Dense Deposit DiseasePhase 1NCT01791686
Clinical Trial of CDX-1135 in Pediatric and Adult Patients With Dense Deposit Disease
A Phase 1 study testing CDX-1135 in people with Dense Deposit Disease and Membranoproliferative Glomerulonephritis Type II, run by Celldex Therapeutics at 1 site in United States.
Trial summary
This study is evaluating the study drug (CDX-1135) in patients with dense deposit disease (DDD). The objective is to evaluate the safety and activity of repeated doses of CDX-1135 in pediatric and adult patients with DDD. After screening, eligible patients will be entered into the Induction Period. Read more about this study
- Who is it for?
- Ages 4 years and older
- Conditions the study is for
- Dense Deposit Disease, Membranoproliferative Glomerulonephritis Type II, C3 Glomerulonephritis
- What is being tested?
- CDX-1135
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2013to Mar 2014
- 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 4 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Among other criteria, patients must be
- Patient and/or parent/legal guardian (as appropriate) must give written informed consent
- Four (4) years of age or older
- Must have DDD, confirmed by renal biopsy within 6 months of study enrollment (Confirmation by University of Iowa investigators is required). If the patient is post transplant, the repeat renal transplant biopsy must show C3 dominant glomerulonephritis, and the patient must have a history of known DDD in the native kidney
- Signs of abnormal complement pathway activity
- Serum creatinine level must be abnormal
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- Screening lab values criteria:
- Hgb ≥ 9.0 g/dL
- Platelets ≥ 100,000/mm^3
- ALT and AST ≤ 3.0 x upper limit of normal
- C3 serum <50% of the lower limit of normal
- 24 hour urine protein >1000 mg/day, or urine protein:creatinine ratio >1.0
- Both male and female patients of childbearing potential enrolled must use adequate birth control during the trial and for 1 month after stopping study drug
- Willing and able to comply with study procedures, including pre-study vaccinations (meningitis, haemophilus and pneumococci) and agree to a renal biopsy at Week 13 and at the end of the study
- Any anti-proteinuric medications (eg, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers) must be at a stable dose for 4 weeks prior to first dose of CDX-1135
Who cannot join
- Among other criteria, patients must not be
- Dialysis or a low estimated glomerular filtration rate <30 ml/min/1.73m^2 over a 4-week period prior to Screening
- Active or untreated systemic bacterial infection
- Pregnant or lactating
- Rituximab therapy (unless discontinued with B cell levels and immunoglobulin levels normalized by study entry)
- Immunosuppressive therapies (except for low dose steroids [≤10 mg per day] given for non-DDD related conditions such as asthma). Exceptions will be made for renal transplant patients, who may receive any appropriate therapies as needed to maintain the transplant (i.e., to prevent rejection)
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- Treatment with any complement inhibitor within 3 months of study entry or any other investigational drug, device, or experimental procedure within 4 weeks prior to enrollment
- For renal transplant patients only: histology findings of treatable rejection (i.e. that the usual transplant physician would seek to treat). Chronic allograft nephropathy is not exclusionary provided the patient's glomerular filtration rate meets other entry criteria
- Preexisting condition with an association as a potential cause of DDD (i.e., Monoclonal Gammopathy of Undetermined Significance) or an alternate glomerular disease
- Cancer except for adequately treated and cured basal or squamous cell skin cancer, curatively treated in situ disease, or other cancer that the patient has been disease-free for ≥ 5 years
- Myocardial infarction within 1 year of screening, congestive heart failure, arrhythmia persistent on medication at screening or chronic lung disease
- Known HIV, Hepatitis B or Hepatitis C
- Any medical or psychological condition that would increase the patient's risk by being in this study or would interfere with interpretation of the study
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Iowa Hospitals & Clinics
Iowa City, Iowa, 52242
About this study
Official title: A Pilot, Open-label, Multicenter Clinical Trial of CDX-1135 in Pediatric and Adult Patients With Dense Deposit Disease
This study is evaluating the study drug (CDX-1135) in patients with dense deposit disease (DDD). The objective is to evaluate the safety and activity of repeated doses of CDX-1135 in pediatric and adult patients with DDD. After screening, eligible patients will be entered into the Induction Period. The Induction Period is up to 4 weeks. Following normalization of complement activity, patients will enter into the Maintenance Period.The total treatment duration is up to 26 weeks.
- Conditions
- Dense Deposit Disease, Membranoproliferative Glomerulonephritis Type II, C3 Glomerulonephritis
- Being tested
- CDX-1135
- Keywords
- Dense Deposit Disease, DDD
- Medical subject headings
- Glomerulonephritis, Membranoproliferative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CDX-1135Drug
Also called TP10, sCR1
| Study group | Role | What they receive |
|---|---|---|
| Dense Deposit Disease | Experimental | ► Induction Period
Patients will receive CDX-1135 as an IV infusion twice weekly (Mon-Thur or Tues-Fri). There will be two doses of 5 mg/kg, with intrapatient dose-escalation in 5 mg/kg increments up to a maximum dose of 30 mg/kg. This period may last up to 8 weeks.
► Maintenance Period
The starting dose for CDX-1135 Maintenance will be the same dose level as the last dose during the Induction Period; however, the Maintenance Period allows for dose decrease to 2 mg/kg, which is lower than the starting dose in the Induction Period.
Patients will receive CDX-1135 as an IV infusion twice weekly (Mon-Thur or Tues-Fri) for up to a total of 26 weeks. Receives: Drug: CDX-1135 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety
- Incidence and severity of adverse events (AE) will be assessed at every visit. AEs and serious adverse events (SAEs) will be assessed from the first dose of study drug through 33 days after the last dose
- To evaluate the safety of repeated dosing in patients with DDD. Safety will be assessed based on changes in clinical laboratory tests, physical exams, vital signs, ophthalmic exams and ECGs [for patients ≥ 35 years of age].
Measured: From first study drug dose for up to 26 weeks
C3 and AP Normalization
The proportion of patients with normalization of serum C3, serum C3 breakdown products, or alternative pathway (AP) complement activity. These blood tests will be assessed on each dosing day and upon Study Completion /Termination.
Measured: Regular assessments from study start up to 26 weeks
Secondary outcomes (4)
Duration of and time to normalize C3 and AP
Time to normalization of serum levels of C3 or C3 breakdown products and duration of normalization and assays of alternative pathway activity. These blood tests will be assessed on each dosing day and upon Study Completion /Termination.
Measured: Regular assessments from study start up to 26 weeks
Renal Function
Stabilization and/or improvement in renal function (as measured by serum creatinine and proteinuria). These lab tests will be performed weekly during the Induction Period, monthly during the Maintenance Period and upon Study Completion /Termination.
Measured: Regularly from study start up to 26 weeks
Renal biopsy
Improvement on renal biopsy (as measured by reduction in C3 deposition in the glomerular basement membrane). This biopsy may be performed during screening, week 13, and upon Study Completion /Termination.
Measured: Occurs up to 3 times from study start up to 26 weeks
Immunogenicity
Immunogenicity (development of antibodies to CDX-1135). This sample will be collected prior to dosing on Week 1, monthly during treatment, and upon Study Completion /Termination
Measured: Regular assessments from study start up to 26 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2013 (estimated)
- Study startJan 2013
- Primary completionMar 2014
- Study completionMar 2014
Why it stopped: Portfolio prioritization due to slow enrollment and variable spectrum of potential complement abnormalities in DDD patients.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Dense Deposit DiseaseStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celldex Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Carla Nester, MD, MSA, Principal investigator, University of IowaRichard Smith, MD, Principal investigator, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01791686
- Sponsor's protocol ID
- CDX1135-01
- Status last verified
- Mar 2014
- First submitted
- 29 Jan 2013
- Last updated
- 7 Mar 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot, Open-label, Multicenter Clinical Trial of CDX-1135 in Pediatric and Adult Patients With Dense Deposit Disease
- ClinicalTrials.gov ID
- NCT01791686
- Acronym / sponsor ID
- CDX1135-01
- Conditions
- Dense Deposit Disease, Membranoproliferative Glomerulonephritis Type II, C3 Glomerulonephritis
- Keywords
- Dense Deposit Disease, DDD
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Portfolio prioritization due to slow enrollment and variable spectrum of potential complement abnormalities in DDD patients.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Celldex TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Jan 2013
- Primary completion
- Mar 2014 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 15 Feb 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.
This study is evaluating the study drug (CDX-1135) in patients with dense deposit disease (DDD). The objective is to evaluate the safety and activity of repeated doses of CDX-1135 in pediatric and adult patients with DDD. After screening, eligible patients will be entered into the Induction Period. The Induction Period is up to 4 weeks. Following normalization of complement activity, patients will enter into the Maintenance Period.The total treatment duration is up to 26 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dense Deposit Disease | Experimental | Drug: CDX-1135► Induction Period Patients will receive CDX-1135 as an IV infusion twice weekly (Mon-Thur or Tues-Fri). There will be two doses of 5 mg/kg, with intrapatient dose-escalation in 5 mg/kg increments up to a maximum dose of 30 mg/kg. This period may last up to 8 weeks. ► Maintenance Period The starting dose for CDX-1135 Maintenance will be the same dose level as the last dose during the Induction Period; however, the Maintenance Period allows for dose decrease to 2 mg/kg, which is lower than the starting dose in the Induction Period. Patients will receive CDX-1135 as an IV infusion twice weekly (Mon-Thur or Tues-Fri) for up to a total of 26 weeks. |
Who may qualify
- Ages
- 4 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (15 listed)
- Among other criteria, patients must be
- Patient and/or parent/legal guardian (as appropriate) must give written informed consent
- Four (4) years of age or older
- Must have DDD, confirmed by renal biopsy within 6 months of study enrollment (Confirmation by University of Iowa investigators is required). If the patient is post transplant, the repeat renal transplant biopsy must show C3 dominant glomerulonephritis, and the patient must have a history of known DDD in the native kidney
- Signs of abnormal complement pathway activity
Key exclusion criteria (13 listed)
- Among other criteria, patients must not be
- Dialysis or a low estimated glomerular filtration rate <30 ml/min/1.73m^2 over a 4-week period prior to Screening
- Active or untreated systemic bacterial infection
- Pregnant or lactating
- Rituximab therapy (unless discontinued with B cell levels and immunoglobulin levels normalized by study entry)
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 |
|---|---|---|
| CDX-1135Also: TP10, sCR1 | Drug | Dense Deposit Disease |
Primary outcome
Safety
Time frame: From first study drug dose for up to 26 weeks
* Incidence and severity of adverse events (AE) will be assessed at every visit. AEs and serious adverse events (SAEs) will be assessed from the first dose of study drug through 33 days after the last dose * To evaluate the safety of repeated dosing in patients with DDD. Safety will be assessed based on changes in clinical laboratory tests, physical exams, vital signs, ophthalmic exams and ECGs [for patients ≥ 35 years of age].
C3 and AP Normalization
Time frame: Regular assessments from study start up to 26 weeks
The proportion of patients with normalization of serum C3, serum C3 breakdown products, or alternative pathway (AP) complement activity. These blood tests will be assessed on each dosing day and upon Study Completion /Termination.
4 secondary outcomes
Duration of and time to normalize C3 and AP
Time frame: Regular assessments from study start up to 26 weeks
Renal Function
Time frame: Regularly from study start up to 26 weeks
Renal biopsy
Time frame: Occurs up to 3 times from study start up to 26 weeks
Immunogenicity
Time frame: Regular assessments from study start up to 26 weeks
Results and safety
The study was stopped early (reason given: Portfolio prioritization due to slow enrollment and variable spectrum of potential complement abnormalities in DDD patients.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2014.
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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.
Carla Nester, MD, MSA principal investigator
University of Iowa
Richard Smith, MD principal investigator
University of Iowa
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 CDX-1135 in people with Dense Deposit Disease and Membranoproliferative Glomerulonephritis Type II, run by Celldex Therapeutics 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 15 inclusion and 13 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 2014. 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 was stopped early (reason given: Portfolio prioritization due to slow enrollment and variable spectrum of potential complement abnormalities in DDD patients.). 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?
Safety (time frame: From first study drug dose for up to 26 weeks). The study lists 2 primary outcomes in all. 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 2014.