Intranasal Heparin Tolerability Study

NCT04490239 | Completed Early Phase 1 Results FDA Drug

• 1 other identifier: Intranasal Heparin
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators are investigating the tolerability of Heparin Sodium (porcine) administered topically via a nasal spray. This agent is being investigated as a potential prophylactic treatment to prevent infection by SARS(severe acute respiratory syndrome)-CoV-2, the novel coronavirus that causes COVID-19. Heparin Sodium (porcine) is an FDA-approved anticoagulant drug administered by injection. Recent work from multiple groups have found that heparin can prevent the infection of cells by SARS-CoV-2, indicating a possible use as a topical anti-viral. Numerous studies in both rodent models and humans have shown that heparin administered via a pulmonary or intranasal route enters the blood stream in negligible amounts, suggesting intranasal administration of heparin should be safe even at very large doses. Data from mouse models indicate that repeated daily nasal administration of heparin had no adverse effects in mice over a two week period (including weight loss, nose bleeds, loss of sense of smell, nasal discharge, or decreased blood clotting time). However, no data of repeated nasal administration of heparin in humans is available. The investigators will test nasal administration of FDA-approved heparin sodium (porcine), originally formulated for injection. The formulations the investigators will be testing consist of heparin, sodium chloride, and 1% benzyl alcohol as a preservative bottled in a nasal sprayer dispensing 0.1 mL(millilitres) per spray. The investigation is planned in two phases. A single-dose phase will test the acute tolerability of the drug. In this phase, subjects will be administered 0.1 mL of Heparin Sodium in each nostril formulated at one of two doses: Day 1 will test a formulation of 5000 U(units)/mL, and Day 2 will test a formulation of 10000 U(units) /mL. After each dose, subjects will be tested for systemic exposure via blood aPTT tests and platelet count, as well as for local topical toxicity via examination for epistaxis and anosmia, along with any other adverse events. In the chronic phase, subjects will be administered the highest dose that was tolerated in the acute phase daily for fourteen days. Subjects will be tested for aPTT and platelet count, as well as epistaxis, anosmia and any other adverse events.

Conditions

Covid19

Outcome Measures

Primary Outcomes (8)

• Number of Participants With Normal or Abnormal Activated Partial Thromboplastin Time (aPTT), Acute Phase Day 1

  A measurement of blood clotting ability; tests for systemic bioavailability of intranasal heparin collected 24 hours after a 1000 U intranasal dose of heparin

  24 hours after a 1000 U intranasal dose of heparin

• Number of Participants With Normal or Abnormal Activated Partial Thromboplastin Time (aPTT), Acute Phase Day 2

  A measurement of blood clotting ability; tests for systemic bioavailability of intranasal heparin collected 24 hours after a 2000 U intranasal dose of heparin

  24 hours after 2000 U dose intranasal heparin

• Number of Participants With Normal or Abnormal Activated Partial Thromboplastin Time (aPTT), Chronic Phase Day 14

  A measurement of blood clotting ability; tests for systemic bioavailability of intranasal heparin obtained immediately after the 14 consecutive day of daily 2000 U dose of intranasal heparin

  Day 14, chronic phase

• Number of Participants With Normal or Abnormal Activated Partial Thromboplastin Time (aPTT), Chronic Phase Day 15

  A measurement of blood clotting ability; tests for systemic bioavailability of intranasal heparin obtained 24 hours after the 14 consecutive day of daily 2000 U dose of intranasal heparin

  24 hours after the last 2000 U dose of the chronic phase

• Percent Change in Platelet Count From Pre-dose Baseline

  Indicative of heparin-induced thrombocytopenia, a serious adverse side effect of systemically bioavailable heparin, measured immediately after the last 2000 U intranasal dose of the chronic phase.

  Pre-dose baseline, Day 14 chronic phase

• Number of Incidents of Epistaxis, Acute Phase

  Number of incidents of blood coming from the nose during the acute phase

  Day 0 through Day 2, acute phase

• Number of Incidents of Epistaxis, Chronic Phase

  Blood coming from the nose or pink tinged nasal secretions

  Day 1 through Day 15, chronic phase

• Number of Participants With Normal or Abnormal Platelet Counts, Chronic Phase Day 14

  Abnormally low platelet counts indicative of heparin-induced thrombocytopenia, a serious adverse side effect of systemically bioavailable heparin, measured immediately after the last 2000 U intranasal dose of the chronic phase.

  Day 14, Chronic Phase

Secondary Outcomes (2)

• Other Adverse Effects, Acute Phase

  Day 0 through Day 2, acute phase

• Other Adverse Effects, Chronic Phase

  Day 1 through Day 15, chronic phase

Study Arms (1)

Experimental Arm

EXPERIMENTAL

Subjects will be administered heparin sodium (porcine) bottled in a nasal sprayer with a volume per spray of 0.1 mL. Acute phase: On day 1, each subject will be administered 0.1 mL per nostril of 5000 U/mL heparin sodium (porcine), for a total dose of 1000 U. Vital signs, blood work, and follow-up clinical observation will be used to detect adverse effects. On day 2, each subject will be administered 0.1 mL per nostril of 10000 U/mL heparin sodium (porcine), for a total dose of 2000 U. Vital signs, blood work, and follow-up clinical observation will be used to detect adverse effects. Chronic phase: The highest acute dose that has no impact on aPTT or INR will be used for the chronic phase of this study. Each subject will be administered a daily dose for fourteen days. The first and last dose will be administered in the clinic; all other doses will be self-administered by subjects at home at the same time of day using a dosing diary to keep records.

Drug: Intranasal heparin sodium (porcine)

Interventions

Intranasal heparin sodium (porcine) DRUG

Intranasal heparin sodium

Also known as: NDC (National Drug Code) 0409-2721-30, NDC 0409-2723-01

Experimental Arm

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Normal, healthy adults aged 18 to 65 years

You may not qualify if:

• Allergy to Heparin
• Currently taking any prescription blood thinners or anti-coagulants, or currently taking any intranasal medication
• Known history of anemia, thrombocytopenia, or other blood disorder
• Autoimmune disorders
• Known history of Neurologic/Psychiatric disorders
• Report of an active infection
• Subject is pregnant or breast-feeding, or is expecting to conceive during the study.
• NOTE: Subjects will be instructed to abstain from alcohol for the duration of the study.

Sponsors & Collaborators

• Joshua Sharp: lead

Study Sites (1)

The University of Mississippi National Center for Natural Products Research

University, Mississippi, 38677-1848, United States

Location

Related Publications (1)

• Tandon R, Sharp JS, Zhang F, Pomin VH, Ashpole NM, Mitra D, Jin W, Liu H, Sharma P, Linhardt RJ. Effective Inhibition of SARS-CoV-2 Entry by Heparin and Enoxaparin Derivatives. bioRxiv [Preprint]. 2020 Jul 28:2020.06.08.140236. doi: 10.1101/2020.06.08.140236.

  PMID: 32577638 BACKGROUND

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Dr. Joshua Sharp
• Organization: University of Mississippi

jsharp@olemiss.edu

662-915-1758

Study Officials

• Bill Gurley, PhD

  University of Mississippi Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Model Details: This study will evaluate the acute and multi-day (14 days) tolerability of intranasally administered heparin. Two doses will be tested in the acute phase: 1000 U/day, then 2000 U/day. In the multi-day phase, the highest tolerated dose from the acute phase will be tested over a 14-day period of daily self-administration.

Study Record Dates

• First Submitted: July 20, 2020
• First Posted: July 29, 2020
• Study Start: October 9, 2020
• Primary Completion: November 18, 2020
• Study Completion: November 18, 2020
• Last Updated: April 30, 2021
• Results First Posted: April 28, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Beginning 3 months and ending 36 months following publication
• Access Criteria: Proposals should be directed to jsharp@olemiss.edu. To gain access, requestors will need to sign a data access agreement.

Locations

US (1)