Pneumonia, Interstitial Plasma CellPhase 3NCT00302341
DB289 Versus TMP-SMX for the Treatment of Acute Pneumocystis Jiroveci Pneumonia (PCP)
A Phase 3 study testing Pafuramidine maleate (DB289) and Trimethoprim-Sulfamethoxazole (TMP-SMX) in people with Pneumonia, Interstitial Plasma Cell and Pneumocystis Carinii Pneumonia, run by Immtech Pharmaceuticals, Inc at 7 sites in United States.
Trial summary
The purpose of this study is to demonstrate the non-inferiority of pafuramidine maleate (DB289)versus trimethoprim-sulfamethoxazole (TMP-SMX)for the treatment of mild to moderately severe Pneumocystis pneumonia (PCP). Read more about this study
- Who is it for?
- Ages 13 to 65 years
- Conditions the study is for
- Pneumonia, Interstitial Plasma Cell, Pneumocystis Carinii Pneumonia, Pneumonia, Pneumocystis Carinii
- What is being tested?
- Pafuramidine maleate (DB289) and Trimethoprim-Sulfamethoxazole (TMP-SMX)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 7 sitesUnited States
- Study dates
- May 2006to Dec 2008
- Phase
- Phase 3
- 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 13 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Documented or presumptive HIV infection
- Signs and symptoms of PCP present for at least 5 days
- Pneumocystis jiroveci confirmed in BAL fluid or induced sputum sample
- Suitable candidate for oral therapy
- Alveolar-arterial oxygen (A-a) gradient < or = 45 mm Hg on room air and partial pressure of oxygen (pO2) > or = 60 mm Hg
- No more than 48 hours of prior treatment in the preceding 7 days for PCP treatment at full doses; failure of Pneumocystis prophylaxis or use of medications recommended for treatment of PCP at doses less than recommended by the CDC Guidelines is acceptable.
Who cannot join
- Unwilling or unable to discontinue use of other medications with anti-PCP activity
- AIDS related cachexia (weight loss that is more than 10% of ideal body weight)
- Severe diarrhea and/or vomiting
- History of hypersensitivity or severe or life threatening toxicity to TMP-SMX, other sulfonamides or pentamidine
- Active illicit drug use
- Impending respiratory failure or need for intubation
Show all 16Show fewer
- AST and ALT levels > 3 times the upper limit of normal
- History of pancreatitis
- Severe PCP
- Karnofsky score < or = 20
- Terminal HIV disease or life expectancy of less than 6 months
- Acute concurrent pulmonary pathological condition that would obscure the evaluation of response to therapy
- Concomitant use of amphotericin B, gangciclovir, cyclosporine, warfarin, thiazide diuretics, phenytoin, methotrexate, leucovorin
- Receipt of systemic corticosteroids (except replacement therapy) within 14 days of study entry at high doses for 3 or more consecutive days. Concomitant use of corticosteroids, other than replacement doses for adrenal insufficiency, is also excluded unless the patient meets the CDC criteria for use of corticosteroids for treatment of PCP
- Pregnant or lactating women
- The subject has been previously enrolled in the study
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
UNC AIDS Clinical Trials
Chapel Hill, North Carolina, 27599-7030
Medical University of SC
Charleston, South Carolina, 29425
The University of Chicago
Chicago, Illinois, 60637
University of Cincinnati
Cincinnati, Ohio, 45267-0405
Henry Ford Health System
Detroit, Michigan, 48202
NYU School of Medicine
New York, New York, 10016
University of California
San Francisco, California, 94110
About this study
Official title: International Randomized, Controlled Phase 3 Trial of DB289 Versus Trimethoprim-sulfamethoxazole for the Treatment of Acute Pneumocystis Jiroveci Pneumonia (PCP) in Patients With HIV/AIDS
The purpose of this study is to demonstrate the non-inferiority of pafuramidine maleate (DB289)versus trimethoprim-sulfamethoxazole (TMP-SMX)for the treatment of mild to moderately severe Pneumocystis pneumonia (PCP).
Read the detailed description
The gold standard treatment for PCP is trimethoprim-sulfamethoxazole (TMP-SMX). This drug is highly effective; however, a significant number of patients are unable to complete a course of therapy due to adverse events, some of which can be life-threatening. In addition, mutations that confer resistance to sulfa-based drugs in other microorganisms are increasingly being reported in P. jiroveci. A potential role of these mutations in conferring clinical resistance to PCP and in breakthroughs to prophylaxis regimens based on sulfa drugs is being actively studied. Second and third line agents or combinations for PCP treatment are also limited in efficacy and/or by adverse events.
A new agent such as pafuramidine maleate (DB289), which has well documented activity against P. carinii in animal models, documented efficacy in a preliminary study trial in HIV-infected patients with PCP that were intolerant or resistant to TMP-SMX, was well tolerated in this trial and demonstrated a low toxicity profile in Phase 1 studies, would meet a significant medical need. Furthermore, pafuramidine maleate is active against other pathogens responsible for significant morbidity and mortality in patients with AIDS in the developing world, like different strains of Plasmodium (malaria) and Cryptosporidium parvum. The decrease in the rate of PCP in countries where patients with AIDS have access to HAART will present a significant challenge to the completion of this development program. The last published trial of PCP treatment was conducted by the ACTG in 24 U.S. sites between May 1991 and june 1993. That study needed to decrease the planned sample size to 195 due to low enrollment. This represents an important challenge for our program.
- Conditions
- Pneumonia, Interstitial Plasma Cell, Pneumocystis Carinii Pneumonia, Pneumonia, Pneumocystis Carinii, HIV Infections
- Being tested
- Pafuramidine maleate (DB289), Trimethoprim-Sulfamethoxazole (TMP-SMX)
- Keywords
- Pulmonary disease, Dyspnea, Hypoxemia, AIDS, Pneumocystis jiroveci
- Medical subject headings
- Pneumonia, Pneumocystis, HIV Infections, Lung Diseases, Dyspnea, Hypoxia, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pafuramidine maleate (DB289)Drug
Oral tablet, 100 mg bid, 14 days
Trimethoprim-Sulfamethoxazole (TMP-SMX)Drug
Also called Bactrim
15 mg/kg, oral tablet split tid X 21 days
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | pafuramidine maleate, oral tablet, 100 mg bid X 14 days Receives: Drug: Pafuramidine maleate (DB289) |
| 2 | Active comparator | TMP/SMX oral tablet, 15 mg/kg, split tid X 21 days Receives: Drug: Trimethoprim-Sulfamethoxazole (TMP-SMX) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary efficacy endpoint will be the proportion of subjects with clinical success at the End of Treatment (Day 22) for the Modified Intent-to-Treat population (mITT).
Measured: Day 22
Secondary outcomes (1)
The secondary efficacy endpoints will be the proportion of subjects with clinical success at the End of Treatment (Day 22)for the Per Protocol population and sustained clinical success at the End of Study (Day 42)in the Per Protocol and mITT populations.
Measured: Day 22
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2006 (estimated)
- Study startMay 2006
- Primary completionDec 2008
- Study completionDec 2008
Why it stopped: FDA Clinical Hold as of 12/21/07 due to safety concerns
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pneumonia, Interstitial Plasma CellStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Immtech Pharmaceuticals, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Judith Aberg, MD, Principal investigator, NYU School of MedicinePreston Church, MD, Principal investigator, Medical University of South CarolinaLaurence Huang, MD, Principal investigator, University of California, San FranciscoAmanda Peppercorn, MD, Principal investigator, UNC AIDS Clinical Trials- School of MedicineCarl Fichtenbaum, MD, Principal investigator, University of CincinnatiKathleen Mullane, DO, Principal investigator, University of ChicagoJose Vazquez, MD, Principal investigator, Henry Ford Health Systems
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00302341
- Sponsor's protocol ID
- C05-009
- Status last verified
- Mar 2013
- First submitted
- 10 Mar 2006
- Last updated
- 7 Mar 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- International Randomized, Controlled Phase 3 Trial of DB289 Versus Trimethoprim-sulfamethoxazole for the Treatment of Acute Pneumocystis Jiroveci Pneumonia (PCP) in Patients With HIV/AIDS
- ClinicalTrials.gov ID
- NCT00302341
- Acronym / sponsor ID
- C05-009
- Conditions
- Pneumonia, Interstitial Plasma Cell, Pneumocystis Carinii Pneumonia, Pneumonia, Pneumocystis Carinii, HIV Infections
- Keywords
- Pulmonary disease, Dyspnea, Hypoxemia, AIDS, Pneumocystis jiroveci
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: FDA Clinical Hold as of 12/21/07 due to safety concerns
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Immtech Pharmaceuticals, IncIndustry (pharma, biotech, devices)
- Study start
- May 2006
- Primary completion
- Dec 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 14 Mar 2006 (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.
The purpose of this study is to demonstrate the non-inferiority of pafuramidine maleate (DB289)versus trimethoprim-sulfamethoxazole (TMP-SMX)for the treatment of mild to moderately severe Pneumocystis pneumonia (PCP).
Detailed description
The gold standard treatment for PCP is trimethoprim-sulfamethoxazole (TMP-SMX). This drug is highly effective; however, a significant number of patients are unable to complete a course of therapy due to adverse events, some of which can be life-threatening. In addition, mutations that confer resistance to sulfa-based drugs in other microorganisms are increasingly being reported in P. jiroveci. A potential role of these mutations in conferring clinical resistance to PCP and in breakthroughs to prophylaxis regimens based on sulfa drugs is being actively studied. Second and third line agents or combinations for PCP treatment are also limited in efficacy and/or by adverse events.
A new agent such as pafuramidine maleate (DB289), which has well documented activity against P. carinii in animal models, documented efficacy in a preliminary study trial in HIV-infected patients with PCP that were intolerant or resistant to TMP-SMX, was well tolerated in this trial and demonstrated a low toxicity profile in Phase 1 studies, would meet a significant medical need. Furthermore, pafuramidine maleate is active against other pathogens responsible for significant morbidity and mortality in patients with AIDS in the developing world, like different strains of Plasmodium (malaria) and Cryptosporidium parvum. The decrease in the rate of PCP in countries where patients with AIDS have access to HAART will present a significant challenge to the completion of this development program. The last published trial of PCP treatment was conducted by the ACTG in 24 U.S. sites between May 1991 and june 1993. That study needed to decrease the planned sample size to 195 due to low enrollment. This represents an important challenge for our program.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Pafuramidine maleate (DB289)pafuramidine maleate, oral tablet, 100 mg bid X 14 days |
| 2 | Active comparator | Drug: Trimethoprim-Sulfamethoxazole (TMP-SMX)TMP/SMX oral tablet, 15 mg/kg, split tid X 21 days |
Who may qualify
- Ages
- 13 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Documented or presumptive HIV infection
- Signs and symptoms of PCP present for at least 5 days
- Pneumocystis jiroveci confirmed in BAL fluid or induced sputum sample
- Suitable candidate for oral therapy
- Alveolar-arterial oxygen (A-a) gradient < or = 45 mm Hg on room air and partial pressure of oxygen (pO2) > or = 60 mm Hg
Key exclusion criteria (16 listed)
- Unwilling or unable to discontinue use of other medications with anti-PCP activity
- AIDS related cachexia (weight loss that is more than 10% of ideal body weight)
- Severe diarrhea and/or vomiting
- History of hypersensitivity or severe or life threatening toxicity to TMP-SMX, other sulfonamides or pentamidine
- Active illicit drug use
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 |
|---|---|---|
| Pafuramidine maleate (DB289)Oral tablet, 100 mg bid, 14 days | Drug | 1 |
| Trimethoprim-Sulfamethoxazole (TMP-SMX)Also: Bactrim15 mg/kg, oral tablet split tid X 21 days | Drug | 2 |
Primary outcome
The primary efficacy endpoint will be the proportion of subjects with clinical success at the End of Treatment (Day 22) for the Modified Intent-to-Treat population (mITT).
Time frame: Day 22
1 secondary outcome
The secondary efficacy endpoints will be the proportion of subjects with clinical success at the End of Treatment (Day 22)for the Per Protocol population and sustained clinical success at the End of Study (Day 42)in the Per Protocol and mITT populations.
Time frame: Day 22
Results and safety
The study was stopped early (reason given: FDA Clinical Hold as of 12/21/07 due to safety concerns). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2013.
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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.
Judith Aberg, MD principal investigator
NYU School of Medicine
Preston Church, MD principal investigator
Medical University of South Carolina
Laurence Huang, MD principal investigator
University of California, San Francisco
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pafuramidine maleate (DB289) and Trimethoprim-Sulfamethoxazole (TMP-SMX) in people with Pneumonia, Interstitial Plasma Cell and Pneumocystis Carinii Pneumonia, run by Immtech Pharmaceuticals, Inc at 7 sites 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 6 inclusion and 16 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: stopped early, as of the sponsor's last update on 7 Mar 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites 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 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?
The study was stopped early (reason given: FDA Clinical Hold as of 12/21/07 due to safety concerns). Results are not available in the source record.
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?
The primary efficacy endpoint will be the proportion of subjects with clinical success at the End of Treatment (Day 22) for the Modified Intent-to-Treat population (mITT). (time frame: Day 22). 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 7 Mar 2013.