Pulmonary Arterial HypertensionPhase 1NCT03522935
Subcutaneous Elafin in Healthy Subjects
A Phase 1 study testing Elafin in people with Pulmonary Arterial Hypertension, run by Roham T. Zamanian at 1 site in United States.
Trial summary
A multiple-ascending-dose (MAD), randomized, placebo-controlled, blinded trial to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of Elafin in healthy adult subjects. The purpose of this study is to assess Elafin that is being developed for treatment of PAH. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- Elafin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Mar 2019to 18 Nov 2020
- 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 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- A subject will be eligible only if all of the following criteria apply:
- Male or female, 18 - 55 years of age
- No history or clinically relevant cardiovascular, renal, gastrointestinal, hepatic, metabolic, endocrine, neurological, or psychiatric abnormalities and is in general good health at screening examination.
- Normal or clinically acceptable ECG
- Normal blood pressure (systolic: 90 - 140 mmHg; diastolic: 50 - 90 mmHg) and heart rate (45 - 100 bpm)
- Body mass index of 18.0 - 32.0 (kg/m2)
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- Ability to communicate well with the investigator and to comply with the requirements of the entire study.
- Informed consent.
- Females of childbearing potential must use an acceptable form of contraception at time of enrollment (and throughout the duration of study) including, but not limited to the following:
- Documentation of surgical sterilization (bilateral tubal ligation, hysterectomy)
- Naturally postmenopausal (spontaneous cessation of menses) for at least 24 consecutive months prior to dosing on Day -1 and with an FSH level at screening of ≥ 40 mIU/mL
- Intrauterine Device (IUD) plus condom plus contraceptive sponge or foam or jelly
- Condom plus contraceptive sponge or foam or jelly
- Hormonal contraception (combination oral contraceptives, transdermal patch, injectables, implantables, or vaginal ring) *Subject is not of childbearing potential if the following criteria have been met:
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- Hysterectomy > 1 month ago
- Bilateral oophorectomy > 1 month ago
- 45-50 years old AND LMP ≥ 24 months ago and documented FSH > 40mIU/mL
- Males must agree to use a barrier method of birth control from 30 days before first study drug administration until 90 days after last study drug administration.
Who cannot join
- A subject will not be eligible if any of the following criteria apply:
- Administration of any investigational drug 45 days prior to study enrollment.
- Active participation in another interventional clinical trial.
- Use of any prescription medication within 30 days (with exception to oral contraceptives) or over-the-counter medication (OTC) within 7 days before first study drug administration. Use of OTC medications may be permitted after day 1 visit until end of study with approval of the protocol investigator.
- Subject performed heavy physical exertion 2 days before eligibility assessment and before admission into clinical research center.
- Subject consumes more than 500 mL of beer/day or 250 mL of wine/day or 2 glasses of liquor/day.
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- Subject has a history of chronic alcohol or drug abuse within the last 4 weeks.
- Subject smokes more than 10 cigarettes per day or has done so within 6 months prior to eligibility assessment.
- Subject has a diet that deviates notably from the "normal" amounts of protein, carbohydrate, and fat, as judged by the investigator (e.g., vegetarians or vegans).
- Subject consumes more than 600 mg of caffeine/day (200 mL of coffee contain approximately 100 mg of caffeine, 200 mL of black tea approximately 30 mg and 200 mL of soda approximately 20 mg).
- Subject has donated blood or had a comparable blood loss (>400 mL) within the last 3 months prior to eligibility assessment or anemia defined by hematocrit value less than 30% at screening.
- Subject has any clinically relevant abnormality in physical examination, vital signs and electrocardiogram (ECG).
- Serious adverse reaction or hypersensitivity to any drug.
- Inability to communicate or co-operate due to a language problem, poor mental development or impaired cerebral function.
- Females who are lactating or at risk of pregnancy.
- Presence of pain incurred by unknown causes.
- History of asthma or other respiratory disease.
- History of neurologic or neuromuscular disease.
- History of hypotension, hypertension or cardiovascular disease.
- History of gastrointestinal, hepatic, or renal disease and/or impairment.
- Positive urine drug screen for drugs with a high potential for abuse and low persistence in the urine.
- Subject with active or history of malignancy, known Hepatitis B or C, or HIV.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke Early Phase Research Unit (DEPRU)
Durham, North Carolina, 27710
About this study
Official title: Safety and Tolerability of Escalating Doses of Subcutaneous Elafin (Tiprelestat) Injection in Healthy Normal Subjects
A multiple-ascending-dose (MAD), randomized, placebo-controlled, blinded trial to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of Elafin in healthy adult subjects. The purpose of this study is to assess Elafin that is being developed for treatment of PAH. Elafin inhibits elastase, an enzyme that is increased in pulmonary hypertension and is a major factor in the development of PAH. Elafin will be administered subcutaneously daily for 7 days in normal healthy subjects followed over a 28 day time period.
Read the detailed description
There will be a total of up to 30 subjects randomly assigned to 5 groups with 6 subjects in each group. One subject in each group will be assigned to placebo drug and 5 subjects to active drug. Subjects in each group will receive a single daily dose of Elafin/Placebo for total of 7 days. There will be ascending doses across groups. Groups receiving a higher dose will only do so after the previous group has completed dosing (i.e., 7 days). Each subject will be followed over a 28 day time period.
An interim trial analysis will occur after completion of the 2nd cohort in order for the research team to review PK and safety data to determine modification (if needed) of dosing strategy for groups 3-5. The study is also designed to absorb a de-escalation strategy. If the protocol requires a lowering of dose from the initial dosing, a new group will be assigned a low-dose subcutaneous Elafin regimen.
The study will conclude at any dose that produces clinically significant adverse effects and identified as Maximum Tolerated Dose (MTD).
- Conditions
- Pulmonary Arterial Hypertension
- Being tested
- Elafin, Placebo
- Medical subject headings
- Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ElafinDrug
Also called Tiprelestat
Elafin subcutaneous.
PlaceboDrug
Placebo subcutaneous.
| Study group | Role | What they receive |
|---|---|---|
| Elafin 0.03 mg/kg | Experimental | 5 subjects will be administered with 0.03 mg/kg of Elafin subcutaneously once daily for 7 days. Receives: Drug: Elafin |
| Elafin 0.06 mg/kg | Experimental | 5 subjects will be administered with 0.06 mg/kg of Elafin subcutaneously once daily for 7 days. Receives: Drug: Elafin |
| Elafin 0.10 mg/kg | Experimental | 5 subjects will be administered with 0.10 mg/kg of Elafin subcutaneously once daily for 7 days. Receives: Drug: Elafin |
| Elafin 0.15 mg/kg | Experimental | 5 subjects will be administered with 0.15 mg/kg of Elafin subcutaneously once daily for 7 days. Receives: Drug: Elafin |
| Elafin 0.18 mg/kg | Experimental | 5 subjects will be administered with 0.18 mg/kg of Elafin subcutaneously once daily for 7 days. Receives: Drug: Elafin |
| Placebo Drug | Placebo comparator | 5 subjects will be administered with placebo drug subcutaneously once daily for 7 days. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events in healthy controls.
Safety and tolerability will be determined on the basis of adverse events reported and the severity of adverse events.
Measured: 28 day time period
Secondary outcomes (1)
Pharmacokinetic/pharmacodynamic (PK/PD) and immunogenicity parameters in blood sample: AUC0-last
AUC0-last: Area under the concentration time-curve to the last concentration above the lower limit of quantitation (after final dose consumed)
Measured: 28 day time period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2018
- Study start18 Mar 2019
- Primary completion25 Oct 2019
- Study completion18 Nov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Arterial HypertensionStudies 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
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Roham T. Zamanian
- Sponsor type
- University, hospital or other
- Collaborators
- Duke University, SRI International, National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor-investigator, Roham T. Zamanian, Stanford University
- Investigators
- Roham T Zamanian, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03522935
- Sponsor's protocol ID
- 42336
- Other IDs
- P01HL108797
- Status last verified
- Aug 2024
- First submitted
- 1 Feb 2018
- Last updated
- 15 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Tolerability of Escalating Doses of Subcutaneous Elafin (Tiprelestat) Injection in Healthy Normal Subjects
- ClinicalTrials.gov ID
- NCT03522935
- Acronym / sponsor ID
- 42336
- Conditions
- Pulmonary Arterial Hypertension
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Roham T. ZamanianUniversity, hospital or other
- Collaborators
- Duke University, SRI International, National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 18 Mar 2019 (actual)
- Primary completion
- 25 Oct 2019 (actual)
- Study completion
- 18 Nov 2020 (actual)
- First posted
- 14 May 2018 (actual)
- 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.
A multiple-ascending-dose (MAD), randomized, placebo-controlled, blinded trial to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of Elafin in healthy adult subjects. The purpose of this study is to assess Elafin that is being developed for treatment of PAH. Elafin inhibits elastase, an enzyme that is increased in pulmonary hypertension and is a major factor in the development of PAH. Elafin will be administered subcutaneously daily for 7 days in normal healthy subjects followed over a 28 day time period.
Detailed description
There will be a total of up to 30 subjects randomly assigned to 5 groups with 6 subjects in each group. One subject in each group will be assigned to placebo drug and 5 subjects to active drug. Subjects in each group will receive a single daily dose of Elafin/Placebo for total of 7 days. There will be ascending doses across groups. Groups receiving a higher dose will only do so after the previous group has completed dosing (i.e., 7 days). Each subject will be followed over a 28 day time period.
An interim trial analysis will occur after completion of the 2nd cohort in order for the research team to review PK and safety data to determine modification (if needed) of dosing strategy for groups 3-5. The study is also designed to absorb a de-escalation strategy. If the protocol requires a lowering of dose from the initial dosing, a new group will be assigned a low-dose subcutaneous Elafin regimen.
The study will conclude at any dose that produces clinically significant adverse effects and identified as Maximum Tolerated Dose (MTD).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, care provider)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Elafin 0.03 mg/kg | Experimental | Drug: Elafin5 subjects will be administered with 0.03 mg/kg of Elafin subcutaneously once daily for 7 days. |
| Elafin 0.06 mg/kg | Experimental | Drug: Elafin5 subjects will be administered with 0.06 mg/kg of Elafin subcutaneously once daily for 7 days. |
| Elafin 0.10 mg/kg | Experimental | Drug: Elafin5 subjects will be administered with 0.10 mg/kg of Elafin subcutaneously once daily for 7 days. |
| Elafin 0.15 mg/kg | Experimental | Drug: Elafin5 subjects will be administered with 0.15 mg/kg of Elafin subcutaneously once daily for 7 days. |
| Elafin 0.18 mg/kg | Experimental | Drug: Elafin5 subjects will be administered with 0.18 mg/kg of Elafin subcutaneously once daily for 7 days. |
| Placebo Drug | Placebo comparator | Drug: Placebo5 subjects will be administered with placebo drug subcutaneously once daily for 7 days. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (19 listed)
- Male or female, 18 - 55 years of age
- No history or clinically relevant cardiovascular, renal, gastrointestinal, hepatic, metabolic, endocrine, neurological, or psychiatric abnormalities and is in general good health at screening examination.
- Normal or clinically acceptable ECG
- Normal blood pressure (systolic: 90 - 140 mmHg; diastolic: 50 - 90 mmHg) and heart rate (45 - 100 bpm)
- Body mass index of 18.0 - 32.0 (kg/m2)
Key exclusion criteria (22 listed)
- Administration of any investigational drug 45 days prior to study enrollment.
- Active participation in another interventional clinical trial.
- Use of any prescription medication within 30 days (with exception to oral contraceptives) or over-the-counter medication (OTC) within 7 days before first study drug administration. Use of OTC medications may be permitted after day 1 visit until end of study with approval of the protocol investigator.
- Subject performed heavy physical exertion 2 days before eligibility assessment and before admission into clinical research center.
- Subject consumes more than 500 mL of beer/day or 250 mL of wine/day or 2 glasses of liquor/day.
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 |
|---|---|---|
| ElafinAlso: TiprelestatElafin subcutaneous. | Drug | Elafin 0.03 mg/kg, Elafin 0.06 mg/kg, Elafin 0.10 mg/kg, Elafin 0.15 mg/kg, Elafin 0.18 mg/kg |
| PlaceboPlacebo subcutaneous. | Drug | Placebo Drug |
Primary outcome
Incidence of Treatment-Emergent Adverse Events in healthy controls.
Time frame: 28 day time period
Safety and tolerability will be determined on the basis of adverse events reported and the severity of adverse events.
1 secondary outcome
Pharmacokinetic/pharmacodynamic (PK/PD) and immunogenicity parameters in blood sample: AUC0-last
Time frame: 28 day time period
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 15 Aug 2024.
- Individual participant dataSharing planned: No
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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.
Roham T Zamanian, MD principal investigator
Stanford University
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 Elafin in people with Pulmonary Arterial Hypertension, run by Roham T. Zamanian 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 19 inclusion and 22 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 15 Aug 2024. 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. 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 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 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.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Events in healthy controls. (time frame: 28 day time period). 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 15 Aug 2024; AzTrials last refreshed its copy on 6 Nov 2026.