Pulmonary Alveolar Proteinosis (PAP)Phase 1NCT01842386
Rituximab for Anti-cytokine Autoantibody-Associated Diseases
A Phase 1 study testing Rituximab in people with Pulmonary Alveolar Proteinosis (PAP) and Severe Mucocutaneous Candidiasis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
Background: Healthy people have white blood cells that protect them against bacteria, viruses, and fungi. However, some people have diseases which cause the body to make white blood cells that do not work properly. These white blood cells can attack the body s own proteins. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Pulmonary Alveolar Proteinosis (PAP), Severe Mucocutaneous Candidiasis
- What is being tested?
- Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Apr 2014to 6 May 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects (greater than or equal to 18 years of age) are eligible if they meet the following criteria:
- Currently enrolled in one of the following protocols: 95-I-0066, 07-I-0033, 01-I-0202, or 93-I-0119.
- Presence of anticytokine autoantibodies in serum or plasma, along with the anticipated clinical consequences of the identified anticytokine autoantibody including, but not limited to:
- Anti-IFN- >= autoantibodies and disseminated NTM.
- Anti-IL-17 autoantibodies and CMC.
- Anti-GM-CSF autoantibodies and PAP or cryptococcosis.
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- Progression of anticytokine autoantibody-associated diseases despite conventional therapy, including, but not limited to:
- Antimycobacterials for disseminated NTM.
- Antifungals for mucocutaneous candidiasis or cryptococcosis.
- Subcutaneous or inhaled GM-CSF and/or whole lung lavage for PAP.
- For ongoing autoantibody-associated infection, stable, optimized antibiotic regimen for at least 1 month prior to initiation of rituximab and ability to continue these antibiotics throughout treatment with rituximab.
- Willingness to comply with study medication, visits, and procedures, as deemed necessary by the study investigator.
- Willingness to have samples stored for future research and genetic testing.
- Willingness to be hospitalized for the inpatient visits (initial doese on day 1 and day 15 will occur in the inpatient unit.
- Negative serum pregnancy test result for women of childbearing potential.
- Women of childbearing potential and men are eligible if they agree to postpone conception for 18 months following rituximab therapy. They must agree to use 2 adequate methods of contraception, such as:
- Hormonal contraception.
- Male or female condoms with or without a spermicide, diaphragm or cervical cap with a spermicide, or intrauterine device.
- Sterilization of either partner.
Who cannot join
- Subjects who meet the following criteria are not eligible to enter the study:
- HIV seropositivity.
- Active underlying malignancy, except thymoma and basal and squamous cell carcinoma.
- Immunomodulatory or immunosuppressive therapy, including:
- Corticosteroids at a dose equivalent to greater than or equal to 15 mg of prednisone/day at any time during the month immediately prior to enrollment.
- History of using biologic agents or any other systemic immune-suppressive or immunomodulatory agents within the past year.
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- Use of another investigational study agent within 8 weeks of enrollment.
- Known anaphylaxis or IgE-mediated hypersensitivity to murine proteins or any component of the study medication.
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies.
- Evidence of significant uncontrolled concomitant diseases, such as cardiovascular disease, or nervous system, pulmonary, renal, hepatic, endocrine, or gastrointestinal disorders.
- Diagnosis of an unrelated underlying immunodeficiency.
- Hepatitis B (subjects with hepatitis C are eligible to enter the study).
- Live vaccines within 1 month prior to receiving the study drug.
- Unsuitable participation as judged by the principal investigator.
- History of cancer, including solid tumors and hematologic malignancies (except basal cell or squamous cell carcinoma of the skin that have been excised and cured and thymoma).
- History of alcohol, drug, or chemical abuse within 6 months prior to screening.
- Poor peripheral venous access.
- Intolerance or contraindications to oral or IV corticosteroids.
- Screening laboratory values:
- Serum creatinine >1.4 mg/dL for women and >1.6 mg/dL for men.
- Platelet count <100,000/ L.
- Absolute neutrophil count <1500 cells/ L.
- IgG <5.65 times 10(-2) mg/dL or IgM <0.55 times 10(-2) mg/dL.
- Breastfeeding.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Rituximab (Anti-CD20) for the Treatment of Subjects With Anticytokine Autoantibody-Associated Diseases
Background:
- Healthy people have white blood cells that protect them against bacteria, viruses, and fungi. However, some people have diseases which cause the body to make white blood cells that do not work properly. These white blood cells can attack the body s own proteins. These types of diseases are called anti-cytokine autoantibody-associated diseases. They can cause severe illnesses and even death. They are also difficult to treat with standard drugs.
- Rituximab is a drug used to treat rheumatoid arthritis. It attacks white blood cells that do not work properly. Currently, it is not approved for treating anti-cytokine autoantibody-associated diseases. However, researchers think that it may be able to help treat people with these immune diseases.
Read more
Objectives:
- To see if rituximab is a safe and effective treatment for anti-cytokine autoantibody-associated diseases.
Eligibility:
- Individuals at least 18 years of age who have anti-cytokine autoantibody-associated diseases.
- Participants must also be enrolled in a related immune disorder study at the National Institutes of Health.
Design:
- The study will last 24 months. Participants will take rituximab for 6 months and have follow-up visits for the remaining 18 months.
- Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Other samples will be collected as needed if participants currently have an infection.
- Participants will enter the hospital for 1 week at the start of treatment. They will have four doses of rituximab given 2 days apart. This first treatment will be monitored with frequent blood tests.
- Over the next 6 months, participants will have four more doses of rituximab given about 1 month apart. Treatment will be monitored with frequent blood tests and sample collections as needed.
- There will be four follow-up study visits at 3, 6, 12, and 18 months after the last dose of rituximab.
Read the detailed description
Anticytokine autoantibodies are an important and emerging cause of disease. Anticytokine autoantibody-associated diseases include disseminated nontuberculous mycobacterial infection caused by anti-interferon- >= autoantibodies, severe mucocutaneous candidiasis caused by anti-interleukin-17 autoantibodies, and pulmonary alveolar proteinosis caused by anti-granulocyte macrophage colony stimulating factor autoantibodies. Many subjects undergoing treatments related to these diseases fail to respond or develop toxicity to long term therapy. Rituximab, an anti-CD20 monoclonal antibody that targets antibody-producing B cells, has been used successfully to treat autoimmune diseases (e.g., rheumatoid arthritis), as well as syndromes caused by pathogenic anticytokine autoantibodies (e.g., myasthenia gravis and pemphigus vulgaris). This is a phase I, single arm, open-label study evaluating the safety and clinical response to rituximab treatment in subjects (greater than or equal to 18 years of age; n=20) with anticytokine autoantibody-associated diseases who are intolerant or refractory to conventional treatment. Rituximab will be administered as intravenous infusions of 1 gram on days 1 and 15, and subsequently if indicated up to once a month for 5 months (plus or minue 5 days for each visit) starting on approximately day 42. Follow-up visits will occur within 3, 6, 9, 12, 15, and 18 months (plus or minus 2 weeks for each visit) after the last infusion. Subjects will be maintained on a background of appropriate therapy for their respective diseases. The safety and clinical response to rituximab will be assessed by clinical and laboratory parameters while subjects are receiving rituximab, and for an additional year and a half after completion of treatment. Patients may be retreated at the discretion of the Principal Investigator.
- Being tested
- Rituximab
- Keywords
- Pulmonary Alveolar Proteinosis, Autoantibodies, Mucocutaneous Candidiasis, Anti-Granulocyte, Macrophage
- Medical subject headings
- Pulmonary Alveolar Proteinosis, Candidiasis, Chronic Mucocutaneous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
Subjects will receive intravenous (IV) infusions of rituximab 1 gram on days 1 and 15, and subsequently if indicated up to once a month for 5 months (+/-5 days for each visit) starting approximately on day 42. Subjects whose infections respond positively to the treatment but then relapse may be offered additional treatment.
| Study group | Role | What they receive |
|---|---|---|
| Rituximab | Experimental | Adults (=18 years of age) with anticytokine autoantibodyassociated diseases who are refractory to conventional treatment and who test negative for the human immunodeficiency virus (HIV) Receives: Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
safe and tolerable administration of rituximab in subjects with anticytokine autoantibody-associated diseases who are refractory to conventional treatment
safe and tolerable administration of rituximab in subjects with anticytokine autoantibody-associated diseases who are refractory to conventional treatment
Measured: at study end
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2013 (estimated)
- Study start29 Apr 2014
- Primary completion6 May 2021
- Study completion6 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Alveolar Proteinosis (PAP)Studies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Christa S Zerbe, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01842386
- Sponsor's protocol ID
- 130082
- Other IDs
- 13-I-0082
- Status last verified
- 7 Aug 2026
- First submitted
- 25 Apr 2013
- Last updated
- 26 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rituximab (Anti-CD20) for the Treatment of Subjects With Anticytokine Autoantibody-Associated Diseases
- ClinicalTrials.gov ID
- NCT01842386
- Acronym / sponsor ID
- 130082
- Keywords
- Pulmonary Alveolar Proteinosis, Autoantibodies, Mucocutaneous Candidiasis, Anti-Granulocyte, Macrophage
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 29 Apr 2014 (actual)
- Primary completion
- 6 May 2021 (actual)
- Study completion
- 6 May 2021 (actual)
- First posted
- 29 Apr 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Healthy people have white blood cells that protect them against bacteria, viruses, and fungi. However, some people have diseases which cause the body to make white blood cells that do not work properly. These white blood cells can attack the body s own proteins. These types of diseases are called anti-cytokine autoantibody-associated diseases. They can cause severe illnesses and even death. They are also difficult to treat with standard drugs.
- Rituximab is a drug used to treat rheumatoid arthritis. It attacks white blood cells that do not work properly. Currently, it is not approved for treating anti-cytokine autoantibody-associated diseases. However, researchers think that it may be able to help treat people with these immune diseases.
Objectives:
- To see if rituximab is a safe and effective treatment for anti-cytokine autoantibody-associated diseases.
Eligibility:
- Individuals at least 18 years of age who have anti-cytokine autoantibody-associated diseases.
- Participants must also be enrolled in a related immune disorder study at the National Institutes of Health.
Design:
- The study will last 24 months. Participants will take rituximab for 6 months and have follow-up visits for the remaining 18 months.
- Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Other samples will be collected as needed if participants currently have an infection.
- Participants will enter the hospital for 1 week at the start of treatment. They will have four doses of rituximab given 2 days apart. This first treatment will be monitored with frequent blood tests.
- Over the next 6 months, participants will have four more doses of rituximab given about 1 month apart. Treatment will be monitored with frequent blood tests and sample collections as needed.
- There will be four follow-up study visits at 3, 6, 12, and 18 months after the last dose of rituximab.
Detailed description
Anticytokine autoantibodies are an important and emerging cause of disease. Anticytokine autoantibody-associated diseases include disseminated nontuberculous mycobacterial infection caused by anti-interferon- >= autoantibodies, severe mucocutaneous candidiasis caused by anti-interleukin-17 autoantibodies, and pulmonary alveolar proteinosis caused by anti-granulocyte macrophage colony stimulating factor autoantibodies. Many subjects undergoing treatments related to these diseases fail to respond or develop toxicity to long term therapy. Rituximab, an anti-CD20 monoclonal antibody that targets antibody-producing B cells, has been used successfully to treat autoimmune diseases (e.g., rheumatoid arthritis), as well as syndromes caused by pathogenic anticytokine autoantibodies (e.g., myasthenia gravis and pemphigus vulgaris). This is a phase I, single arm, open-label study evaluating the safety and clinical response to rituximab treatment in subjects (greater than or equal to 18 years of age; n=20) with anticytokine autoantibody-associated diseases who are intolerant or refractory to conventional treatment. Rituximab will be administered as intravenous infusions of 1 gram on days 1 and 15, and subsequently if indicated up to once a month for 5 months (plus or minue 5 days for each visit) starting on approximately day 42. Follow-up visits will occur within 3, 6, 9, 12, 15, and 18 months (plus or minus 2 weeks for each visit) after the last infusion. Subjects will be maintained on a background of appropriate therapy for their respective diseases. The safety and clinical response to rituximab will be assessed by clinical and laboratory parameters while subjects are receiving rituximab, and for an additional year and a half after completion of treatment. Patients may be retreated at the discretion of the Principal Investigator.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Rituximab | Experimental | Drug: RituximabAdults (=18 years of age) with anticytokine autoantibodyassociated diseases who are refractory to conventional treatment and who test negative for the human immunodeficiency virus (HIV) |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Subjects (greater than or equal to 18 years of age) are eligible if they meet the following criteria:
- Currently enrolled in one of the following protocols: 95-I-0066, 07-I-0033, 01-I-0202, or 93-I-0119.
- Presence of anticytokine autoantibodies in serum or plasma, along with the anticipated clinical consequences of the identified anticytokine autoantibody including, but not limited to:
- Progression of anticytokine autoantibody-associated diseases despite conventional therapy, including, but not limited to:
- For ongoing autoantibody-associated infection, stable, optimized antibiotic regimen for at least 1 month prior to initiation of rituximab and ability to continue these antibiotics throughout treatment with rituximab.
Key exclusion criteria (24 listed)
- HIV seropositivity.
- Active underlying malignancy, except thymoma and basal and squamous cell carcinoma.
- Immunomodulatory or immunosuppressive therapy, including:
- Use of another investigational study agent within 8 weeks of enrollment.
- Known anaphylaxis or IgE-mediated hypersensitivity to murine proteins or any component of the study medication.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RituximabSubjects will receive intravenous (IV) infusions of rituximab 1 gram on days 1 and 15, and subsequently if indicated up to once a month for 5 months (+/-5 days for each visit) starting approximately on day 42. Subjects whose infections respond positively to the treatment but then relapse may be offered additional treatment. | Drug | Rituximab |
Primary outcome
safe and tolerable administration of rituximab in subjects with anticytokine autoantibody-associated diseases who are refractory to conventional treatment
Time frame: at study end
safe and tolerable administration of rituximab in subjects with anticytokine autoantibody-associated diseases who are refractory to conventional treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christa S Zerbe, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Rituximab in people with Pulmonary Alveolar Proteinosis (PAP) and Severe Mucocutaneous Candidiasis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
safe and tolerable administration of rituximab in subjects with anticytokine autoantibody-associated diseases who are refractory to conventional treatment (time frame: at study end). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2026.