Subcutaneous Elafin in Healthy Subjects

NCT03522935 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 42336P01HL108797
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Pulmonary Arterial Hypertension

Outcome Measures

Primary Outcomes (1)

• 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.

  28 day time period

Secondary Outcomes (1)

• Pharmacokinetic/pharmacodynamic (PK/PD) and immunogenicity parameters in blood sample: AUC0-last

  28 day time period

Other Outcomes (7)

• Pharmacokinetic/pharmacodynamic (PK/PD) and immunogenicity parameters in blood sample: Cmax

  28 day time period

• Pharmacokinetic/pharmacodynamic (PK/PD) and immunogenicity parameters in blood sample: Tmax

  28 day time period

• Pharmacokinetic/pharmacodynamic (PK/PD) and immunogenicity parameters in blood sample: Ke

  28 day time period

Study Arms (6)

Elafin 0.03 mg/kg

EXPERIMENTAL

5 subjects will be administered with 0.03 mg/kg of Elafin subcutaneously once daily for 7 days.

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.

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.

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.

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.

Drug: Elafin

Placebo Drug

PLACEBO COMPARATOR

5 subjects will be administered with placebo drug subcutaneously once daily for 7 days.

Drug: Placebo

Interventions

Elafin DRUG

Elafin subcutaneous.

Also known as: Tiprelestat

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

Placebo DRUG

Placebo subcutaneous.

Placebo Drug

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)
• 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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You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Roham T. Zamanian: lead
• Duke University: collaborator
• SRI International: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Duke Early Phase Research Unit (DEPRU)

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

Elafin

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Proteinase Inhibitory Proteins, Secretory; Peptides; Amino Acids, Peptides, and Proteins; Proteins

Study Officials

• Roham T Zamanian, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: February 1, 2018
• First Posted: May 14, 2018
• Study Start: March 18, 2019
• Primary Completion: October 25, 2019
• Study Completion: November 18, 2020
• Last Updated: August 15, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)