VacciniaPhase 2NCT00081835
Evaluation and Treatment of Eye Complications of Vaccinia Vaccination
A Phase 2 study testing NP-016 Vaccine Immune Globulin (IV-VIG) in people with Vaccinia, run by National Eye Institute (NEI) at 1 site in United States.
Trial summary
This study will evaluate patients with eye complications related to vaccination against smallpox to learn more about these conditions. Vaccinia vaccination has been used for more than 100 years for preventing smallpox. Read more about this study
- Who is it for?
- Ages 1 year and older
- Conditions the study is for
- Vaccinia
- What is being tested?
- NP-016 Vaccine Immune Globulin (IV-VIG)
- Type of treatment
- Vaccines, Injection or infusion
- How many people
- 400 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Apr 2004to 15 Aug 2007
- Phase
- Phase 2
- 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 1 year and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- To be eligible to enroll in this study, a prospective participant must satisfy all of the following inclusion criteria:
- The participant, or their parent or guardian if younger than 18 years at enrollment, is able to understand and sign an approved consent form. Any minor participant with adequate reading and writing skills must also sign an assent using a form approved by the local Institutional Review Board or Independent Ethics Committee (IRB/IEC). Minors with verbal skills but without adequate reading and writing skills should have an acknowledgement signed by their parent or guardian to certify that verbal assent to participate was obtained.
- The participant must have received the vaccinia vaccination, been exposed to a person vaccinated with vaccinia who has skin lesions, or been exposed directly to accidental splash of the vaccine.
- Have signs and symptoms consistent with ocular vaccinia.
- To be eligible for randomization the participant must have corneal involvement defined as a keratitis with any abnormality of the epithelium, stroma, or endothelium consistent with vaccinia infection.
Who cannot join
- To be randomized to the VIGIV/placebo treatment, a proposed participant must not satisfy the following exclusion criteria:
- Children with body weight less than 10 kg.
- Have a known severe reaction to the IV or IM administration of human immunoglobulin.
- Have known severe acute allergic reactions to the non-active ingredients of polysorbate 80, maltose, or the trace amounts of TNBP or Triton X-100 used in the preparation of VIGIV.
- Has received VIGIV within 6 months prior to randomization.
- Pregnant women, unless an approved, specific additional consent statement attesting to awareness of the unknown risk of VIGIV therapy during pregnancy is understood and signed by the participant.
- Have orbital cellulites.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Evaluation and Treatment of Ocular Complications of Vaccinia Vaccination: Suitability of NP-016 Vaccinia Immune Globulin (VIG) for Sight-Threatening Conditions [VIG31]
This study will evaluate patients with eye complications related to vaccination against smallpox to learn more about these conditions. Vaccinia vaccination has been used for more than 100 years for preventing smallpox. A small number of people who receive the vaccination (less than 1 in 1,000) develop complications, sometimes in their eyes. This usually results from the accidental transfer of the infection from the vaccination site to the face or eyes, perhaps by touching the vaccination area and then the face or eyelids before washing the hands. The study will also examine whether an experimental treatment called NP-016 vaccinia immune globulin can reduce corneal scarring that is sometimes associated with serious vaccinia complications and can impair vision.
Children and adults with keratitis, severe conjunctivitis, or blepharitis following exposure to vaccinia vaccination may be eligible for this study. Children must weigh at least 10 kg.
Read more
Participants undergo the following tests and procedures at enrollment, with some tests repeated at scheduled study visits:
- Medical history and physical examination
- Infectious disease consultation
- Complete eye evaluation including:
- Fundus photography to examine the back of the eye - dilation of the pupils with eye drops to examine and photograph the back of the eye
- Slit lamp biomicroscopy - evaluation of the front part of the eye with a slit lamp microscope
- Eye pressure measurements
- Eye swab to look for vaccinia virus or other causes of disease
- Blood tests
- Photographs and documentation of eye and skin lesions
- Vaccinia diagnostic tests, such as skin or mucosa scrapings; blood, throat, or urine cultures; and tissue biopsies, if needed
Patients begin treatment with standard medications for their eye disease, such as trifluridine (Viroptic® (Registered Trademark)) anti-viral eye drops. Patients whose condition becomes serious are offered additional treatment with intravenous (through a vein) infusions of either VIG or placebo (salt water solution with no active drug) and are randomly assigned to one or the other treatment group. All patients continue standard-of-care treatment as well.
Follow-up visits at the NIH eye clinic are scheduled as required by the patient's condition. Patients with mild complications who are taking only standard medications may need to be seen only 1 month after the initial visit and then 6 months and 12 months later. Patients with more serious conditions who qualify for VIG or placebo treatments may be seen daily for a week, then once a week for the rest of the first month, and then at 6 months and 12 months, unless more frequent treatment or observation is required.
Read the detailed description
Vaccinia virus (a live but relatively weak relative of smallpox and cowpox) is used to vaccinate people against the development of smallpox (variola) resulting from an infection with the viral genus Orthopoxvirus. Although, smallpox was thought to be eradicated worldwide during the 1970's, some smallpox cultures have been retained in the laboratories of several countries and may pose a potential threat if used as a biological weapon. This has recently led to programs where mass-inoculations with vaccinia have been initiated throughout the U.S.
Vaccination against smallpox using vaccinia can result in complications. Reactions are rarely serious or life threatening, but one of the most common serious complications occur in and around the eye. This occurs when a person transfers vaccinia viruses by touch from their primary inoculation site to their own eyes (auto-inoculation). Accidental exposure can also occur in the laboratory or by contact with a vaccinated person. Ocular involvement may be confined to the lids or conjunctiva but may easily be transferred to the cornea. Keratitis can result in scarring that could have a severe and permanent impact on vision. Even when the cornea is not affected, extensive lesions on the lid or other ocular tissues can lead to additional sight-threatening complications.
Recently, the US Food and Drug Administration licenced Vaccinia Immune Globulin Intravenous (Human) (VIGIV, formerly known as NP-016). It is indicated for the "treatment and/or modification of the following conditions, which are complications resulting from smallpox vaccination: (a) Eczema vaccinatum; (b) Progressive vaccinia; (c) Severe generalized vaccinia; (d) Vaccinia infections in individuals who have skin conditions such as burns, impetigo, varicella-zoster, or poison ivy; or individuals who have eczematous skin lesions because of either the activity or extensiveness of such lesions; and (e) Aberrant infections induced by vaccinia virus that includes its accidental implantation in eyes (except in cases of isolated keratitis), mouth, or other areas where vaccinia infection would constitute a special hazard." The precautionary statement regarding isolated vaccinia keratitis appears though it is uncertain whether VIGIV use will decrease or increase corneal scarring in humans. The implication of increased scarringis based on some evidence in animal models indicating that more extensive corneal clouding can occur following VIG therapy. To investigate if this implication has clinical significance, two hundred study participants with corneal involvement following vaccinia vaccination or other exposure will be randomized to receive either placebo or VIGIV. All enrolled participants will be provided standard-of-care antiviral treatments for ocular complications. One-year proportions of corneal scarring will be compared between the two groups. Further knowledge about the biologic mechanisms of complications associated with vaccinia vaccination and rapid diagnostic test may lead to more effective forms of therapy.
- Conditions
- Vaccinia
- Being tested
- NP-016 Vaccine Immune Globulin (IV-VIG)
- Keywords
- Smallpox, Cowpox, Corneal Ulcer, Keratitis, Immune Response, Vaccine, Cornea, Vaccinia, Vaccinia Immune Globulin (VIG), Conjunctivitis, Vaccinia Vaccination, Smallpox Vaccination
- Medical subject headings
- Vaccinia, Smallpox, Cowpox, Corneal Ulcer, Keratitis, Corneal Diseases, Conjunctivitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NP-016 Vaccine Immune Globulin (IV-VIG)Drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2004 (estimated)
- Study start19 Apr 2004
- Study completion15 Aug 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for VacciniaStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Enrolment
- 400 participants
Sponsor and investigators
- Lead sponsor
- National Eye Institute (NEI)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00081835
- Sponsor's protocol ID
- 040157
- Other IDs
- 04-EI-0157
- Status last verified
- 15 Aug 2007
- First submitted
- 22 Apr 2004
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Ruben FL, Lane JM. Ocular vaccinia. An epidemiologic analysis of 348 cases. Arch Ophthalmol. 1970 Jul;84(1):45-8. doi: 10.1001/archopht.1970.00990040047012. No abstract available.
PubMed 5423606
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation and Treatment of Ocular Complications of Vaccinia Vaccination: Suitability of NP-016 Vaccinia Immune Globulin (VIG) for Sight-Threatening Conditions [VIG31]
- ClinicalTrials.gov ID
- NCT00081835
- Acronym / sponsor ID
- 040157
- Conditions
- Vaccinia
- Keywords
- Smallpox, Cowpox, Corneal Ulcer, Keratitis, Immune Response, Vaccine, Cornea, Vaccinia, Vaccinia Immune Globulin (VIG)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 400 participants
- Lead sponsor
- National Eye Institute (NEI)US National Institutes of Health
- Study start
- 19 Apr 2004
- Study completion
- 15 Aug 2007
- First posted
- 22 Apr 2004 (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.
This study will evaluate patients with eye complications related to vaccination against smallpox to learn more about these conditions. Vaccinia vaccination has been used for more than 100 years for preventing smallpox. A small number of people who receive the vaccination (less than 1 in 1,000) develop complications, sometimes in their eyes. This usually results from the accidental transfer of the infection from the vaccination site to the face or eyes, perhaps by touching the vaccination area and then the face or eyelids before washing the hands. The study will also examine whether an experimental treatment called NP-016 vaccinia immune globulin can reduce corneal scarring that is sometimes associated with serious vaccinia complications and can impair vision.
Children and adults with keratitis, severe conjunctivitis, or blepharitis following exposure to vaccinia vaccination may be eligible for this study. Children must weigh at least 10 kg.
Participants undergo the following tests and procedures at enrollment, with some tests repeated at scheduled study visits:
- Medical history and physical examination
- Infectious disease consultation
- Complete eye evaluation including:
- Fundus photography to examine the back of the eye - dilation of the pupils with eye drops to examine and photograph the back of the eye
- Slit lamp biomicroscopy - evaluation of the front part of the eye with a slit lamp microscope
- Eye pressure measurements
- Eye swab to look for vaccinia virus or other causes of disease
- Blood tests
- Photographs and documentation of eye and skin lesions
- Vaccinia diagnostic tests, such as skin or mucosa scrapings; blood, throat, or urine cultures; and tissue biopsies, if needed
Patients begin treatment with standard medications for their eye disease, such as trifluridine (Viroptic® (Registered Trademark)) anti-viral eye drops. Patients whose condition becomes serious are offered additional treatment with intravenous (through a vein) infusions of either VIG or placebo (salt water solution with no active drug) and are randomly assigned to one or the other treatment group. All patients continue standard-of-care treatment as well.
Follow-up visits at the NIH eye clinic are scheduled as required by the patient's condition. Patients with mild complications who are taking only standard medications may need to be seen only 1 month after the initial visit and then 6 months and 12 months later. Patients with more serious conditions who qualify for VIG or placebo treatments may be seen daily for a week, then once a week for the rest of the first month, and then at 6 months and 12 months, unless more frequent treatment or observation is required.
Detailed description
Vaccinia virus (a live but relatively weak relative of smallpox and cowpox) is used to vaccinate people against the development of smallpox (variola) resulting from an infection with the viral genus Orthopoxvirus. Although, smallpox was thought to be eradicated worldwide during the 1970's, some smallpox cultures have been retained in the laboratories of several countries and may pose a potential threat if used as a biological weapon. This has recently led to programs where mass-inoculations with vaccinia have been initiated throughout the U.S.
Vaccination against smallpox using vaccinia can result in complications. Reactions are rarely serious or life threatening, but one of the most common serious complications occur in and around the eye. This occurs when a person transfers vaccinia viruses by touch from their primary inoculation site to their own eyes (auto-inoculation). Accidental exposure can also occur in the laboratory or by contact with a vaccinated person. Ocular involvement may be confined to the lids or conjunctiva but may easily be transferred to the cornea. Keratitis can result in scarring that could have a severe and permanent impact on vision. Even when the cornea is not affected, extensive lesions on the lid or other ocular tissues can lead to additional sight-threatening complications.
Recently, the US Food and Drug Administration licenced Vaccinia Immune Globulin Intravenous (Human) (VIGIV, formerly known as NP-016). It is indicated for the "treatment and/or modification of the following conditions, which are complications resulting from smallpox vaccination: (a) Eczema vaccinatum; (b) Progressive vaccinia; (c) Severe generalized vaccinia; (d) Vaccinia infections in individuals who have skin conditions such as burns, impetigo, varicella-zoster, or poison ivy; or individuals who have eczematous skin lesions because of either the activity or extensiveness of such lesions; and (e) Aberrant infections induced by vaccinia virus that includes its accidental implantation in eyes (except in cases of isolated keratitis), mouth, or other areas where vaccinia infection would constitute a special hazard." The precautionary statement regarding isolated vaccinia keratitis appears though it is uncertain whether VIGIV use will decrease or increase corneal scarring in humans. The implication of increased scarringis based on some evidence in animal models indicating that more extensive corneal clouding can occur following VIG therapy. To investigate if this implication has clinical significance, two hundred study participants with corneal involvement following vaccinia vaccination or other exposure will be randomized to receive either placebo or VIGIV. All enrolled participants will be provided standard-of-care antiviral treatments for ocular complications. One-year proportions of corneal scarring will be compared between the two groups. Further knowledge about the biologic mechanisms of complications associated with vaccinia vaccination and rapid diagnostic test may lead to more effective forms of therapy.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 1 year and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- To be eligible to enroll in this study, a prospective participant must satisfy all of the following inclusion criteria:
- The participant, or their parent or guardian if younger than 18 years at enrollment, is able to understand and sign an approved consent form. Any minor participant with adequate reading and writing skills must also sign an assent using a form approved by the local Institutional Review Board or Independent Ethics Committee (IRB/IEC). Minors with verbal skills but without adequate reading and writing skills should have an acknowledgement signed by their parent or guardian to certify that verbal assent to participate was obtained.
- The participant must have received the vaccinia vaccination, been exposed to a person vaccinated with vaccinia who has skin lesions, or been exposed directly to accidental splash of the vaccine.
- Have signs and symptoms consistent with ocular vaccinia.
- To be eligible for randomization the participant must have corneal involvement defined as a keratitis with any abnormality of the epithelium, stroma, or endothelium consistent with vaccinia infection.
Key exclusion criteria (7 listed)
- To be randomized to the VIGIV/placebo treatment, a proposed participant must not satisfy the following exclusion criteria:
- Children with body weight less than 10 kg.
- Have a known severe reaction to the IV or IM administration of human immunoglobulin.
- Have known severe acute allergic reactions to the non-active ingredients of polysorbate 80, maltose, or the trace amounts of TNBP or Triton X-100 used in the preparation of VIGIV.
- Has received VIGIV within 6 months prior to randomization.
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 |
|---|---|---|
| NP-016 Vaccine Immune Globulin (IV-VIG) | Drug | – |
Primary outcome
Not reported in the source record.
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 2 Jul 2017.
- Background: PubMed 5423606Ruben FL, Lane JM. Ocular vaccinia. An epidemiologic analysis of 348 cases. Arch Ophthalmol. 1970 Jul;84(1):45-8. doi: 10.1001/archopht.1970.00990040047012. No abstract available.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing NP-016 Vaccine Immune Globulin (IV-VIG) in people with Vaccinia, run by National Eye Institute (NEI) 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 5 inclusion and 7 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 2 Jul 2017. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00081835, which also lists 1 linked publication.
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 2 Jul 2017.