A Study With TEPEZZA in Patients With Diffuse Cutaneous Systemic Sclerosis (dcSSc)

NCT04478994 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: HZNP-TEP-001
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 7

Brief Summary

The overall objective is to investigate the safety, tolerability and effect on insulin-like growth factor-1 (IGF-1), inflammatory and fibrotic biomarkers of TEPEZZA (teprotumumab-trbw, HZN-001), a fully human monoclonal antibody (mAb) inhibitor of the IGF-1 receptor (IGF-1R), administered once every 3 weeks (q3W) for 24 weeks in the treatment of participants with diffuse cutaneous systemic sclerosis (dcSSc).

Conditions

Diffuse Cutaneous Systemic Sclerosis

Outcome Measures

Primary Outcomes (1)

• Number of Participants Experiencing a Treatment Emergent Adverse Event (TEAE) Through Week 24

  An adverse event (AE) is any untoward medical occurrence, which does not necessarily have a causal relationship with treatment. TEAEs are those that occurred after the first dose of trial drug.

  From first dose of trial drug up to Week 24

Study Arms (2)

TEPEZZA 20mg/kg

ACTIVE COMPARATOR

Approximately 15 participants will receive 8 infusions of TEPEZZA q3W for a total of 21 weeks. TEPEZZA 10mg/kg will be administered on Day 1 and TEPEZZA 20mg/kg will be administered q3W for the remaining 7 infusions.

Biological: TEPEZZA

Placebo

PLACEBO COMPARATOR

Approximately 10 participants will receive 8 infusions of placebo q3W for a total of 21 weeks.

Other: Placebo

Interventions

TEPEZZA BIOLOGICAL

TEPEZZA is a fully human anti-IGF-1R mAb. TEPEZZA will be provided in single-dose 20 mL glass vials as a freeze-dried powder. Each vial of TEPEZZA must be reconstituted with 10 mL of water for injection. Reconstituted TEPEZZA solution must be further diluted in 0.9% (w/v) sodium chloride (NaCl) solution prior to administration. TEPEZZA will be administered in 100 mL or 250 mL infusion bags (100 mL infusion bags for doses up to 1800 mg and 250 mL infusion bags for doses \> 1800 mg).

Also known as: teprotumumab-trbw, HZN-001

TEPEZZA 20mg/kg

Placebo OTHER

Placebo will consist of normal saline (0.9% NaCl) solution and will be administered in 100 mL or 250 mL infusion bags, as would be appropriate, per weight-based dosing volumes (100 mL infusion bags for doses up to 1800 mg and 250 mL infusion bags for doses \> 1800 mg).

Also known as: Saline solution

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent.
• Male or female between the ages of 18 and 80 years, inclusive, at Screening.
• Meets the 2013 American College of Rheumatology/European League Against Rheumatism classification criteria for systemic sclerosis (SSc) with a total score of ≥9.
• Classified as having skin involvement proximal to elbow, knee, face and neck.
• At the time of enrollment, no more than 60 months must have elapsed since the onset of the first dcSSc manifestations, other than Raynaud's phenomenon.
• Skin thickening from dcSSc in the forearm suitable for repeat biopsy.
• Modified Rodman Skin Score (mRSS) units ≥10 and ≤45 at Screening.
• Participant will be allowed to take CellCept® (mycophenolate mofetil) up to 3 g/day or Myfortic® (mycophenolic acid) up to 2.14 g/day and low-dose prednisone (≤10 mg/day or equivalent dosing of glucocorticoids). Participants taking CellCept or Myfortic have been doing so for ≥20 weeks and the dose must have been stable for ≥16 weeks prior to the Day 1 Visit. Prednisone must have been at a stable dose for ≥4 weeks prior to the Day 1 Visit.
• Diabetic participants must have glycated hemoglobin (HbA1c) ≤8.0%, with no new diabetic medication (oral or insulin) or more than a 10% change in the dose of a currently prescribed diabetic medication within 60 days prior to Screening.
• Women of childbearing potential (including those with an onset of menopause \<2 years prior to Screening, nontherapy-induced amenorrhea for \<12 months prior to Screening or not surgically sterile \[absence of ovaries and/or uterus\]) must have a negative serum pregnancy test at Screening and negative urine pregnancy tests at all protocol-specified timepoints (i.e., prior to each dose and throughout the participant's participation in the Follow-up Period); participants who are sexually active with a non vasectomized male partner must agree to use 2 reliable forms of contraception during the trial, one of which is recommended to be hormonal, such as an oral contraceptive. Hormonal contraception must be started at least one full cycle prior to Baseline and continue for 180 days after the last dose of study drug. Highly effective contraceptive methods (with a failure rate \<1% per year), when used consistently and correctly, include implants, injectables, combined oral contraceptives, some intrauterine devices, sexual abstinence or vasectomized partner.
• Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the study.

You may not qualify if:

• Diagnosed with limited cutaneous SSc or sine scleroderma.
• Diagnosed with other autoimmune connective tissue diseases, except for fibromyalgia, scleroderma associated myopathy and Sjogren's syndrome.
• Scleroderma renal crisis diagnosed within 6 months of the Screening Visit, characterized by abrupt onset of hypertension and acute kidney injury.
• Forced vital capacity (FVC) \<50% predicted, diffusing capacity of the lungs for carbon monoxide (DLCO) \<40% predicted or pulmonary arterial hypertension (PAH) by right heart catheterization requiring treatment with more than one oral PAH approved therapy or parenteral therapy (intermittent use of phosphodiesterase-5 inhibitors are allowed for erectile dysfunction and/or Raynaud's phenomenon/digital ulcers).
• Corticosteroid use for conditions other than dcSSc within 4 weeks prior to Screening (topical steroids for dermatological conditions and inhaled steroids are allowed).
• Previous treatment with rituximab (Rituxan® or MabThera®) within 12 months prior to the first infusion.
• Use of biologics or small molecules approved for rheumatoid arthritis, psoriatic arthritis and other rheumatic diseases within 4 weeks prior to Screening.
• Use of an investigational agent for any condition within 90 days or 5 half-lives, whichever is longer, prior to Screening or anticipated use during the course of the trial.
• Malignant condition in the past 5 years (except successfully treated basal/squamous cell carcinoma of the skin or cervical cancer in situ).
• Pregnant or lactating women.
• Current drug or alcohol abuse or history of either within the previous 2 years, in the opinion of the Investigator or as reported by the participant.
• Biopsy-proven or clinically suspected inflammatory bowel disease (e.g., diarrhea with or without blood or rectal bleeding associated with abdominal pain or cramping/colic, urgency, tenesmus or incontinence for more than 4 weeks without a confirmed alternative diagnosis OR endoscopic or radiologic evidence of enteritis/colitis without a confirmed alternative diagnosis).
• Known hypersensitivity to any of the components of TEPEZZA or prior hypersensitivity reactions to mAbs.
• Previous enrollment in this study or participation in a prior teprotumumab-trbw clinical trial.
• Human immunodeficiency virus, untreated or positive viral load for hepatitis C or hepatitis B infections.

Sponsors & Collaborators

• Amgen: lead

Study Sites (7)

UCLA Division of Rheumatology

Los Angeles, California, 900095-1670, United States

Location

Pacific Arthritis Care Center

Los Angeles, California, 90045, United States

Location

Yale North Haven Medical Center

New Haven, Connecticut, 06473, United States

Location

The Johns Hopkins Bayview Medical Center

Baltimore, Maryland, 21224, United States

Location

The Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Toledo Medical Center

Toledo, Ohio, 43614, United States

Location

UT Physicians Center for AutoImmunity

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Scleroderma, Diffuse

Interventions

teprotumumab; Saline Solution

Condition Hierarchy (Ancestors)

Scleroderma, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Medical Monitor
• Organization: Horizon Pharma USA, Inc.

medicalinformation@horizontherapeutics.com

1-866-479-6742

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2020
• First Posted: July 21, 2020
• Study Start: November 17, 2021
• Primary Completion: November 29, 2022
• Study Completion: December 8, 2022
• Last Updated: June 28, 2024
• Results First Posted: April 19, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

Locations

US (7)