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CompletedNCT03287635Updated Jan 28, 2021Results posted

Clinical Efficacy of H.P. Acthar Gel 80 U/ml to Improve the Signs and Symptoms in Subjects With Dry Eye Disease

A Phase 4 interventional study of Corticotropin 80Unit/Ml Repository Injection in Dry Eye Disease, sponsored by Toyos Clinic. Completed at 1 site in United States. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-01-28.

Sponsored by Toyos Clinic · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
19
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

Study Title: A Phase 4 Study to Assess the Clinical Efficacy of H.P. Acthar Gel 80 U/ml to Improve the Signs and Symptoms in Subjects with Dry Eye Disease

Read the detailed description

Objectives: The primary objective of this study is to investigate the safety and efficacy of H.P. Acthar Gel 80 U/ml in subjects with a documented clinical diagnosis of dry eye disease.

Study Population: The study population will consist of subjects diagnosed with dry eye disease.

Number of Subjects: Approximately 12 subjects

Investigational Product: H.P. Acthar Gel 80 U/ml sufficient for the duration of the study will be supplied by Mallinkrodt to the enrolled subjects

Route and Duration of Administration: Product will be injected subcutaneously weekly by subjects for approximately 12 weeks.

Study Design: This is a Phase 4, single center single arm study designed to evaluate the safety and efficacy of H.P. Achthar Gel in subjects with dry eye disease.

Approximately 25 subjects will be screened and 12 subjects enrolled at one center in the United States.

Subjects will be given 80 international units of study medication subcutaneously depending on the severity of the disease as determined by the primary investigator.

The study will include 3 study visits over 12 weeks. At Visit 1 Screening (14 +/- 1 days prior to Day 1), subjects meeting inclusion/exclusion criteria will begin investigational drug use. Subjects will return for evaluations at Visit 2 (Day 42+/-3 days) and Visit 3 (Day 84 +/-5 days). Subjects will be released from the study at the end of Visit 3 (Day 84+/- 5 days.)

02

Conditions studied

03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  • At Visit 1 (Screening) individuals of either gender or race will be eligible for study participation if they

    1. Provide written informed consent and HIPAA authorization prior to any study related procedures
    2. Are 18 years of age or older
    3. Are willing and able to follow instructions and can be present for required study visits.
    4. Have documented clinical diagnosis of dry eye disease in one or both eyes.
    5. Have a score of at least 40mm on the ocular discomfort scale
    6. Have at least 5 spk on one or both corneas
    7. Have a grade of 1 or greater in the nasal or temporal areas of one or both eyes.
    8. Have normal lid anatomy.
    9. Are women of child bearing potential who are not pregnant or lactating and who are either abstinent and willing to remain so for the course of the trial or have an IUD in place for at least 3 months prior and through Visit 4, barrier method with spermicide for at least 3 months prior and through Visit 4, stable hormonal contraceptive for at least 3 months prior and through Visit 4 or in a monogamous relationship with a surgically sterilized (vasectomized) partner at least 6 months prior to Visit 1 and through the course of the trial.
    10. Are postmenopausal (no menstrual cycle for at least one year prior to Visit 1) or have undergone bilateral tubal ligation, hysterectomy, hysterectomy with uni or bilateral oophorectomy, or bilateral oophorectomy.

Exclusion criteria

Exclusion Criteria:

In order for subjects to be eligible for the study

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  1. Have a known hypersensitivity or contraindication to the investigational product or their components.
  2. Have used any of the following medications within 14 days prior to screening

    a. Topical or nasal vasoconstrictors

  3. Subjects can be on the following medications if they have been on a stable dose for 12 weeks topical cyclosporine, topical lifitegrast and/or topical loteprednol etabonate. Tetracycline compounds, omega 3s, anticholinergics, anticonvulsants, antidepressants, retinoids, systemic immunosuppressive agents including oral corticosteroids, non-steroidals, antihistamines or mast cell stabilizers, punctal plugs, contact lens wear and glaucoma medications.
  4. Subjects must be unwilling to abstain from eyelash growth medications for the duration of the trial.
  5. Subjects must not have had penetrating intraocular surgery, refractive surgery or corneal transplantation, eyelid surgery within 12 weeks prior to Visit 1.
  6. Subjects with a history of herpetic keratitis.
  7. Have serious or severe disease or uncontrolled medical condition that in the judgement of the investigator could confound study assessments or limit compliance.
04

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
19 participants (actual)

Study arms

  • Experimental
    Acthar gel 80 U/ml

    Patients who continue to experience clinically significant symptoms of dry eye disease even after utilizing traditional methods of treatment for dry eye including but not limited to artificial tears, warm compresses, topical anti-inflammatories like cyclosporine and/or lifitegrast. Patients will receive repository corticotropin intramuscular injections 80 u/ml 2-3 times weekly for up to 3 months as judged by the investigator.

    Drug: Corticotropin 80Unit/Ml Repository Injection

Interventions

  • DrugCorticotropin 80Unit/Ml Repository Injection

    H.P. Acthar Gel (repository corticotropin injection) is an adrenocorticotropic hormone (ACTH) analogue used for: Treatment during an exacerbation or as maintenance therapy in selected cases of systemic lupus erythematosus.

    Also known as: H.P. Acthar gel

05

What researchers measure

Primary outcomes

  1. Dry Eye Comfort Questionnaire, SANDE

    Subjects will be asked to subjectively rate their eye dryness at Visit 1,2 and 3. Subjects will be instructed to rate eye dryness using the scale below. The total length of the line from "no dryness" to "maximal dryness" is 100 mm. The length of the line between the "no dryness" starting point and the first point at which the subject mark crosses the line will be measured in mm. This assessment is a general assessment of the change of both eyes of dryness measure from baseline to final study visit. The measure of discomfort was for the instantaneous measurement at the time of the specific visit.

    Time frame: 12 weeks total. Measure is change on SANDE scale (0 is no dryness and 100mm is maximal dryness) from baseline to final value. Higher values reflect greater amounts of subjective dryness.

  2. 1. Conjunctival Staining With Lissamine Green

    Change in Conjunctival staining with lissamine green.

    Time frame: 12 weeks total. Measure is change from baseline to final,

Secondary outcomes

  1. Intraocular Pressure

    goldmann tonometry used by qualified technician with fluorescein staining

    Time frame: 12 weeks measuring change from baseline to final

06

Results

Posted Jan 28, 2021
Limitations and caveats
single site, open label study

Participant flow

Participant flow — Overall Study
MilestoneActhar Gel 80 U/ml
Started19
Completed12
Not completed7
Withdrew: Lost to follow-up5
Withdrew: Withdrawal by subject1
Withdrew: Physician decision1

Outcome measures

PrimaryDry Eye Comfort Questionnaire, SANDE

Subjects will be asked to subjectively rate their eye dryness at Visit 1,2 and 3. Subjects will be instructed to rate eye dryness using the scale below. The total length of the line from "no dryness" to "maximal dryness" is 100 mm. The length of the line between the "no dryness" starting point and the first point at which the subject mark crosses the line will be measured in mm. This assessment is a general assessment of the change of both eyes of dryness measure from baseline to final study visit. The measure of discomfort was for the instantaneous measurement at the time of the specific visit.

Time frame:
12 weeks total. Measure is change on SANDE scale (0 is no dryness and 100mm is maximal dryness) from baseline to final value. Higher values reflect greater amounts of subjective dryness.
Reported as:
Mean · scores on a scale
Dry Eye Comfort Questionnaire, SANDE
scores on a scaleActhar Gel 80 U/ml
Dry Eye Comfort Questionnaire, SANDE44.77 ± 3.13
Primary1. Conjunctival Staining With Lissamine Green

Change in Conjunctival staining with lissamine green.

Time frame:
12 weeks total. Measure is change from baseline to final,
Reported as:
Mean · staining spots on conjunctiva
1. Conjunctival Staining With Lissamine Green
staining spots on conjunctivaActhar Gel 80 U/ml
1. Conjunctival Staining With Lissamine Green-173.33 ± 464.59
SecondaryIntraocular Pressure

goldmann tonometry used by qualified technician with fluorescein staining

Time frame:
12 weeks measuring change from baseline to final
Reported as:
Mean · mm Hg
Intraocular Pressure
mm HgActhar Gel 80 U/ml
Intraocular Pressure-1.65 ± 1.4

Adverse events

Collected over 12 weeks. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Acthar Gel 80 U/ml0/19 (0%)0/19 (0%)1/19 (5.3%)
Most frequent other events
Most frequent other events
EventActhar Gel 80 U/ml
hypertensionCardiac disorders1/19

Baseline characteristics

Patients experience persistent symptomatic dry eye disease despite treatment with traditional therapies.

Age, Categorical
Age, Categorical(Participants)Acthar Gel 80 U/ml
<=18 years0
Between 18 and 65 years15
>=65 years4
Age, Continuous
Age, Continuous(years)Acthar Gel 80 U/ml
Mean54 (27 to 74)
Sex: Female, Male
Sex: Female, Male(Participants)Acthar Gel 80 U/ml
Female13
Male6
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Acthar Gel 80 U/ml
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American0
White19
More than one race0
Unknown or Not Reported0
Region of Enrollment
Region of Enrollment(Participants)Acthar Gel 80 U/ml
United States19
07

Study locations

1 site
  • Toyos Clinic
    Nashville, Tennessee 37203, United States
08

References and documents

Publications

  • Toyos M, Toyos R, Jodoin B, Bunch R. Results from a Prospective, Open-Label, Phase 4 Pilot Study of Repository Corticotropin Injection for Moderate and Severe Dry Eye Disease. Ophthalmol Ther. 2022 Jun;11(3):1231-1240. doi: 10.1007/s40123-022-00501-2. Epub 2022 Apr 23. PubMed 35460497 ↗

Study documents

  • Study protocol · May 10, 2018
  • Statistical analysis plan · May 10, 2018
  • Informed consent form · Oct 16, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Undecided

09

Registry details

Key details

Study ID
NCT03287635
Lead sponsor
Toyos Clinic
Collaborators
Mallinckrodt
Responsible party
Sponsor
First posted
Sep 19, 2017
Start date
Jul 1, 2018
Primary completion
Feb 1, 2020
Completion
Mar 4, 2020
Results posted
Jan 28, 2021
Last update
Jan 28, 2021

Study contacts

Melissa Toyos, MD
principal investigator · Toyos Clinic

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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