HIV InfectionsPhase 2/3MACRTNCT00000135
Studies of the Ocular Complications of AIDS (SOCA)--Monoclonal Antibody CMV Retinitis Trial (MACRT)
A Phase 2/3 study testing MSL-109 in people with HIV Infections and Cytomegalovirus Retinitis, run by Johns Hopkins Bloomberg School of Public Health.
Trial summary
To evaluate the efficacy and safety of a human anti-CMV monoclonal antibody, MSL-109, as adjunct therapy for controlling CMV retinitis. Read more about this study
- Who is it for?
- Ages 13 years and older
- Conditions the study is for
- HIV Infections, Cytomegalovirus Retinitis
- What is being tested?
- MSL-109
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 209 participants
- Where
- No sites listed yet
- Study dates
- Sep 1995to Aug 1996
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 13 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 13 years or older at entry
- Diagnosis of AIDS according to the Centers for Disease Control and Prevention (CDC) definition
- Diagnosis of active CMV retinitis as determined by a SOCA-certified ophthalmologist at time of enrollment
- At least one lesion whose size is one-quarter or more optic disc area
- Currently receiving (for relapsed patients) or scheduled to receive (for newly diagnosed patients) drugs for primary treatment of CMV retinitis that are not contraindicated for use with MSL-109
- Visual acuity, in at least one eye that meets other eligibility criteria, of 3 or more letters on ETDRS chart at 1 meter distance (Snellen equivalent 5/200). Patients with poorer visual acuity may be enrolled if the visual acuity impairment is possibly reversible (eg, due to optic disc edema) and vision is at least light perception in that eye
Show all 9Show fewer
- Karnofsky score of 60 or more
- Willingness and ability, with the assistance of a caregiver if necessary, to comply with treatment and follow up procedures
- signed consent statement
Who cannot join
- Current treatment with intravenous immune globulin (IVIG), CMV immune globulin (CMVIG), alpha-interferon (alpha-IFN), gamma-interferon (gamma-IFN) or interleukin-2 (IL-2)
- Media opacity that precludes visualization of the fundus in all eyes meeting eligibility criteria
- Active medical problems, including drug or alcohol abuse, that are considered sufficient to hinder compliance with treatment or follow up procedures
- Retinal detachment, not scheduled for surgical repair, in all eyes meeting other eligibility criteria
About this study
Official title: Monoclonal Antibody CMV Retinitis Trial (MACRT)
To evaluate the efficacy and safety of a human anti-CMV monoclonal antibody, MSL-109, as adjunct therapy for controlling CMV retinitis.
Read the detailed description
CMV retinitis is the most common intraocular infection in patients with AIDS and is estimated to affect 35 to 40 percent of patients with AIDS. Untreated CMV retinitis is a progressive disorder, the end result of which is total retinal destruction and blindness. As of September 1996, drugs approved by the United States Food and Drug Administration (FDA) for the treatment of CMV retinitis were ganciclovir (Cytovene), foscarnet (Foscavir), and cidofovir (Vistide). All systemically administered anti-CMV drugs are given in a similar fashion consisting of initial 2-week high-dose treatment (induction) to control the infection followed by long-term lower dose treatment (maintenance) to prevent relapse. Ganciclovir is available in both intravenous and oral formulations, foscarnet only in an intravenous formulation, and cidofovir is given by intermittent intravenous administration. A surgically implanted intraocular sustained-release ganciclovir device (Vitrasert) is also approved by the FDA for the treatment of CMV retinitis.
Despite the use of continuous maintenance therapy, given enough time, all patients with CMV retinitis on systemically administered drugs relapse. Preliminary studies suggested that the anti-CMV monoclonal antibody, MSL-109, when administered in conjunction with ganciclovir, markedly prolonged the time to relapse. Therefore, a randomized controlled clinical trial evaluating MSL-109 as adjunct therapy was conducted.
The MACRT was a randomized, placebo-controlled, multicenter clinical trial evaluating the efficacy and safety of MSL-109 as adjunct therapy for the treatment of CMV retinitis. Patients with CMV retinitis, both those newly diagnosed and those suffering a relapse with active retinitis, were eligible. Primary therapy (e.g., ganciclovir, foscarnet, etc.) was determined by the treating local physician. The patients enrolled in the trial were randomized to either MSL-109 or placebo, administered as a rapid intravenous infusion every 2 weeks. Outcomes included survival, retinitis progression, change in amount of retinal area involved by CMV, loss of visual function (acuity and field), and morbidity.
- Conditions
- HIV Infections, Cytomegalovirus Retinitis
- Being tested
- MSL-109, Placebo
- Medical subject headings
- HIV Infections, Cytomegalovirus Retinitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MSL-109Drug
Also called Monoclonal antibodies
60 mg, IV (in vein) every two weeks, treatment continued until death or common closeout.
PlaceboOther
60 mg, IV (in vein) every two weeks, treatment continued until death or common closeout.
| Study group | Role | What they receive |
|---|---|---|
| MSL-109 | Experimental | The dose MSL-109 administered by intravenous infusion every 2 weeks 60 mg. Receives: Drug: MSL-109 |
| Placebo | Placebo comparator | Placebo administered intravenous infusion every 2 weeks 60 mg. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mortality Rate
to evaluate the efficacy of an intravenous human monoclonal antibody to cytomegalovirus (CMV), MSL-109, as adjuvant treatment for CMV retinitis. .
Measured: All patients enrolled were followed for a 17 month period or until a common study closing date
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 1999 (estimated)
- Study startSep 1995
- Primary completionAug 1996
- Study completionAug 1996
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by Johns Hopkins Bloomberg School of Public HealthThe 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 209 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins Bloomberg School of Public Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00000135
- Sponsor's protocol ID
- NEI-34
- Acronym
- MACRT
- Status last verified
- Jul 2015
- First submitted
- 23 Sep 1999
- Last updated
- 17 Nov 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
MSL-109 adjuvant therapy for cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome: the Monoclonal Antibody Cytomegalovirus Retinitis Trial. The Studies of Ocular Complications of AIDS Research Group. AIDS Clinical Trials Group. Arch Ophthalmol. 1997 Dec;115(12):1528-36.
PubMed 9400786Jabs DA, Gilpin AM, Min YI, Erice A, Kempen JH, Quinn TC; Studies of Ocular Complications of AIDS Research Group. HIV and cytomegalovirus viral load and clinical outcomes in AIDS and cytomegalovirus retinitis patients: Monoclonal Antibody Cytomegalovirus Retinitis Trial. AIDS. 2002 Apr 12;16(6):877-87. doi: 10.1097/00002030-200204120-00007.
PubMed 11919489Davidson M, Min YI, Holbrook JT, Van Natta M, Quinn TC, Murphy RL, Welch W, Jabs DA, Meinert CL; Studies of Ocular Complications of AIDS Research Group. Influence of filgrastim (granulocyte colony-stimulating factor) on human immunodeficiency virus type 1 RNA in patients with cytomegalovirus retinitis. J Infect Dis. 2002 Oct 1;186(7):1013-8. doi: 10.1086/342956. Epub 2002 Aug 29.
PubMed 12232843Gilpin AM, Holbrook JT, Jabs DA, Meinert CL; Studies of Ocular Complications of AIDS Research Group. Data and safety monitoring board deliberations resulting in the early termination of the Monoclonal Antibody Cytomegalovirus Retinitis Trial. Control Clin Trials. 2003 Feb;24(1):92-8. doi: 10.1016/s0197-2456(02)00268-4.
PubMed 12559647Holland GN, Van Natta ML, Goldenberg DT, Ritts R Jr, Danis RP, Jabs DA; Studies of Ocular Complications of AIDS Research Group. Relationship Between Opacity of Cytomegalovirus Retinitis Lesion Borders and Severity of Immunodeficiency Among People With AIDS. Invest Ophthalmol Vis Sci. 2019 May 1;60(6):1853-1862. doi: 10.1167/iovs.18-26517.
PubMed 31042791
Study at a glance
From the registry record, last updated by the sponsor on 17 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Monoclonal Antibody CMV Retinitis Trial (MACRT)
- ClinicalTrials.gov ID
- NCT00000135
- Acronym / sponsor ID
- MACRT / NEI-34
- Conditions
- HIV Infections, Cytomegalovirus Retinitis
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 209 participants (actual)
- Lead sponsor
- Johns Hopkins Bloomberg School of Public HealthUniversity, hospital or other
- Study start
- Sep 1995
- Primary completion
- Aug 1996 (actual)
- Study completion
- Aug 1996 (actual)
- First posted
- 24 Sep 1999 (estimated)
- Results
- Posted 17 Nov 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate the efficacy and safety of a human anti-CMV monoclonal antibody, MSL-109, as adjunct therapy for controlling CMV retinitis.
Detailed description
CMV retinitis is the most common intraocular infection in patients with AIDS and is estimated to affect 35 to 40 percent of patients with AIDS. Untreated CMV retinitis is a progressive disorder, the end result of which is total retinal destruction and blindness. As of September 1996, drugs approved by the United States Food and Drug Administration (FDA) for the treatment of CMV retinitis were ganciclovir (Cytovene), foscarnet (Foscavir), and cidofovir (Vistide). All systemically administered anti-CMV drugs are given in a similar fashion consisting of initial 2-week high-dose treatment (induction) to control the infection followed by long-term lower dose treatment (maintenance) to prevent relapse. Ganciclovir is available in both intravenous and oral formulations, foscarnet only in an intravenous formulation, and cidofovir is given by intermittent intravenous administration. A surgically implanted intraocular sustained-release ganciclovir device (Vitrasert) is also approved by the FDA for the treatment of CMV retinitis.
Despite the use of continuous maintenance therapy, given enough time, all patients with CMV retinitis on systemically administered drugs relapse. Preliminary studies suggested that the anti-CMV monoclonal antibody, MSL-109, when administered in conjunction with ganciclovir, markedly prolonged the time to relapse. Therefore, a randomized controlled clinical trial evaluating MSL-109 as adjunct therapy was conducted.
The MACRT was a randomized, placebo-controlled, multicenter clinical trial evaluating the efficacy and safety of MSL-109 as adjunct therapy for the treatment of CMV retinitis. Patients with CMV retinitis, both those newly diagnosed and those suffering a relapse with active retinitis, were eligible. Primary therapy (e.g., ganciclovir, foscarnet, etc.) was determined by the treating local physician. The patients enrolled in the trial were randomized to either MSL-109 or placebo, administered as a rapid intravenous infusion every 2 weeks. Outcomes included survival, retinitis progression, change in amount of retinal area involved by CMV, loss of visual function (acuity and field), and morbidity.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MSL-109 | Experimental | Drug: MSL-109The dose MSL-109 administered by intravenous infusion every 2 weeks 60 mg. |
| Placebo | Placebo comparator | Other: PlaceboPlacebo administered intravenous infusion every 2 weeks 60 mg. |
Who may qualify
- Ages
- 13 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- 13 years or older at entry
- Diagnosis of AIDS according to the Centers for Disease Control and Prevention (CDC) definition
- Diagnosis of active CMV retinitis as determined by a SOCA-certified ophthalmologist at time of enrollment
- At least one lesion whose size is one-quarter or more optic disc area
- Currently receiving (for relapsed patients) or scheduled to receive (for newly diagnosed patients) drugs for primary treatment of CMV retinitis that are not contraindicated for use with MSL-109
Key exclusion criteria (4 listed)
- Current treatment with intravenous immune globulin (IVIG), CMV immune globulin (CMVIG), alpha-interferon (alpha-IFN), gamma-interferon (gamma-IFN) or interleukin-2 (IL-2)
- Media opacity that precludes visualization of the fundus in all eyes meeting eligibility criteria
- Active medical problems, including drug or alcohol abuse, that are considered sufficient to hinder compliance with treatment or follow up procedures
- Retinal detachment, not scheduled for surgical repair, in all eyes meeting other eligibility criteria
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 |
|---|---|---|
| MSL-109Also: Monoclonal antibodies60 mg, IV (in vein) every two weeks, treatment continued until death or common closeout. | Drug | MSL-109 |
| Placebo60 mg, IV (in vein) every two weeks, treatment continued until death or common closeout. | Other | Placebo |
Primary outcome
Mortality Rate
Time frame: All patients enrolled were followed for a 17 month period or until a common study closing date
to evaluate the efficacy of an intravenous human monoclonal antibody to cytomegalovirus (CMV), MSL-109, as adjuvant treatment for CMV retinitis. .
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Nov 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 9400786MSL-109 adjuvant therapy for cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome: the Monoclonal Antibody Cytomegalovirus Retinitis Trial. The Studies of Ocular Complications of AIDS Research Group. AIDS Clinical Trials Group. Arch Ophthalmol. 1997 Dec;115(12):1528-36.
- Results publication: PubMed 11919489Jabs DA, Gilpin AM, Min YI, Erice A, Kempen JH, Quinn TC; Studies of Ocular Complications of AIDS Research Group. HIV and cytomegalovirus viral load and clinical outcomes in AIDS and cytomegalovirus retinitis patients: Monoclonal Antibody Cytomegalovirus Retinitis Trial. AIDS. 2002 Apr 12;16(6):877-87. doi: 10.1097/00002030-200204120-00007.
- Results publication: PubMed 12232843Davidson M, Min YI, Holbrook JT, Van Natta M, Quinn TC, Murphy RL, Welch W, Jabs DA, Meinert CL; Studies of Ocular Complications of AIDS Research Group. Influence of filgrastim (granulocyte colony-stimulating factor) on human immunodeficiency virus type 1 RNA in patients with cytomegalovirus retinitis. J Infect Dis. 2002 Oct 1;186(7):1013-8. doi: 10.1086/342956. Epub 2002 Aug 29.
- Results publication: PubMed 12559647Gilpin AM, Holbrook JT, Jabs DA, Meinert CL; Studies of Ocular Complications of AIDS Research Group. Data and safety monitoring board deliberations resulting in the early termination of the Monoclonal Antibody Cytomegalovirus Retinitis Trial. Control Clin Trials. 2003 Feb;24(1):92-8. doi: 10.1016/s0197-2456(02)00268-4.
- Derived from this study: PubMed 31042791Holland GN, Van Natta ML, Goldenberg DT, Ritts R Jr, Danis RP, Jabs DA; Studies of Ocular Complications of AIDS Research Group. Relationship Between Opacity of Cytomegalovirus Retinitis Lesion Borders and Severity of Immunodeficiency Among People With AIDS. Invest Ophthalmol Vis Sci. 2019 May 1;60(6):1853-1862. doi: 10.1167/iovs.18-26517.
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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.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing MSL-109 in people with HIV Infections and Cytomegalovirus Retinitis, run by Johns Hopkins Bloomberg School of Public Health.
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 9 inclusion and 4 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 17 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Nov 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Mortality Rate (time frame: All patients enrolled were followed for a 17 month period or until a common study closing date). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00000135, which also lists 5 linked publications.
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 17 Nov 2015.