Pre-eclampsiaPhase 2NCT01566630
Safety and Efficacy of RLX030 in Pregnant Women With Pre- Eclampsia
A Phase 2 study testing RLX030 in people with Pre-eclampsia, run by Novartis Pharmaceuticals at 5 sites in 2 countries.
Trial summary
This study is designed in two parts. Part 1 will assess the safety and tolerability of different doses of RLX030 when given to pregnant women with pre- eclampsia (elevated blood pressure with protein in urine). Part 2 will assess whether an optimal dose of RLX030 can prolong pregnancy in women with pre-eclampsia. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women only
- Conditions the study is for
- Pre-eclampsia
- What is being tested?
- RLX030
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 3 participants
- Where
- 5 sitesin 2 countries
- Study dates
- May 2013to Aug 2014
- Phase
- Phase 2
- 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 18 to 40 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Written informed consent was obtained before any assessment was performed.
- Women at 18 to 40 years of age with a pregnancy 28 weeks (0 days) and 33 weeks (+4 days) gestational age. Gestational age was based on mother's last menstruation; if last menstruation was unknown, an alternative method was used as applicable and was documented in the (electronic) Case Report/Record Form [(e)CRF].
- Women with a diagnosis of pre-eclampsia or superimposed pre-eclampsia requiring hospitalization. Pre-eclampsia was defined as new onset of hypertension (SBP ≥ 140 or DBP ≥ 90 mmHg) or gestational hypertension accompanied by proteinuria (>= 0.3 g/24h) after 20 weeks of gestation. Superimposed pre-eclampsia was defined as chronic hypertension with new onset of proteinuria after 20 weeks of gestation.
- Reassuring fetal testing (cardiotocography and biophysical profile)
Who cannot join
- Severe hypertension (SBP ≥ 160 mmHg or DBP ≥ 110 mmHg) and /or those receiving anti-hypertensive treatment at time of randomization.
- Clinically relevant electrocardiogram (ECG) abnormalities at screening excluding those abnormalities commonly seen in pregnancy according to the Investigator.
- Symptoms indicative of severe pre-eclampsia or HELLP syndrome (Hemolysis, Elevated Liver enzymes, and Low Platelet count) for which immediate delivery of the baby may be indicated. Symptoms include persistent CNS symptoms (severe headaches, visual changes, altered mentation), persistent right upper quadrant or epigastric pain, nausea or vomiting, severe thrombocytopenia (<100,000/mm3) and abnormal (> 2X upper limit of normal) liver enzymes (alanine aminotransferase [ALT] or aspartate aminotransferase [AST]).
- Eclampsia during current pregnancy, vaginal bleeding present at screening, abruptio placentae, oligohydramnios
- Current diagnosis of a seizure disorder that requires chronic medication.
- Pre-gestational diabetes (Type 1 or Type 2) with or without diabetic retinopathy. Diagnosis (previous or current) of gestational diabetes, regardless of treatment, was allowed
- Known allergy to magnesium sulfate or steroids.
- Multifetal gestation, known major fetal anomaly, intrauterine growth restriction (<5th percentile).
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
United States4 sites
Novartis Investigative Site
Galveston, Texas, 77555-0587
Novartis Investigative Site
Lexington, Kentucky, 40503
Novartis Investigative Site
Louisville, Kentucky, 40202
Novartis Investigative Site
Mobile, Alabama, 36604
About this study
Official title: An Adaptive Multicentre, Randomized, Partially Double-blind, Placebo-controlled Study to Assess the Safety, PK and PD/Efficacy of RLX030 in Women With Pre-eclampsia
This study is designed in two parts. Part 1 will assess the safety and tolerability of different doses of RLX030 when given to pregnant women with pre- eclampsia (elevated blood pressure with protein in urine). Part 2 will assess whether an optimal dose of RLX030 can prolong pregnancy in women with pre-eclampsia.
- Conditions
- Pre-eclampsia
- Being tested
- Placebo, RLX030
- Keywords
- human recombinant RLX030, Pre-eclampsia, hemodynamics, Pharmacokinetics
- Medical subject headings
- Pre-Eclampsia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Placebo to RLX030 as intravenous infusion for 72 hours
RLX030Drug
RLX030 1 mg/mL vials
| Study group | Role | What they receive |
|---|---|---|
| RLX030 | Experimental | In part 1, within each cohort, two (2) patients per cohort will be treated open label with RLX030 and two (2) patients will be treated double blind with RLX030 as intravenous infusion for 72 hours. There will be 3 cohorts in part 1 with different doses of RLX030.
In part 2, there is no open label treatment on RLX030. In part 2, patients will be randomized in a double-blind fashion to this arm with the optimal dose of RLX030 as intravenous infusion for 72 hours as determined from part 1. Receives: Drug: RLX030 |
| Placebo | Placebo comparator | In part 1, equal number of subjects will be treated with matching placebo of RLX030 as intravenous infusion for 72 hours in 3 cohorts.
In part 2, patients will be treated with matching placebo of RLX030 as intravenous infusion for 72 hours Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients With Adverse Events, Serious Adverse and Death During Part 1 of the Study
Safety and tolerability was assessed by adverse events/serious adverse event and death monitoring.
Measured: Prior to delivery until 4-6 weeks post partum (maximum of 8 weeks)
Change From Baseline in Maternal Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Part 1of the Study (Part 1)
Maternal safety assessment to monitor pre-eclampsia by checking blood pressure during 72 hour treatment period as well as post-dose.
Measured: From baseline to during treatment period of a maximum 72 hours infusion prior to delivery until 4-6 weeks post partum in part 1 (maximum of 8 weeks)
Change From Baseline in Mean Maternal Arterial Pressure (Part 1)
Maternal safety assessment to monitor pre-eclampsia by checking mean arterial pressure during 72 hour treatment period as well as post-dose.
Measured: From baseline to during treatment period of a maximum 72 hours infusion prior to delivery until 4-6 weeks post partum in part 1 (maximum of 8 weeks)
Change From Baseline on Maternal Proteinuria (Part 1)
Pre-eclampsia was monitored by checking levels of protein in urine and by urinary protein/creatinine ratio (UPCR)
Measured: From baseline to during treatment period of a maximum 72 hours infusion prior to delivery until 4-6 weeks post partum in part 1 (maximum of 8 weeks)
Decrease in Utero-placental Blood Flow (Part 1)
Blood flow to the fetus was monitored using via a Doppler.
Measured: During treatment period of a maximum 72 hours infusion prior to delivery and up to delivery in part 1 (maximum of 3 weeks)
Change in Fetal Heart Rate (Part 1)
Heart rate of fetus was monitored continuously throughout 72 hour treatment period using a cardiotocograph.
Measured: During treatment period of a maximum 72 hours infusion prior to delivery and up to delivery in part 1 (maximum of 3 weeks)
Improvement in Renal Function Assessed by Increase in Creatinine Clearance
Measured: From randomization until 4-6 weeks post partum (maximum 8 weeks)
Rate of Spontaneous Delivery and/or Mode of Delivery
Measured: From randomization to delivery (maximum of 3 weeks)
Number of Patients With Absence of Anti-serelaxin Antibodies
Measured: From Randomization until 4-6 weeks post partum (maximum of 8 weeks)
Number of Patients With Abnormalities in Birth Weight, Gestational Age, Appearance, Pulse, Grimace, Activity, Respiration (APGAR) Score, Umbilical Cord Gases, and Days in Neonatal Intensive Care Unit (NICU)
Measured: up to 4 - 6 weeks post partum (maximum of 8 weeks )
Number of Patients With Abnormalities in Fetal Cardiotocography and Biophysical Profile
Measured: Randomization to delivery (maximum of 3 weeks)
Pharmacokinetics of RLX030: Area Under the Blood Concentration-time Curve From Time Zero to Infinity (AUCinf)-Part 1
Blood concentrations of RLX-030 was assayed to determine this PK parameter.
Measured: Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1
Pharmacokinetics of RLX030: Area Under the Blood Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast)-Part 1
Blood concentrations of RLX-030 was assayed to determine this PK parameter.
Measured: Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1
Pharmacokinetics of RLX030: Blood Concentration at 24 Hour (C 0-24h) After Administration- Part 1
Blood concentrations of RLX-030 was assayed to determine this PK parameter.
Measured: Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1
Pharmacokinetics of RLX030: Terminal Elimination Half-life (T1/2)- Part 1
Blood concentrations of RLX-030 was assayed to determine this PK parameter.
Measured: Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1
Pharmacokinetics of RLX030: Mean Residence Time (MRT)
Blood concentrations of RLX-030 was assayed to determine this PK parameter.
Measured: Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1
Secondary outcomes (1)
Mean Number of Days Before Delivery
Measured: From randomization until delivery (maximum of 3 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2012 (estimated)
- Study startMay 2013
- Primary completionAug 2014
- Study completionAug 2014
Why it stopped: Novartis terminated this study due to internal, strategic decisions.
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.
- Other trials for Pre-eclampsiaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01566630
- Sponsor's protocol ID
- CRLX030A2205
- Other IDs
- 2011-001617-14
- Status last verified
- Oct 2015
- First submitted
- 27 Mar 2012
- Last updated
- 5 Nov 2015
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Adaptive Multicentre, Randomized, Partially Double-blind, Placebo-controlled Study to Assess the Safety, PK and PD/Efficacy of RLX030 in Women With Pre-eclampsia
- ClinicalTrials.gov ID
- NCT01566630
- Acronym / sponsor ID
- CRLX030A2205
- Conditions
- Pre-eclampsia
- Keywords
- human recombinant RLX030, Pre-eclampsia, hemodynamics, Pharmacokinetics
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Novartis terminated this study due to internal, strategic decisions.
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- May 2013
- Primary completion
- Aug 2014 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 29 Mar 2012 (estimated)
- Results
- Posted 5 Nov 2015
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 designed in two parts. Part 1 will assess the safety and tolerability of different doses of RLX030 when given to pregnant women with pre- eclampsia (elevated blood pressure with protein in urine). Part 2 will assess whether an optimal dose of RLX030 can prolong pregnancy in women with pre-eclampsia.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| RLX030 | Experimental | Drug: RLX030In part 1, within each cohort, two (2) patients per cohort will be treated open label with RLX030 and two (2) patients will be treated double blind with RLX030 as intravenous infusion for 72 hours. There will be 3 cohorts in part 1 with different doses of RLX030. In part 2, there is no open label treatment on RLX030. In part 2, patients will be randomized in a double-blind fashion to this arm with the optimal dose of RLX030 as intravenous infusion for 72 hours as determined from part 1. |
| Placebo | Placebo comparator | Drug: PlaceboIn part 1, equal number of subjects will be treated with matching placebo of RLX030 as intravenous infusion for 72 hours in 3 cohorts. In part 2, patients will be treated with matching placebo of RLX030 as intravenous infusion for 72 hours |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Written informed consent was obtained before any assessment was performed.
- Women at 18 to 40 years of age with a pregnancy 28 weeks (0 days) and 33 weeks (+4 days) gestational age. Gestational age was based on mother's last menstruation; if last menstruation was unknown, an alternative method was used as applicable and was documented in the (electronic) Case Report/Record Form [(e)CRF].
- Women with a diagnosis of pre-eclampsia or superimposed pre-eclampsia requiring hospitalization. Pre-eclampsia was defined as new onset of hypertension (SBP ≥ 140 or DBP ≥ 90 mmHg) or gestational hypertension accompanied by proteinuria (>= 0.3 g/24h) after 20 weeks of gestation. Superimposed pre-eclampsia was defined as chronic hypertension with new onset of proteinuria after 20 weeks of gestation.
- Reassuring fetal testing (cardiotocography and biophysical profile)
Key exclusion criteria (8 listed)
- Severe hypertension (SBP ≥ 160 mmHg or DBP ≥ 110 mmHg) and /or those receiving anti-hypertensive treatment at time of randomization.
- Clinically relevant electrocardiogram (ECG) abnormalities at screening excluding those abnormalities commonly seen in pregnancy according to the Investigator.
- Symptoms indicative of severe pre-eclampsia or HELLP syndrome (Hemolysis, Elevated Liver enzymes, and Low Platelet count) for which immediate delivery of the baby may be indicated. Symptoms include persistent CNS symptoms (severe headaches, visual changes, altered mentation), persistent right upper quadrant or epigastric pain, nausea or vomiting, severe thrombocytopenia (<100,000/mm3) and abnormal (> 2X upper limit of normal) liver enzymes (alanine aminotransferase [ALT] or aspartate aminotransferase [AST]).
- Eclampsia during current pregnancy, vaginal bleeding present at screening, abruptio placentae, oligohydramnios
- Current diagnosis of a seizure disorder that requires chronic 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 |
|---|---|---|
| PlaceboPlacebo to RLX030 as intravenous infusion for 72 hours | Drug | Placebo |
| RLX030RLX030 1 mg/mL vials | Drug | RLX030 |
Primary outcome
Number of Patients With Adverse Events, Serious Adverse and Death During Part 1 of the Study
Time frame: Prior to delivery until 4-6 weeks post partum (maximum of 8 weeks)
Safety and tolerability was assessed by adverse events/serious adverse event and death monitoring.
Change From Baseline in Maternal Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Part 1of the Study (Part 1)
Time frame: From baseline to during treatment period of a maximum 72 hours infusion prior to delivery until 4-6 weeks post partum in part 1 (maximum of 8 weeks)
Maternal safety assessment to monitor pre-eclampsia by checking blood pressure during 72 hour treatment period as well as post-dose.
Change From Baseline in Mean Maternal Arterial Pressure (Part 1)
Time frame: From baseline to during treatment period of a maximum 72 hours infusion prior to delivery until 4-6 weeks post partum in part 1 (maximum of 8 weeks)
Maternal safety assessment to monitor pre-eclampsia by checking mean arterial pressure during 72 hour treatment period as well as post-dose.
Change From Baseline on Maternal Proteinuria (Part 1)
Time frame: From baseline to during treatment period of a maximum 72 hours infusion prior to delivery until 4-6 weeks post partum in part 1 (maximum of 8 weeks)
Pre-eclampsia was monitored by checking levels of protein in urine and by urinary protein/creatinine ratio (UPCR)
Decrease in Utero-placental Blood Flow (Part 1)
Time frame: During treatment period of a maximum 72 hours infusion prior to delivery and up to delivery in part 1 (maximum of 3 weeks)
Blood flow to the fetus was monitored using via a Doppler.
Change in Fetal Heart Rate (Part 1)
Time frame: During treatment period of a maximum 72 hours infusion prior to delivery and up to delivery in part 1 (maximum of 3 weeks)
Heart rate of fetus was monitored continuously throughout 72 hour treatment period using a cardiotocograph.
Improvement in Renal Function Assessed by Increase in Creatinine Clearance
Time frame: From randomization until 4-6 weeks post partum (maximum 8 weeks)
Rate of Spontaneous Delivery and/or Mode of Delivery
Time frame: From randomization to delivery (maximum of 3 weeks)
Number of Patients With Absence of Anti-serelaxin Antibodies
Time frame: From Randomization until 4-6 weeks post partum (maximum of 8 weeks)
Number of Patients With Abnormalities in Birth Weight, Gestational Age, Appearance, Pulse, Grimace, Activity, Respiration (APGAR) Score, Umbilical Cord Gases, and Days in Neonatal Intensive Care Unit (NICU)
Time frame: up to 4 - 6 weeks post partum (maximum of 8 weeks )
Number of Patients With Abnormalities in Fetal Cardiotocography and Biophysical Profile
Time frame: Randomization to delivery (maximum of 3 weeks)
Pharmacokinetics of RLX030: Area Under the Blood Concentration-time Curve From Time Zero to Infinity (AUCinf)-Part 1
Time frame: Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1
Blood concentrations of RLX-030 was assayed to determine this PK parameter.
Pharmacokinetics of RLX030: Area Under the Blood Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast)-Part 1
Time frame: Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1
Blood concentrations of RLX-030 was assayed to determine this PK parameter.
Pharmacokinetics of RLX030: Blood Concentration at 24 Hour (C 0-24h) After Administration- Part 1
Time frame: Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1
Blood concentrations of RLX-030 was assayed to determine this PK parameter.
Pharmacokinetics of RLX030: Terminal Elimination Half-life (T1/2)- Part 1
Time frame: Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1
Blood concentrations of RLX-030 was assayed to determine this PK parameter.
Pharmacokinetics of RLX030: Mean Residence Time (MRT)
Time frame: Baseline, 2, 6, 24,48,72, 76, 80 and 90 hours after initiation of infusion during part 1
Blood concentrations of RLX-030 was assayed to determine this PK parameter.
1 secondary outcome
Mean Number of Days Before Delivery
Time frame: From randomization until delivery (maximum of 3 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Pre-eclampsia
Recruiting
Exercise to Improve Heart and Metabolic Health After Childbirth in Women at High Risk for Preeclampsia
Postpartum Exercise, Cardiometabolic Health
RecruitingObservational study
Molecular Study of the Maternal-fetal Interface in Preeclampsia.
Preeclampsia
Active, not recruitingObservational study
The CoPenHagen PREeClampsia and cardIOvascUlar diSease Study
Pre-Eclampsia, Atherosclerosis
RecruitingObservational study
Estimated Risk of Preeclampsia in the First Trimester and Its Association With Subclinical Atherosclerosis and Cardiovascular Risk in Women With Type 1 Diabetes
Type 1 Diabetes, Preeclampsia
Not yet recruitingPhase 2
Furosemide vs Placebo in Severe Preeclampsia Postpartum
Severe Preeclampsia
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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing RLX030 in people with Pre-eclampsia, run by Novartis Pharmaceuticals at 5 sites in 2 countries.
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 4 inclusion and 8 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 5 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States, Italy. 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. 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 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?
Yes. Results are posted in the registry (first posted 5 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?
Number of Patients With Adverse Events, Serious Adverse and Death During Part 1 of the Study (time frame: Prior to delivery until 4-6 weeks post partum (maximum of 8 weeks)). The study lists 16 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 5 Nov 2015.