a disease activity log, a skin evaluation, and blood collection will occur. During each infusion and for 1 hour postinfusion, patients' vital signs will be monitored for any adverse events. Patients will need a responsible adult to take them home after they are discharged from the treatment facility; this person should remain with the patient overnight in case any problems arise from the treatment. The patient will be contacted by phone that night and the next morning after infusion and will be asked about any adverse effects they may have experienced. Those patients that experience adverse effects may be asked to return to the treatment facility for examination. Prednisone doses may be tapered by 15 percent every 2 weeks during the study at the investigator's discretion.

There will be a total of 9 study visits until Week 26: screening, study entry, Week 2, and every 4 weeks thereafter. Each study visit will include a physical exam, vital signs measurement, medical and medication history, a review of the disease activity log and adverse events experienced since the last visit, skin assessments, and blood collection; patients will also be asked to complete a tuberculosis (TB) questionnaire. Patients will be asked to complete quality of life questionnaires at study entry and Weeks 10, 18, and 26. Skin biopsies of unaffected skin will be done at study entry and Weeks 10, 18, and 26; if patients have PV-associated lesions, additional skin biopsies of affected skin will be done at study entry and Week 18.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled Phase II Trial of Infliximab in Subjects With Pemphigus Vulgaris Receiving Prednisone
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: Dec 1, 2010
• Actual Study Completion Date: Mar 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Infliximab Participants are randomized to receive intravenous infusions of infliximab (5mg/kg reconstituted in 10 mL of Sterile Water for Injection, USP ) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a masked (blinded) fashion. Refer to section titled, "Detailed Description" for additional treatment information.	Drug: Infliximab; Chimeric IgG monoclonal antibody that binds to TNF-alpha, generally used to treat Crohn's disease, given in a dosage of 5 mg/kg; Other Names: Remicade®
Placebo Comparator: Placebo Comparator Participants are randomized to receive intravenous infusions of placebo (5 mg/kg comprised of a white lyophilized powder reconstituted in 10 mL of Sterile Water for Injection, USP) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a masked (blinded) fashion. Refer to section titled, "Detailed Description" for additional treatment information.	Other: Placebo Comparator; Placebo administered in place of infliximab for control group; Other Names: Control Arm

Outcome Measures

Primary Outcome Measures

1. Participant Response to Treatment at Week 18 [Baseline to Week 18]

   Participants classified as responders at Week 18 had: 1. Achieved a prednisone dosage <= 25% of the initial starting dose or <= 10 mg/day (whichever is greater), and 2. Had no new blisters within the previous 4 weeks.

2. Treatment-Related Adverse Events >= Grade 3 On or Before Week 18 [Baseline to Week 18]

   Grades were based on the National Cancer Institute (NCI), Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 3.0. An adverse event (AE) was considered treatment-related if it was classified as unlikely, possibly, probably, or definitely related to study treatment. Participants who experienced at least one treatment-related, grade 3 or higher AE were counted only once. AEs of skin including rash, skin ulceration, and chelitis as defined by the NCI-CTCAE V3.0 System Organ Class of "Skin and Subcutaneous Tissues Disorders" were excluded.

Secondary Outcome Measures

1. Participant Response to Treatment at Week 18 [Baseline to Week 18]

   Participants classified as responders at Week 18 had: 1. Achieved a prednisone dosage <= 25% of the initial starting dose or <=10 mg/day (whichever is greater), and 2. Had no new blisters within the previous 4 weeks.

2. Participant Modified Response Status at Week 18 [Baseline to Week 18]

   Modified responder status was defined as participants achieving a prednisone dosage <=25% of the initial starting dose or <=10 mg/day (whichever is greater) at Week 18 regardless of status on new blister formation during the previous 4 weeks.

3. Participant Time to Cessation of New Blisters [Baseline to Week 26]

   Time to cessation of new blisters was defined as the time from a participant's first treatment infusion date to the first date where that date and all subsequent dates had no new blisters. Participant diaries were used to assess new blister formation. To achieve cessation, participants had to be free of new blisters at least 3 weeks prior to their last assessment. In order to analyze missing or incomplete data, the data was censored at the date where a participant had no more data or on the date where 50% of the participant's data was missing past that point.

4. Time to 80% Lesion Healing [Baseline to Week 26]

   Time to 80% healing of existing erosions/ulcerations at time of enrollment was assessed using the SAGE II computerized burn-mapping system. The date of 80% healing of existing erosions/ulcerations at time of enrollment was defined as follows: the first date at which the percent of total body surface area (BSA) involved is at least 80% less than the percent of total BSA calculated at the time of enrollment, where the baseline percent of total BSA must be greater than zero percent. If a participant had missing post-baseline assessments, their data was censored at their last non-missing assessment date.

5. Total Prednisone Dosage Required for Participants to Achieve Cessation of New Blisters [Baseline to Week 26]

   Each participant's prednisone dose was summed from the time of enrollment until the date of cessation of new blisters. Actual prednisone use per day was computed as the average over all days in the week.

6. Total Prednisone Dosage Required for Participants to Achieve 80% Healing of Existing Erosions [Baseline to Week 26]

   Each participant's prednisone dose was summed from the time of enrollment until the date of 80% healing of existing erosions. Actual prednisone use per day was computed as the average over all days in the week.

7. Participant Health Related Quality of Life (Medical Outcome Study Short Form 36) Score Changes From Baseline to Week 18 [Baseline to Week 18]

   The Medical Outcome Study Short Form 36 (MOS SF-36) measures health -related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores: PCS=physical functioning, role-physical, bodily pain, and general health; MCS=vitality, social functioning, role-emotional, and mental health. Scoring is done for both subscores and summary scores. For both, 0=worst score (or quality of life) and 100=best score. Change from baseline is computed as the value at Week 18 minus the baseline value. A positive value in change from Baseline indicates an improvement and a negative value worsening.

8. Participant Dermatology-Related Quality of Life Changes From Baseline to Week 18 [Baseline to Week 18]

   The Dermatology Life Quality Index (DLQI) is a 10-question questionnaire with a weighted value to each question. The DLQI score was calculated by summing the score of each question, resulting in a maximum score of 30 and a minimum score of 0. The higher the score, the greater quality of life is impaired. Change from baseline values (defined as the visit value - baseline value) were calculated. A negative change indicates better quality of life; a positive change indicates poorer quality of life.

9. Participant Duration of Clinical Response [Baseline to Week 26]

   The primary efficacy endpoint of response to treatment at Week 18 was reassessed at study weeks 22 and 26 for participants who were responders at Week 18. Participants classified as responders had: 1. Achieved a prednisone dosage <= 25% of the initial starting dose or <= 10 mg/day (whichever is greater), and 2. had no new blisters within the previous 4 weeks.

10. Participants Who Experienced Severe Infusion Reactions [Baseline to Week 26]

    Participants who experienced severe infusion reactions of Grade 3 or greater based on the National Cancer Institute (NCI), Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 3.0 were assessed.

11. Participants Who Experienced Severe Infectious Complications [Baseline to Week 26]

    Serious and life-threatening infections of Grade 3 or greater based on the National Cancer Institute (NCI), Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 3.0 were assessed.

12. Adverse Events Resulting in Treatment Discontinuation [Baseline to Week 26]

    Adverse events experienced by participants resulting in study treatment discontinuation and assessed by the investigators as at least possibly related to treatment (i.e., possibly, probably, definitely) were assessed.

13. Participant Pemphigus Vulgaris Disease Activity Score [Baseline to Week 26]

    The Pemphigus Vulgaris Disease Activity (PVDA) score was used to grade a participant's disease activity using the SAGE II computerized burn mapping system, which calculated the total body surface area (BSA) involved. Scores were based on the number of new lesions and blisters present, old lesion history and BSA involved. Scores range from 0 to 3 (none to severe disease activity). A new disease activity score of 3 or an old lesion score of 3 indicates active disease. New disease activity scores of 3 for a 1-month duration or an old lesion score of 3 for 2 consecutive months was cause for removal from the study treatment

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Positive direct immunofluorescence of patient's skin showing IgG or complement C3 protein on cell surface with histopathology of lesional skin biopsies consistent with diagnosis of pemphigus vulgaris

• Failure to completely respond to standard steroid therapy (equivalent to prednisone 1 to 2 mg/kg/day followed by tapering)

• Systemic corticosteroid therapy of at least 20 mg prednisone daily and no more than 120 mg/day

• Inability to reduce systemic corticosteroid dosage below 20 mg/day for at least 8 weeks

• Stable dosage of prednisone for at least 2 weeks prior to study entry

• Oral/mucosal disease or skin disease. Detailed information about this criterion can be found in the protocol

• Willing to comply with the study protocol

• Willing to use acceptable means of contraception for the duration of the study and for 6 months after the end of the study

Exclusion Criteria:

• Positive tuberculosis (TB) test within 1 month prior to first administration of study drug

• History of latent or active TB prior to screening

• Signs or symptoms suggestive of TB disease by medical history or physical examination within 3 months prior to first administration of study drug

• Posterior/anterior/lateral chest radiograph within 3 months prior to screening showing evidence of cancer, infection, or abnormalities (apical scarring) suggestive of previous TB

• Serious infection, hospitalization for an infection, or treatment with intravenous (IV) antibiotics for an infection within 2 months prior to screening. Patients who have had less serious infections are eligible for this study at the discretion of the investigator.

• History or presence of opportunistic infections within 6 months prior to screening

• History of receiving human/murine recombinant products

• Known allergy to murine products or other chimeric proteins

• Human immunodeficiency virus (HIV) infected

• Chronic hepatitis B or hepatitis C virus infection

• History of hepatitis C virus infection

• Cancer within the 5 years prior to study entry. Patients with completely resected non-melanoma skin cancers are not excluded.

• History or presence of congestive heart failure

• History or presence of seizure or demyelinating disorder

• History of latent or active granulomatous infection, including TB, histoplasmosis, or coccidioidomycosis

• Received a Bacillus Calmette-Guerin (BCG) vaccine within 12 months of screening

• History of lymphoproliferative disease, including lymphoma or signs and symptoms of possible lymphoproliferative disease, such as lymphadenopathy of unusual size or location or enlarged spleen

• Current signs or symptoms of severe progressive or uncontrolled kidney, liver, blood, gastrointestinal, endocrine, lung, heart, neurologic, or cerebral disease

• Have had chronic or recurrent infectious disease including, but not limited to, chronic kidney infection, chronic chest infection, sinusitis, recurrent urinary tract infection, infected skin wound, or ulcer

• Previous treatment with infliximab, other monoclonal antibodies, or antibody fragments

• Previous treatment with etanercept or other anti-tumor necrosis factor (TNF) agents in the 3 months prior to screening

• Treatment with methotrexate, azathioprine, mycophenolate mofetil, plasmapheresis, IV immunoglobulin, pulse systemic corticosteroids, or other systemic immunosuppressive agents within the 4 weeks prior to study entry

• History of alcohol or drug abuse within the 3 years prior to study entry

• History of noncompliance to medical regimens

• History of a systemic inflammatory disease other than pemphigus vulgaris

• History of a medical condition that would interfere with participation or increase the risk to the participant

• Unable or unwilling to undergo blood draws because of poor tolerability or lack of easy access

• Use of any investigational drug within 30 days prior to screening OR within 5 half-lives of the investigational agent, whichever is longer

• Participation in another investigative clinical trial

• Presence of transplanted solid organ. Participants who have received a corneal transplant more than 3 months prior to screening are not excluded.

• Require certain medications

• Other conditions or circumstances that could interfere with participant's adherence to the study requirements

• Pregnancy, breastfeeding, or plans to become pregnant

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Norris Cancer Center, University of Southern California	Los Angeles	California	United States	90033
2	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
3	Duke University Medical Center	Durham	North Carolina	United States	27710
4	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)
• Autoimmunity Centers of Excellence

Investigators

• Study Chair: Russell P. Hall, MD, Division of Dermatology, Duke University Medical Center
• Study Chair: E. William St. Clair, MD, Division of Rheumatology and Immunology, Duke University Medical Center
• Principal Investigator: Garnett Kelsoe, DSci, Department of Immunology, Duke University
• Principal Investigator: Victoria Werth, MD, Department of Dermatology, University of Pennsylvania School of Medicine
• Principal Investigator: Janet Fairley, MD, Department of Dermatology, University of Iowa
• Principal Investigator: David Woodley, MD, Department of Dermatology, Norris Cancer Center, University of Southern California

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• National Institute of Allergy and Infectious Diseases (NIAID)
• Division of Allergy, Immunology, and Transplantation (DAIT)
• Autoimmunity Centers of Excellence (ACE)

Publications

• Anhalt GJ, Díaz LA. Pemphigus vulgaris--a model for cutaneous autoimmunity. J Am Acad Dermatol. 2004 Jul;51(1 Suppl):S20-1. Review.
• Drosou A, Kirsner RS, Welsh E, Sullivan TP, Kerdel FA. Use of infliximab, an anti-tumor necrosis alpha antibody, for inflammatory dermatoses. J Cutan Med Surg. 2003 Sep-Oct;7(5):382-6. Epub 2003 Sep 24.
• Jacobi A, Shuler G, Hertl M. Rapid control of therapy-refractory pemphigus vulgaris by treatment with the tumour necrosis factor-alpha inhibitor infliximab. Br J Dermatol. 2005 Aug;153(2):448-9.
• Pardo J, Mercader P, Mahiques L, Sanchez-Carazo JL, Oliver V, Fortea JM. Infliximab in the management of severe pemphigus vulgaris. Br J Dermatol. 2005 Jul;153(1):222-3.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT00283712
• Other Study ID Numbers: DAIT APV01
• First Posted: Jan 30, 2006
• Last Update Posted: Dec 6, 2017
• Last Verified: Nov 1, 2017

• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): Skin Diseases; Autoimmune Diseases
• Additional relevant MeSH terms: Pemphigus; Infliximab

Study Results

Participant Flow

Recruitment Details	Four study centers in the United States enrolled 20 subjects with pemphigus vulgaris (PV) who met entry criteria between August 2005 and December 2010.
Pre-assignment Detail	Each participant signed an informed consent before undergoing any screening procedures to assess eligibility. Refer to the Eligibility Section for further details.

Arm/Group Title	Experimental: Infliximab (Remicade, Revellex)	Placebo Comparator: Placebo
Arm/Group Description	Participants were randomized to receive intravenous infusions of infliximab (5mg/kg reconstituted in 10 mL of Sterile Water for Injection, USP ) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a blinded (masked) fashion. Refer to section titled, "Detailed Description" for additional treatment information.	Participants were randomized to receive intravenous infusions of placebo (5 mg/kg comprised of a white lyophilized powder reconstituted in 10 mL of Sterile Water for Injection, USP) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a blinded (masked) fashion. Refer to section titled, "Detailed Description" for additional treatment information.
Period Title: Overall Study
STARTED	10	10
Intent-to-treat Sample	10	10
Safety Sample	10	10
Per-Protocol Sample	6	7
COMPLETED	10	9
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Experimental: Infliximab (Remicade, Revellex)	Placebo Comparator: Placebo	Total
Arm/Group Description	Participants were randomized to receive intravenous infusions of infliximab (5mg/kg reconstituted in 10 mL of Sterile Water for Injection, USP ) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a blinded (masked) fashion. Refer to section titled, "Detailed Description" for additional treatment information.	Participants were randomized to receive intravenous infusions of placebo (5 mg/kg comprised of a white lyophilized powder reconstituted in 10 mL of Sterile Water for Injection, USP) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a blinded (masked) fashion. Refer to section titled, "Detailed Description" for additional treatment information.	Total of all reporting groups
Overall Participants	10	10	20
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	10 100%	8 80%	18 90%
>=65 years	0 0%	2 20%	2 10%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.3 (15.2)	51.1 (13.9)	49.2 (14.3)
Sex: Female, Male (Count of Participants)
Female	4 40%	4 40%	8 40%
Male	6 60%	6 60%	12 60%
Region of Enrollment (participants) [Number]
United States	10 100%	10 100%	20 100%
PDAI Index Total Score (Total Activity Score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Total Activity Score]	23.0 (14.6)	20.8 (10.7)	21.9 (12.4)
Pemphigus Vulgaris Disease Activity Score: Mucosal (Number) [Number]
No oral ulcers	1 10%	2 20%	3 15%
1 to 5 lesions, small ulcers	6 60%	2 20%	8 40%
6 to 10 lesions, small ulcers	2 20%	5 50%	7 35%
>10 lesions or extension erosions	1 10%	1 10%	2 10%
Pemphigus Vulgaris Disease Activity Score: Cutaneous (Number) [Number]
No blisters or erosions	3 30%	3 30%	6 30%
<20 blisters or <1 to 3% BSA	2 20%	4 40%	6 30%
20 to 40 blisters or 3 to 10% BSA	4 40%	2 20%	6 30%
>40 blisters or >10% BSA	1 10%	1 10%	2 10%
Pemphigus Vulgaris Disease Activity Score: Other Organ System (Number) [Number]
No eye, esophageal, laryngeal involvement	9 90%	10 100%	19 95%
Any eye, esophageal, laryngeal involvement	1 10%	0 0%	1 5%

Outcome Measures

1. Primary Outcome

Title	Participant Response to Treatment at Week 18
Description	Participants classified as responders at Week 18 had: 1. Achieved a prednisone dosage <= 25% of the initial starting dose or <= 10 mg/day (whichever is greater), and 2. Had no new blisters within the previous 4 weeks.
Time Frame	Baseline to Week 18

Outcome Measure Data

Analysis Population Description

Intent-to-Treat

Arm/Group Title	Experimental: Infliximab (Remicade, Revellex)	Placebo Comparator: Placebo
Arm/Group Description	Participants were randomized to receive intravenous infusions of infliximab (5mg/kg reconstituted in 10 mL of Sterile Water for Injection, USP ) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a blinded (masked) fashion. Refer to section titled, "Detailed Description" for additional treatment information.	Participants were randomized to receive intravenous infusions of placebo (5 mg/kg comprised of a white lyophilized powder reconstituted in 10 mL of Sterile Water for Injection, USP) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a blinded (masked) fashion. Refer to section titled, "Detailed Description" for additional treatment information.
Measure Participants	10	10
Number [Participants]	1 10%	1 10%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental: Infliximab (Remicade, Revellex), Placebo Comparator: Placebo
	Comments	The study goals were to gather evidence of safety and possible efficacy of infliximab for treatment of pemphigus vulgaris (PV). The analyses focused on estimation rather than hypothesis testing; therefore, there was not sufficient power to detect plausible treatment differences unless they were very large. The sample size reflects a balance between the desire to meet study goals and to expose as few participants as possible until the safety of infliximab for treatment of PV has been clarified.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.00
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.00
	Confidence Interval	(2-Sided) 90%; -0.22 to 0.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Experimental: Infliximab (Remicade, Revellex), Placebo Comparator: Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.00
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 90%; 0.02 to 42.67
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Treatment-Related Adverse Events >= Grade 3 On or Before Week 18
Description	Grades were based on the National Cancer Institute (NCI), Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 3.0. An adverse event (AE) was considered treatment-related if it was classified as unlikely, possibly, probably, or definitely related to study treatment. Participants who experienced at least one treatment-related, grade 3 or higher AE were counted only once. AEs of skin including rash, skin ulceration, and chelitis as defined by the NCI-CTCAE V3.0 System Organ Class of "Skin and Subcutaneous Tissues Disorders" were excluded.
Time Frame	Baseline to Week 18

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Experimental: Infliximab (Remicade, Revellex)	Placebo Comparator: Placebo
Arm/Group Description	Participants were randomized to receive intravenous infusions of infliximab (5mg/kg reconstituted in 10 mL of Sterile Water for Injection, USP ) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a blinded (masked) fashion. Refer to section titled, "Detailed Description" for additional treatment information.	Participants were randomized to receive intravenous infusions of placebo (5 mg/kg comprised of a white lyophilized powder reconstituted in 10 mL of Sterile Water for Injection, USP) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a blinded (masked) fashion. Refer to section titled, "Detailed Description" for additional treatment information.
Measure Participants	10	10
Number [Participants]	0 0%	10 100%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental: Infliximab (Remicade, Revellex), Placebo Comparator: Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.10
	Confidence Interval	(2-Sided) 90%; -0.26 to 0.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Participant Response to Treatment at Week 18
Description	Participants classified as responders at Week 18 had: 1. Achieved a prednisone dosage <= 25% of the initial starting dose or <=10 mg/day (whichever is greater), and 2. Had no new blisters within the previous 4 weeks.
Time Frame	Baseline to Week 18

Outcome Measure Data

Analysis Population Description

Per-protocol

Arm/Group Title	Experimental: Infliximab (Remicade, Revellex)	Placebo Comparator: Placebo
Arm/Group Description	Participants were randomized to receive intravenous infusions of infliximab (5mg/kg reconstituted in 10 mL of Sterile Water for Injection, USP ) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a blinded (masked) fashion. Refer to section titled, "Detailed Description" for additional treatment information.	Participants were randomized to receive intravenous infusions of placebo (5 mg/kg comprised of a white lyophilized powder reconstituted in 10 mL of Sterile Water for Injection, USP) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a blinded (masked) fashion. Refer to section titled, "Detailed Description" for additional treatment information.
Measure Participants	6	7
Number [Participants]	1 10%	1 10%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental: Infliximab (Remicade, Revellex), Placebo Comparator: Placebo
	Comments	The primary endpoint analysis was replicated using the per-protocol population.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.00
	Comments	All secondary analyses are considered supplemental supportive analyses
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.02
	Confidence Interval	(2-Sided) 90%; -0.31 to 0.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Experimental: Infliximab (Remicade, Revellex), Placebo Comparator: Placebo
	Comments	The primary endpoint analysis was replicated using the per-protocol population.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.00
	Comments	All secondary analyses are considered supplemental supportive analyses
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.83
	Confidence Interval	(2-Sided) 90%; 0.02 to 38.35
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Participant Modified Response Status at Week 18
Description	Modified responder status was defined as participants achieving a prednisone dosage <=25% of the initial starting dose or <=10 mg/day (whichever is greater) at Week 18 regardless of status on new blister formation during the previous 4 weeks.
Time Frame	Baseline to Week 18

Outcome Measure Data

Analysis Population Description

Intent-to-Treat

Arm/Group Title	Experimental: Infliximab (Remicade, Revellex)	Placebo Comparator: Placebo
Arm/Group Description	Participants were randomized to receive intravenous infusions of infliximab (5mg/kg reconstituted in 10 mL of Sterile Water for Injection, USP ) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a blinded (masked) fashion. Refer to section titled, "Detailed Description" for additional treatment information.	Participants were randomized to receive intravenous infusions of placebo (5 mg/kg comprised of a white lyophilized powder reconstituted in 10 mL of Sterile Water for Injection, USP) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a blinded (masked) fashion. Refer to section titled, "Detailed Description" for additional treatment information.
Measure Participants	10	10
Number [Participants]	5 50%	3 30%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental: Infliximab (Remicade, Revellex), Placebo Comparator: Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.65
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.20
	Confidence Interval	(2-Sided) 90%; -0.15 to 0.55
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Experimental: Infliximab (Remicade, Revellex), Placebo Comparator: Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.650
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.43
	Confidence Interval	(2-Sided) 90%; 0.06 to 2.79
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Participant Time to Cessation of New Blisters
Description	Time to cessation of new blisters was defined as the time from a participant's first treatment infusion date to the first date where that date and all subsequent dates had no new blisters. Participant diaries were used to assess new blister formation. To achieve cessation, participants had to be free of new blisters at least 3 weeks prior to their last assessment. In order to analyze missing or incomplete data, the data was censored at the date where a participant had no more data or on the date where 50% of the participant's data was missing past that point.
Time Frame	Baseline to Week 26

Outcome Measure Data

Analysis Population Description

Subset of Intent-to-Treat Who Experienced Cessation

Arm/Group Title	Experimental: Infliximab (Remicade, Revellex)	Placebo Comparator: Placebo
Arm/Group Description	Participants were randomized to receive intravenous infusions of infliximab (5mg/kg reconstituted in 10 mL of Sterile Water for Injection, USP ) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a blinded (masked) fashion. Refer to section titled, "Detailed Description" for additional treatment information.	Participants were randomized to receive intravenous infusions of placebo (5 mg/kg comprised of a white lyophilized powder reconstituted in 10 mL of Sterile Water for Injection, USP) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a blinded (masked) fashion. Refer to section titled, "Detailed Description" for additional treatment information.
Measure Participants	5	3
Mean (Standard Deviation) [Days]	133.0 (31.7)	98.0 (49.5)

6. Secondary Outcome

Title	Time to 80% Lesion Healing
Description	Time to 80% healing of existing erosions/ulcerations at time of enrollment was assessed using the SAGE II computerized burn-mapping system. The date of 80% healing of existing erosions/ulcerations at time of enrollment was defined as follows: the first date at which the percent of total body surface area (BSA) involved is at least 80% less than the percent of total BSA calculated at the time of enrollment, where the baseline percent of total BSA must be greater than zero percent. If a participant had missing post-baseline assessments, their data was censored at their last non-missing assessment date.
Time Frame	Baseline to Week 26

Outcome Measure Data

Analysis Population Description

Subset of Intent-to-Treat Who Experienced Lesion Healing

Arm/Group Title	Experimental: Infliximab (Remicade, Revellex)	Placebo Comparator: Placebo
Arm/Group Description	Participants were randomized to receive intravenous infusions of infliximab (5mg/kg reconstituted in 10 mL of Sterile Water for Injection, USP ) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a blinded (masked) fashion. Refer to section titled, "Detailed Description" for additional treatment information.	Participants were randomized to receive intravenous infusions of placebo (5 mg/kg comprised of a white lyophilized powder reconstituted in 10 mL of Sterile Water for Injection, USP) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a blinded (masked) fashion. Refer to section titled, "Detailed Description" for additional treatment information.
Measure Participants	5	4
Mean (Standard Deviation) [Days]	77.8 (74.4)	58.0 (36.0)

7. Secondary Outcome

Title	Total Prednisone Dosage Required for Participants to Achieve Cessation of New Blisters
Description	Each participant's prednisone dose was summed from the time of enrollment until the date of cessation of new blisters. Actual prednisone use per day was computed as the average over all days in the week.
Time Frame	Baseline to Week 26

Outcome Measure Data

Analysis Population Description

Subset of Intent-to-Treat Who Experienced Lesion Cessation

Arm/Group Title	Experimental: Infliximab (Remicade, Revellex)	Placebo Comparator: Placebo
Arm/Group Description	Participants were randomized to receive intravenous infusions of infliximab (5mg/kg reconstituted in 10 mL of Sterile Water for Injection, USP ) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a blinded (masked) fashion. Refer to section titled, "Detailed Description" for additional treatment information.	Participants were randomized to receive intravenous infusions of placebo (5 mg/kg comprised of a white lyophilized powder reconstituted in 10 mL of Sterile Water for Injection, USP) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a blinded (masked) fashion. Refer to section titled, "Detailed Description" for additional treatment information.
Measure Participants	5	3
Mean (Standard Deviation) [mg]	4009.0 (2351.2)	6446.7 (4225.1)

8. Secondary Outcome

Title	Total Prednisone Dosage Required for Participants to Achieve 80% Healing of Existing Erosions
Description	Each participant's prednisone dose was summed from the time of enrollment until the date of 80% healing of existing erosions. Actual prednisone use per day was computed as the average over all days in the week.
Time Frame	Baseline to Week 26

Outcome Measure Data

Analysis Population Description

Subset of Intent-to-Treat Who Experienced Erosion Healing

Arm/Group Title	Experimental: Infliximab (Remicade, Revellex)	Placebo Comparator: Placebo
Arm/Group Description	Participants were randomized to receive intravenous infusions of infliximab (5mg/kg reconstituted in 10 mL of Sterile Water for Injection, USP ) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a blinded (masked) fashion. Refer to section titled, "Detailed Description" for additional treatment information.	Participants were randomized to receive intravenous infusions of placebo (5 mg/kg comprised of a white lyophilized powder reconstituted in 10 mL of Sterile Water for Injection, USP) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a blinded (masked) fashion. Refer to section titled, "Detailed Description" for additional treatment information.
Measure Participants	5	4
Mean (Standard Deviation) [mg]	2921.5 (2978.2)	2958.8 (3223.4)

9. Secondary Outcome

Title	Participant Health Related Quality of Life (Medical Outcome Study Short Form 36) Score Changes From Baseline to Week 18
Description	The Medical Outcome Study Short Form 36 (MOS SF-36) measures health -related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores: PCS=physical functioning, role-physical, bodily pain, and general health; MCS=vitality, social functioning, role-emotional, and mental health. Scoring is done for both subscores and summary scores. For both, 0=worst score (or quality of life) and 100=best score. Change from baseline is computed as the value at Week 18 minus the baseline value. A positive value in change from Baseline indicates an improvement and a negative value worsening.
Time Frame	Baseline to Week 18

Outcome Measure Data

Analysis Population Description

Intent-to-Treat with available data

Arm/Group Title	Experimental: Infliximab (Remicade, Revellex)	Placebo Comparator: Placebo
Arm/Group Description	Participants were randomized to receive intravenous infusions of infliximab (5mg/kg reconstituted in 10 mL of Sterile Water for Injection, USP ) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a blinded (masked) fashion. Refer to section titled, "Detailed Description" for additional treatment information.	Participants were randomized to receive intravenous infusions of placebo (5 mg/kg comprised of a white lyophilized powder reconstituted in 10 mL of Sterile Water for Injection, USP) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a blinded (masked) fashion. Refer to section titled, "Detailed Description" for additional treatment information.
Measure Participants	10	9
Physical Functioning Scale	4.0 (12.1)	4.0 (7.2)
Role Functioning Scale	0.3 (14.2)	6.3 (10.7)
Bodily Pain Scale	3.7 (14.8)	3.2 (12.1)
General Health Scale	-0.8 (7.1)	3.6 (5.8)
Physical Component Scale	2.2 (8.8)	3.5 (7.3)
Vitality Scale	-1.6 (8.1)	1.7 (10.1)
Social Functioning Scale	0.0 (11.5)	3.0 (13.7)
Role Emotional Scale	1.2 (21.5)	4.8 (13.3)
Mental Health Scale	1.4 (6.5)	6.6 (10.4)
Mental Component Scale	-0.5 (9.6)	4.4 (13.3)

10. Secondary Outcome

Title	Participant Dermatology-Related Quality of Life Changes From Baseline to Week 18
Description	The Dermatology Life Quality Index (DLQI) is a 10-question questionnaire with a weighted value to each question. The DLQI score was calculated by summing the score of each question, resulting in a maximum score of 30 and a minimum score of 0. The higher the score, the greater quality of life is impaired. Change from baseline values (defined as the visit value - baseline value) were calculated. A negative change indicates better quality of life; a positive change indicates poorer quality of life.
Time Frame	Baseline to Week 18

Outcome Measure Data

Analysis Population Description

Intent-to-Treat with available data

Arm/Group Title	Experimental: Infliximab (Remicade, Revellex)	Placebo Comparator: Placebo
Arm/Group Description	Participants were randomized to receive intravenous infusions of infliximab (5mg/kg reconstituted in 10 mL of Sterile Water for Injection, USP ) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a blinded (masked) fashion. Refer to section titled, "Detailed Description" for additional treatment information.	Participants were randomized to receive intravenous infusions of placebo (5 mg/kg comprised of a white lyophilized powder reconstituted in 10 mL of Sterile Water for Injection, USP) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a blinded (masked) fashion. Refer to section titled, "Detailed Description" for additional treatment information.
Measure Participants	10	9
Mean (Standard Deviation) [units on a scale]	-2.0 (3.1)	-4.0 (10.8)

11. Secondary Outcome

Title	Participant Duration of Clinical Response
Description	The primary efficacy endpoint of response to treatment at Week 18 was reassessed at study weeks 22 and 26 for participants who were responders at Week 18. Participants classified as responders had: 1. Achieved a prednisone dosage <= 25% of the initial starting dose or <= 10 mg/day (whichever is greater), and 2. had no new blisters within the previous 4 weeks.
Time Frame	Baseline to Week 26

Outcome Measure Data

Analysis Population Description

Participants in the Intent-to-Treat Population Who Were Responders at Week 18

Arm/Group Title	Experimental: Infliximab (Remicade, Revellex)	Placebo Comparator: Placebo
Arm/Group Description	Participants were randomized to receive intravenous infusions of infliximab (5mg/kg reconstituted in 10 mL of Sterile Water for Injection, USP ) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a blinded (masked) fashion. Refer to section titled, "Detailed Description" for additional treatment information.	Participants were randomized to receive intravenous infusions of placebo (5 mg/kg comprised of a white lyophilized powder reconstituted in 10 mL of Sterile Water for Injection, USP) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a blinded (masked) fashion. Refer to section titled, "Detailed Description" for additional treatment information.
Measure Participants	1	1
Week 22	1 10%	0 0%
Week 26	1 10%	0 0%

12. Secondary Outcome

Title	Participants Who Experienced Severe Infusion Reactions
Description	Participants who experienced severe infusion reactions of Grade 3 or greater based on the National Cancer Institute (NCI), Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 3.0 were assessed.
Time Frame	Baseline to Week 26

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Experimental: Infliximab (Remicade, Revellex)	Placebo Comparator: Placebo
Arm/Group Description	Participants were randomized to receive intravenous infusions of infliximab (5mg/kg reconstituted in 10 mL of Sterile Water for Injection, USP ) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a blinded (masked) fashion. Refer to section titled, "Detailed Description" for additional treatment information.	Participants were randomized to receive intravenous infusions of placebo (5 mg/kg comprised of a white lyophilized powder reconstituted in 10 mL of Sterile Water for Injection, USP) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a blinded (masked) fashion. Refer to section titled, "Detailed Description" for additional treatment information.
Measure Participants	10	10
Number [Participants]	0 0%	0 0%

13. Secondary Outcome

Title	Participants Who Experienced Severe Infectious Complications
Description	Serious and life-threatening infections of Grade 3 or greater based on the National Cancer Institute (NCI), Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 3.0 were assessed.
Time Frame	Baseline to Week 26

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Experimental: Infliximab (Remicade, Revellex)	Placebo Comparator: Placebo
Arm/Group Description	Participants were randomized to receive intravenous infusions of infliximab (5mg/kg reconstituted in 10 mL of Sterile Water for Injection, USP ) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a blinded (masked) fashion. Refer to section titled, "Detailed Description" for additional treatment information.	Participants were randomized to receive intravenous infusions of placebo (5 mg/kg comprised of a white lyophilized powder reconstituted in 10 mL of Sterile Water for Injection, USP) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a blinded (masked) fashion. Refer to section titled, "Detailed Description" for additional treatment information.
Measure Participants	10	10
Number [Participants]	0 0%	0 0%

14. Secondary Outcome

Title	Adverse Events Resulting in Treatment Discontinuation
Description	Adverse events experienced by participants resulting in study treatment discontinuation and assessed by the investigators as at least possibly related to treatment (i.e., possibly, probably, definitely) were assessed.
Time Frame	Baseline to Week 26

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Experimental: Infliximab (Remicade, Revellex)	Placebo Comparator: Placebo
Arm/Group Description	Participants were randomized to receive intravenous infusions of infliximab (5mg/kg reconstituted in 10 mL of Sterile Water for Injection, USP ) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a blinded (masked) fashion. Refer to section titled, "Detailed Description" for additional treatment information.	Participants were randomized to receive intravenous infusions of placebo (5 mg/kg comprised of a white lyophilized powder reconstituted in 10 mL of Sterile Water for Injection, USP) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a blinded (masked) fashion. Refer to section titled, "Detailed Description" for additional treatment information.
Measure Participants	10	10
Number [Participants]	2 20%	2 20%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental: Infliximab (Remicade, Revellex), Placebo Comparator: Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.00
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.00
	Confidence Interval	(2-Sided) 90%; -0.3 to 0.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

Title	Participant Pemphigus Vulgaris Disease Activity Score
Description	The Pemphigus Vulgaris Disease Activity (PVDA) score was used to grade a participant's disease activity using the SAGE II computerized burn mapping system, which calculated the total body surface area (BSA) involved. Scores were based on the number of new lesions and blisters present, old lesion history and BSA involved. Scores range from 0 to 3 (none to severe disease activity). A new disease activity score of 3 or an old lesion score of 3 indicates active disease. New disease activity scores of 3 for a 1-month duration or an old lesion score of 3 for 2 consecutive months was cause for removal from the study treatment
Time Frame	Baseline to Week 26

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Experimental: Infliximab (Remicade, Revellex)	Placebo Comparator: Placebo
Arm/Group Description	Participants were randomized to receive intravenous infusions of infliximab (5mg/kg reconstituted in 10 mL of Sterile Water for Injection, USP ) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a blinded (masked) fashion. Refer to section titled, "Detailed Description" for additional treatment information.	Participants were randomized to receive intravenous infusions of placebo (5 mg/kg comprised of a white lyophilized powder reconstituted in 10 mL of Sterile Water for Injection, USP) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a blinded (masked) fashion. Refer to section titled, "Detailed Description" for additional treatment information.
Measure Participants	10	10
New Scores of 3 for a 1- Month Duration	0 0%	0 0%
Old Lesion Scores of 3 in 2 Consecutive Mos.	0 0%	0 0%

Adverse Events

Adverse Event Reporting Description	All Adverse Events are included due to low sample size (20 participants).
Arm/Group Title	Infliximab		Placebo
Arm/Group Description	Subjects randomized to the Infliximab group		Subjects randomized to the Placebo group
All Cause Mortality
	Infliximab		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Infliximab		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/10 (10%)		2/10 (20%)
Blood and lymphatic system disorders
Lymphopenia	0/10 (0%)	0	1/10 (10%)	1
Nervous system disorders
Syncope	0/10 (0%)	0	1/10 (10%)	1
Respiratory, thoracic and mediastinal disorders
Laryngeal obstruction	0/10 (0%)	0	1/10 (10%)	1
Pulmonary embolism	0/10 (0%)	0	1/10 (10%)	1
Skin and subcutaneous tissue disorders
Pemphigus	0/10 (0%)	0	1/10 (10%)	1
Skin ulcer	1/10 (10%)	1	0/10 (0%)	0
Other (Not Including Serious) Adverse Events
	Infliximab		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/10 (90%)		10/10 (100%)
Blood and lymphatic system disorders
Anaemia	1/10 (10%)	1	0/10 (0%)	0
Eosinophilia	1/10 (10%)	1	0/10 (0%)	0
Lymphopenia	1/10 (10%)	1	0/10 (0%)	0
Cardiac disorders
Bradycardia	1/10 (10%)	1	0/10 (0%)	0
Tachycardia	0/10 (0%)	0	1/10 (10%)	1
Ear and labyrinth disorders
Vertigo	1/10 (10%)	1	0/10 (0%)	0
Eye disorders
Blepharitis	1/10 (10%)	1	0/10 (0%)	0
Conjunctival haemorrhage	0/10 (0%)	0	1/10 (10%)	2
Gastrointestinal disorders
Abdominal distension	0/10 (0%)	0	1/10 (10%)	1
Constipation	0/10 (0%)	0	1/10 (10%)	1
Diarrhoea	1/10 (10%)	1	1/10 (10%)	1
Dyspepsia	1/10 (10%)	1	0/10 (0%)	0
Haemorrhoids	1/10 (10%)	1	1/10 (10%)	1
Nausea	2/10 (20%)	2	2/10 (20%)	2
Vomiting	0/10 (0%)	0	2/10 (20%)	3
General disorders
Fatigue	3/10 (30%)	3	4/10 (40%)	5
Feeling hot	0/10 (0%)	0	1/10 (10%)	1
Oedema peripheral	0/10 (0%)	0	1/10 (10%)	1
Pitting oedema	1/10 (10%)	1	0/10 (0%)	0
Pyrexia	0/10 (0%)	0	2/10 (20%)	2
Hepatobiliary disorders
Cholelithiasis	0/10 (0%)	0	1/10 (10%)	1
Infections and infestations
Bronchitis	1/10 (10%)	1	0/10 (0%)	0
Candidiasis	1/10 (10%)	3	1/10 (10%)	1
Folliculitis	1/10 (10%)	1	1/10 (10%)	1
Fungal skin infection	0/10 (0%)	0	1/10 (10%)	1
Gastroenteritis viral	0/10 (0%)	0	1/10 (10%)	1
Influenza	0/10 (0%)	0	1/10 (10%)	1
Nasopharyngitis	1/10 (10%)	2	0/10 (0%)	0
Oral candidiasis	1/10 (10%)	1	1/10 (10%)	1
Oral herpes	1/10 (10%)	1	0/10 (0%)	0
Pharyngitis	0/10 (0%)	0	1/10 (10%)	2
Pneumonia	0/10 (0%)	0	1/10 (10%)	1
Pseudomonas infection	0/10 (0%)	0	1/10 (10%)	1
Rhinitis	1/10 (10%)	2	0/10 (0%)	0
Sinusitis	1/10 (10%)	1	0/10 (0%)	0
Staphylococcal skin infection	1/10 (10%)	2	0/10 (0%)	0
Tinea pedis	1/10 (10%)	1	0/10 (0%)	0
Upper respiratory tract infection	1/10 (10%)	1	1/10 (10%)	2
Vulval abscess	0/10 (0%)	0	1/10 (10%)	1
Vulvovaginal mycotic infection	0/10 (0%)	0	1/10 (10%)	1
Injury, poisoning and procedural complications
Arthropod bite	1/10 (10%)	1	0/10 (0%)	0
Back injury	1/10 (10%)	1	0/10 (0%)	0
Contusion	1/10 (10%)	1	1/10 (10%)	1
Excoriation	1/10 (10%)	1	0/10 (0%)	0
Limb injury	0/10 (0%)	0	2/10 (20%)	2
Sunburn	1/10 (10%)	1	0/10 (0%)	0
Investigations
Alanine aminotransferase increased	2/10 (20%)	2	2/10 (20%)	2
Aspartate aminotransferase increased	1/10 (10%)	1	1/10 (10%)	1
Haemoglobin decreased	0/10 (0%)	0	2/10 (20%)	2
Monocyte count increased	2/10 (20%)	2	0/10 (0%)	0
Neutrophil count increased	2/10 (20%)	2	0/10 (0%)	0
Platelet count decreased	1/10 (10%)	1	0/10 (0%)	0
Transaminases increased	1/10 (10%)	1	0/10 (0%)	0
Metabolism and nutrition disorders
Gout	0/10 (0%)	0	1/10 (10%)	1
Hyperglycaemia	0/10 (0%)	0	1/10 (10%)	1
Hypoalbuminaemia	0/10 (0%)	0	1/10 (10%)	1
Hypoglycaemia	0/10 (0%)	0	1/10 (10%)	1
Hypokalaemia	0/10 (0%)	0	2/10 (20%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	0/10 (0%)	0	1/10 (10%)	1
Arthritis	0/10 (0%)	0	1/10 (10%)	1
Metatarsalgia	1/10 (10%)	1	0/10 (0%)	0
Neck pain	0/10 (0%)	0	1/10 (10%)	1
Pain in extremity	2/10 (20%)	5	0/10 (0%)	0
Tendonitis	1/10 (10%)	1	0/10 (0%)	0
Nervous system disorders
Convulsion	0/10 (0%)	0	1/10 (10%)	1
Dizziness	2/10 (20%)	2	0/10 (0%)	0
Headache	2/10 (20%)	4	1/10 (10%)	3
Migraine	2/10 (20%)	6	0/10 (0%)	0
Psychiatric disorders
Anxiety	0/10 (0%)	0	2/10 (20%)	2
Hallucination, olfactory	1/10 (10%)	1	0/10 (0%)	0
Insomnia	0/10 (0%)	0	1/10 (10%)	1
Reproductive system and breast disorders
Vulvovaginal dryness	1/10 (10%)	1	0/10 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	0/10 (0%)	0	1/10 (10%)	1
Dyspnoea	1/10 (10%)	1	0/10 (0%)	0
Epistaxis	1/10 (10%)	1	1/10 (10%)	3
Rhinitis allergic	0/10 (0%)	0	1/10 (10%)	1
Throat irritation	0/10 (0%)	0	1/10 (10%)	1
Skin and subcutaneous tissue disorders
Alopecia	0/10 (0%)	0	1/10 (10%)	1
Decubitus ulcer	0/10 (0%)	0	1/10 (10%)	1
Dermatitis bullous	1/10 (10%)	1	1/10 (10%)	1
Eczema	0/10 (0%)	0	1/10 (10%)	1
Exfoliative rash	1/10 (10%)	1	1/10 (10%)	1
Heat rash	1/10 (10%)	1	0/10 (0%)	0
Night sweats	1/10 (10%)	1	0/10 (0%)	0
Pemphigus	2/10 (20%)	3	2/10 (20%)	2
Petechiae	1/10 (10%)	1	0/10 (0%)	0
Photosensitivity reaction	0/10 (0%)	0	1/10 (10%)	1
Pruritus	1/10 (10%)	1	0/10 (0%)	0
Rash	1/10 (10%)	2	0/10 (0%)	0
Skin erosion	1/10 (10%)	1	1/10 (10%)	1
Vascular disorders
Flushing	1/10 (10%)	1	0/10 (0%)	0
Hypertension	0/10 (0%)	0	1/10 (10%)	1
Hypotension	1/10 (10%)	2	0/10 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.