Evaluating the Use of Prednisone to Decrease Pegylated Interferon Beta-1a Side Effects

• ClinicalTrials.gov Identifier: NCT03424733
• Recruitment Status: Recruiting
• First Posted: February 7, 2018
• Last Update Posted: August 15, 2019
• Sponsor: Holy Name Medical Center, Inc.
• Collaborator: Biogen
• Information provided by (Responsible Party): Mary Ann Picone, MD, Holy Name Medical Center, Inc.

Study Description

Brief Summary:

Some of the most common side effects of the multiple sclerosis drug Plegridy (pegylated interferon beta-1a) include flu-like symptoms and injection site reactions. Physicians often advise patients to take Tylenol or aspirin prior to injection, but in this study the investigators evaluated whether using a low dose of oral steroid in combination with Tylenol reduced flu-like symptoms and injection site reactions.

Condition or disease	Intervention/treatment	Phase
Multiple Sclerosis	Drug: Plegridy; Drug: Prednisone; Drug: Tylenol Pill	Phase 4

Detailed Description:

Multiple Sclerosis (MS) is a chronic neurological disease characterized by demyelination of the brain and spine. Currently, there are several treatments designed to decrease the frequency of attacks and delay disease progression. One of these treatments, interferon beta, has shown the potential to decrease relapse rates by approximately 30%, but because the body quickly clears these proteins, patients require more frequent dosing. Another interferon therapy called pegylated interferon beta-1a (Plegridy) was released and it was shown to last longer in the body than interferon beta-1a. This is why Plegridy can be take by an injection into tissue under the skin once every 14 days. However, some of the most common side effects of interferon beta therapy include flu-like symptoms and injection skin reactions, which can often cause patients to want to stop treatment. Clinical practitioners often advise patients to take acetaminophen (Tylenol) or aspirin before the injection in order to prevent the onset or decrease the severity of flu-like symptoms. A previous study with patients taking interferon beta-1a showed that taking a low dose oral steroid (prednisone) in addiction to a medication like Tylenol reduced flu-like symptoms compared to just taking Tylenol by itself. Because Plegridy lasts longer in the body and has more convenient dosing for patients, researchers in this study decided to investigate whether taking prednisone in addition to acetaminophen before the injection would help decrease or prevent the occurrence of flu-like symptoms and injection site reactions in patients taking the therapy.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 50 participants
• Allocation: Non-Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Patients in both arms first take Tylenol and then take Tylenol in combination with Prednisone.
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Trial of Prednisone and Acetaminophen Versus Acetaminophen Alone in Minimizing Flu-like Symptoms From Pegylated Interferon Beta-1a
• Actual Study Start Date: September 25, 2017
• Estimated Primary Completion Date: May 1, 2020
• Estimated Study Completion Date: May 31, 2020

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Current Plegridy Users; Members in this group have been previously titrated and are currently taking the pegylated interferon beta-1 (Plegridy) injection once every two weeks. These patients will complete a total of six study injections of Plegridy (125 micrograms) totaling a 12 week study duration. Subjects must take two 325mg tablets of Tylenol 1 hour prior to each study injection, and one 20mg Prednisone tablet 4-5 hours prior to injections two through six only.	Drug: Plegridy; Self injection into area of high adipose content. Injections include 63 and 94 microgram titration doses, and the full 125 microgram dose; Other Name: Pegylated Interferon beta-1a; Drug: Prednisone; Take one 20 milligram prednisone tablet four to five hours prior to injections two through six of the full 125 microgram Plegridy dose.; Drug: Tylenol Pill; Take two 325 milligram Tylenol tablets 1 hour prior to each Plegridy injection, irregardless of dosage.; Other Name: Acetaminophen
Experimental: New Plegridy Users; Members in this group have never taken the pegylated interferon beta-1a (Plegridy) injection, and so they must first by titrated by injecting with a 63 and 94 microgram Plegridy dose. Titrations, along with full dose injections (125 micrograms) occur every two weeks. Patients must take two 325mg tablets of Tylenol prior to each titration injection. The third study dosage involves subjects taking the full 125 microgram Plegridy dosage with two 325mg Tylenol tablets prior to injection. The final five study injections (four through eight) require patients to take two 325mg Tylenol tablets 1 hour prior to injection, and one 20mg Prednisone tablet 4-5 hours prior to injection.	Drug: Plegridy; Self injection into area of high adipose content. Injections include 63 and 94 microgram titration doses, and the full 125 microgram dose; Other Name: Pegylated Interferon beta-1a; Drug: Prednisone; Take one 20 milligram prednisone tablet four to five hours prior to injections two through six of the full 125 microgram Plegridy dose.; Drug: Tylenol Pill; Take two 325 milligram Tylenol tablets 1 hour prior to each Plegridy injection, irregardless of dosage.; Other Name: Acetaminophen

Outcome Measures

Primary Outcome Measures :

1. Flu-like symptoms [ Time Frame: 12 to 16 weeks ]
   Reduced flu-like symptoms from Plegridy injections due to taking both Tylenol and Prednisone prior to treatment. Flu-like symptoms are measured every 6 hours for 48 hours after injection by patients self reporting their muscle aches, temperature, chills, and fatigue on a Holy Name administered Flu-like symptom questionnaire.

Secondary Outcome Measures :

1. Injection site reactions [ Time Frame: 12 to 16 weeks ]
   Reduced injection site reactions from Plegridy injections due to taking both Tylenol and Prednisone prior to injection. Injection site reactions are reported to a clinical research assistant approximately one week after injection. If present, patients must record their injection site reactions using a Holy Name administered tape measurer in centimeters, as well as descriptive characteristics of the injection (location on body, swelling, redness, itching, and pain). The clinical research assistant records all of the data on an injection site reaction form.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• diagnosed any form of MS (relapsing remitting, primary progressive, secondary progressive), any EDSS (expanded stability status scale) score

Exclusion Criteria:

• prior allergic reaction to interferon products, congestive heart failure, elevated liver enzymes

Contacts and Locations

Contacts

Contact: Mary Ann Picone, MD; 201-837-0727; m-picone@mail.holyname.org

Locations

United States, New Jersey

Holy Name Medical Center; Recruiting

Teaneck, New Jersey, United States, 07666

Contact: Mary Ann Picone, MD 201-837-0727 M-picone@mail.holyname.org

Sponsors and Collaborators

Holy Name Medical Center, Inc.

Biogen

More Information

Publications of Results:

Río J, Nos C, Marzo ME, Tintoré M, Montalban X. Low-dose steroids reduce flu-like symptoms at the initiation of IFNbeta-1b in relapsing-remitting MS. Neurology. 1998 Jun;50(6):1910-2.

Brandes DW, Bigley K, Hornstein W, Cohen H, Au W, Shubin R. Alleviating flu-like symptoms with dose titration and analgesics in MS patients on intramuscular interferon beta-1a therapy: a pilot study. Curr Med Res Opin. 2007 Jul;23(7):1667-72.

Río J, Nos C, Bonaventura I, Arroyo R, Genis D, Sureda B, Ara JR, Brieva L, Martín J, Saiz A, Sánchez López F, Prieto JM, Roquer J, Dorado JF, Montalban X. Corticosteroids, ibuprofen, and acetaminophen for IFNbeta-1a flu symptoms in MS: a randomized trial. Neurology. 2004 Aug 10;63(3):525-8.

• Responsible Party: Mary Ann Picone, MD, Neurologist, Holy Name Medical Center, Inc.
• ClinicalTrials.gov Identifier: NCT03424733
• Other Study ID Numbers: US-PEG-16-10990
• First Posted: February 7, 2018
• Last Update Posted: August 15, 2019
• Last Verified: August 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Mary Ann Picone, MD, Holy Name Medical Center, Inc.:

demyelination; relapse rate; Pegylated interferon beta-1a; side effects; flu-like symptoms; injection site reactions; prednisone

Additional relevant MeSH terms:

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Acetaminophen; Interferons; Interferon-beta; Interferon beta-1a; Prednisone; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Antipyretics; Immunologic Factors; Adjuvants, Immunologic