Adrenocorticotropic Hormone (ACTH) for Post-op Inflammation in Proliferative Vitreoretinopathy (PVR)

NCT03727776 | Completed Early Phase 1 FDA Drug

• 1 other identifier: IRB00179012
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

This is a pilot study to measure levels of albumin and inflammatory cytokines \[including Transforming Growth Factor-Beta (TGF-β) and Interleukin-1 Beta (IL-1β)\] in the aqueous humor of post-operative proliferative vitreoretinopathy patients receiving subcutaneous injections of H.P. Acthar®, an adrenocorticotropic hormone (ACTH) analog. The study will be conducted at the Wilmer Eye Institute, Johns Hopkins Hospital. A total of 15 patients will be enrolled and randomized 2:1 to H.P. Acthar® or standard of care. Treatment duration will be 8 weeks and study duration will be 12 weeks. There will be a total of 7 study visits (baseline, day of surgery, post-operative day 1, week 1, week 4, week 8, and week 12). Subjects will self-administer subcutaneous injections of 80 units of H.P. Acthar® starting on post-operative day 1 for twice a week until week 8. Subjects in the control arm will be managed per the standard of care. Aqueous samples will be obtained at the onset of surgery, 1 day, 1 week and 8 weeks after surgery. Aqueous levels of albumin and inflammatory cytokines (including TGF-β and IL-1β) will be measured at each time point.

Conditions

Proliferative Vitreoretinopathy

Keywords

Post-operative Intraocular Inflammation

Outcome Measures

Primary Outcomes (3)

• Change in mean aqueous levels of albumin in post-operative PVR patients receiving subcutaneous injections of H.P. Acthar® versus controls

  The levels of albumin in the aqueous humor are indicative of blood-retinal barrier breakdown and will be measured in mg/dl

  Baseline, 1 day after surgery, 8 weeks after surgery

• Change in mean aqueous levels of TGF-B in post-operative PVR patients receiving subcutaneous injections of H.P. Acthar® versus controls

  The levels of TGF-B in the aqueous humor are indicative of intraocular inflammation and will be measured in mg/dl

  Baseline, 1 day after surgery, 8 weeks after surgery

• Change in mean aqueous levels of interleukin-1B (IL-1B) in post-operative PVR patients receiving subcutaneous injections of H.P. Acthar® versus controls

  The levels of IL-1B in the aqueous humor are indicative of intraocular inflammation and will be measured in mg/dl

  Baseline, 1 day after surgery, 8 weeks after surgery

Secondary Outcomes (8)

• Change in mean aqueous levels of albumin in post-operative PVR patients receiving subcutaneous injections of H.P. Acthar® versus controls

  Baseline, 1 day after surgery, 1 week after surgery

• Change in mean aqueous levels of TGF-B in post-operative PVR patients receiving subcutaneous injections of H.P. Acthar® versus controls

  Baseline, 1 day after surgery, 1 week after surgery

• Change in mean aqueous levels of interleukin-1B (IL-1B) in post-operative PVR patients receiving subcutaneous injections of H.P. Acthar® versus controls

  Baseline, 1 day after surgery, 1 week after surgery

• Change in mean grade of aqueous cell in post-operative PVR patients receiving subcutaneous injections of H.P. Acthar® versus controls

  1 week, 4 weeks, 8 weeks and 12 weeks after surgery

• Change in mean grade of flare in post-operative PVR patients receiving subcutaneous injections of H.P. Acthar® versus controls

  1 week, 4 weeks, 8 weeks and 12 weeks after surgery

Study Arms (2)

H.P. Acthar ®

EXPERIMENTAL

Subjects will self-administer subcutaneous injections of 80 units of adrenocorticotropic hormone analog starting on post-operative day 1 for twice a week until week 8.

Drug: Adrenocorticotropic Hormone

Controls

NO INTERVENTION

Subjects will be managed per the standard of care.

Interventions

Adrenocorticotropic Hormone DRUG

Adrenocorticotropic hormone (ACTH) is a melanocortin peptide hormone that is normally produced in the pituitary gland and acts as a major regulator of adrenal cortex function. It stimulates the adrenal cortex to produce and secrete glucocorticoids. ACTH is available for clinical usage as an injectable gel (H.P. Acthar®).

Also known as: H.P. Acthar Gel, Repository Corticotropin Injection

H.P. Acthar ®

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Signed informed consent and authorization of use and disclosure of protected health information
• Patients undergoing surgery for retinal detachment due to PVR

You may not qualify if:

• Patients with poorly controlled diabetes mellitus (defined as HbA1C ≥ 8.0% on any anti-diabetic medications or insulin. If the patient is using any anti-diabetic medication/insulin, he becomes eligible if the medication is used continuously for \>30 days)
• Patients with poorly controlled hypertension (defined as systolic blood pressure \>180 mm Hg and/or diastolic blood pressure \>100 mm Hg at rest with up to 3 anti-hypertensive medications. If a patient's initial measurement exceeds these values, a second reading may be taken 30 or more mins later. If the patient is using any anti-hypertensives, he becomes eligible if the medication is used continuously for \>30 days)
• Patients with congestive heart failure
• Patients with scleroderma
• Patients with osteoporosis
• Patients with active systemic fungal infection
• Patients with active ocular herpes simplex
• Patients with prior or active bleeding peptic ulcer
• Pregnant patients or patients who wish to become pregnant during the course of the study (females of child-bearing age will be counselled to use contraception for the duration of the study)

Sponsors & Collaborators

• Johns Hopkins University: lead
• Mallinckrodt: collaborator

Study Sites (1)

Wilmer Eye Institute, Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Vitreoretinopathy, Proliferative

Interventions

Adrenocorticotropic Hormone

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Melanocortins; Pro-Opiomelanocortin; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormones, Anterior; Pituitary Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins

Study Officials

• Peter A Campochiaro, MD

  Wilmer Eye Institute, Johns Hopkins School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2018
• First Posted: November 1, 2018
• Study Start: August 19, 2019
• Primary Completion: July 7, 2023
• Study Completion: July 7, 2023
• Last Updated: August 8, 2023

Record last verified: 2023-08

Locations

US (1)