Diffuse Cutaneous Systemic SclerosisPhase 1NCT04478994
A Study With TEPEZZA in Patients With Diffuse Cutaneous Systemic Sclerosis (dcSSc)
A Phase 1 study testing TEPEZZA in people with Diffuse Cutaneous Systemic Sclerosis, run by Amgen at 7 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Diffuse Cutaneous Systemic Sclerosis
- What is being tested?
- TEPEZZA
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 3 participants
- Where
- 7 sitesUnited States
- Study dates
- 17 Nov 2021to 8 Dec 2022
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- Use of a non-steroidal immunosuppressive agent, cytotoxic or anti-fibrotic drug within 4 weeks of Screening, including cyclophosphamide, azathioprine (Imuran®), methotrexate or other immunosuppressive or cytotoxic medication. Exceptions are mycophenolate mofetil (CellCept) and mycophenolic acid (Myfortic), which are permitted according to inclusion criterion 8, and anti-malarials (e.g., hydroxychloroquine [Plaquenil®]).
- 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.
- Previous organ transplant (including allogeneic and autologous marrow transplant).
- Alanine aminotransferase or aspartate aminotransferase >2.5 times the upper limit of normal or estimated glomerular filtration rate of <30 mL/min/1.73m^2 at Screening.
- Platelets <100×10^3/µL.
- Hemoglobin <8 g/dL.
- Any other condition that, in the opinion of the Investigator, would preclude inclusion in the study.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
The Johns Hopkins Bayview Medical Center
Baltimore, Maryland, 21224
The Cleveland Clinic
Cleveland, Ohio, 44195
UT Physicians Center for AutoImmunity
Houston, Texas, 77030
UCLA Division of Rheumatology
Los Angeles, California, 900095-1670
Pacific Arthritis Care Center
Los Angeles, California, 90045
Yale North Haven Medical Center
New Haven, Connecticut, 06473
University of Toledo Medical Center
Toledo, Ohio, 43614
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled, Repeat-Dose, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics, and Explore Efficacy of TEPEZZA in Patients With Diffuse Cutaneous Systemic Sclerosis
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).
Read the detailed description
This is a randomized, double-blind, placebo-controlled, repeat-dose, multicenter study. Participants will be screened for the study within 4 weeks prior to the Baseline (Day 1) Visit. Approximately 25 participants who meet the study eligibility criteria will be randomized on Day 1 in a 3:2 ratio to receive 8 infusions of TEPEZZA or placebo q3W. During the 24-week double-blind Treatment Period, study drug will be infused on Day 1 (Baseline) and Weeks 3, 6, 9, 12, 15, 18 and 21 with a comprehensive visit at Week 24 (end of treatment). On each dosing day, scheduled assessments (except for Adverse Events [AE] and concomitant medication use monitoring, which will be monitored throughout the clinic visit) will be completed prior to study drug infusions.
At the end of the Treatment Period (Week 24), participants will enter a 24-week Follow-up Period, during which study drug will not be administered and a clinic visit will be scheduled for Weeks 28, 36 and 48. A phone call or email at Weeks 32 and 42 will occur to inquire how the participant is doing.
Study acquired from Horizon in 2024.
- Conditions
- Diffuse Cutaneous Systemic Sclerosis
- Being tested
- TEPEZZA, Placebo
- Medical subject headings
- Scleroderma, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TEPEZZABiological
Also called teprotumumab-trbw, HZN-001
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).
PlaceboOther
Also called Saline solution
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).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: TEPEZZA |
| Placebo | Placebo comparator | Approximately 10 participants will receive 8 infusions of placebo q3W for a total of 21 weeks. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From first dose of trial drug up to Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2020
- Study start17 Nov 2021
- Primary completion29 Nov 2022
- Study completion8 Dec 2022
Why it stopped: Poor enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Diffuse Cutaneous Systemic SclerosisStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04478994
- Sponsor's protocol ID
- HZNP-TEP-001
- Status last verified
- Jun 2024
- First submitted
- 16 Jul 2020
- Last updated
- 28 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled, Repeat-Dose, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics, and Explore Efficacy of TEPEZZA in Patients With Diffuse Cutaneous Systemic Sclerosis
- ClinicalTrials.gov ID
- NCT04478994
- Acronym / sponsor ID
- HZNP-TEP-001
- Conditions
- Diffuse Cutaneous Systemic Sclerosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor enrollment
- Enrolment
- 3 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 17 Nov 2021 (actual)
- Primary completion
- 29 Nov 2022 (actual)
- Study completion
- 8 Dec 2022 (actual)
- First posted
- 21 Jul 2020 (actual)
- Results
- Posted 19 Apr 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
This is a randomized, double-blind, placebo-controlled, repeat-dose, multicenter study. Participants will be screened for the study within 4 weeks prior to the Baseline (Day 1) Visit. Approximately 25 participants who meet the study eligibility criteria will be randomized on Day 1 in a 3:2 ratio to receive 8 infusions of TEPEZZA or placebo q3W. During the 24-week double-blind Treatment Period, study drug will be infused on Day 1 (Baseline) and Weeks 3, 6, 9, 12, 15, 18 and 21 with a comprehensive visit at Week 24 (end of treatment). On each dosing day, scheduled assessments (except for Adverse Events [AE] and concomitant medication use monitoring, which will be monitored throughout the clinic visit) will be completed prior to study drug infusions.
At the end of the Treatment Period (Week 24), participants will enter a 24-week Follow-up Period, during which study drug will not be administered and a clinic visit will be scheduled for Weeks 28, 36 and 48. A phone call or email at Weeks 32 and 42 will occur to inquire how the participant is doing.
Study acquired from Horizon in 2024.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TEPEZZA 20mg/kg | Active comparator | Biological: TEPEZZAApproximately 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. |
| Placebo | Placebo comparator | Other: PlaceboApproximately 10 participants will receive 8 infusions of placebo q3W for a total of 21 weeks. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (21 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TEPEZZAAlso: teprotumumab-trbw, HZN-001TEPEZZA 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). | Biological | TEPEZZA 20mg/kg |
| PlaceboAlso: Saline solutionPlacebo 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). | Other | Placebo |
Primary outcome
Number of Participants Experiencing a Treatment Emergent Adverse Event (TEAE) Through Week 24
Time frame: From first dose of trial drug up to 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TEPEZZA in people with Diffuse Cutaneous Systemic Sclerosis, run by Amgen at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Experiencing a Treatment Emergent Adverse Event (TEAE) Through Week 24 (time frame: From first dose of trial drug up to Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2024.