Adalimumab for Mucopolysaccharidosis

Not currently recruiting at 1 trial location

Overseen By Eva Villa-Lopez

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Must not be taking: Immune suppressants

Disqualifiers: Lymphoma, Active infection, TB, others

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effects of adalimumab, a medication, on joint and skeletal problems in individuals with mucopolysaccharidosis (MPS) types I, II, or VI. The study compares adalimumab to a placebo to determine its effectiveness in reducing joint pain and improving movement. Individuals with MPS who experience significant pain and joint movement issues may be suitable for the trial. Participants will initially receive either the medication or placebo, followed by an opportunity to take adalimumab openly in a later phase. As a Phase 1 and Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to early-stage medical advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on immune suppression therapy, you must have stopped it at least 1 year before joining the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that adalimumab is generally safe and well-tolerated. In several studies, patients using adalimumab experienced better movement, improved physical function, and less pain. Even in small early studies, this treatment showed promising results without major safety issues.

The FDA has already approved adalimumab for other conditions, providing some confidence about its safety. However, each new trial gathers more specific information for different conditions, such as mucopolysaccharidosis (MPS).

While the treatment is still in the early stages of testing for MPS, previous findings suggest it is likely manageable for most patients. Always consult a healthcare provider about any concerns before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for mucopolysaccharidosis?

Unlike the standard treatments for mucopolysaccharidosis, which often include enzyme replacement therapies, Adalimumab stands out by targeting inflammation more directly. Most treatments focus on replacing missing enzymes, but Adalimumab, a monoclonal antibody, works by inhibiting tumor necrosis factor-alpha (TNF-alpha), a substance that can cause inflammation and damage in tissues. This approach could potentially help manage inflammation-related symptoms more effectively. Researchers are excited about Adalimumab because it offers a new mechanism to tackle the condition, which might lead to improved quality of life for patients.

What evidence suggests that adalimumab might be an effective treatment for mucopolysaccharidosis?

Research has shown that adalimumab might help people with mucopolysaccharidosis (MPS) types I, II, or VI. In this trial, participants may receive adalimumab, which studies suggest can improve mobility, assist with physical activities, and potentially reduce pain. Previous findings indicate it is safe and tolerable for users. Although more information is needed, the potential benefits for joint and bone problems appear promising. For those considering joining this trial, these early results might offer hope for managing MPS symptoms. ^{1 2 3 4 6}

Who Is on the Research Team?

Lynda Polgreen, MD, MS

Principal Investigator

The Lundquist Institute at Harbor-UCLA Medical Center

Are You a Good Fit for This Trial?

This trial is for children and adults over 5 years old with Hurler Syndrome, Hunter Syndrome, or Maroteaux-Lamy Syndrome who have either been treated with ERT for at least a year or not treated at all. Participants must have joint motion limitations in at least 3 joints, weigh more than 15 kg, and experience significant pain.

Inclusion Criteria

Patient or parent/legal guardian is able and willing to provide informed consent. For patients 7 to 17 years of age, assent must also be provided

I weigh at least 15 kilograms.

I experience more pain than most people do.

Exclusion Criteria

I had a stem cell transplant less than 2 years ago.

I will not be exposed to live vaccines during the study.

I have tested positive for TB or been recently exposed to it.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive adalimumab or placebo for 16 weeks to evaluate effects on joint and skeletal disease

16 weeks

Open-label

Participants receive open-label adalimumab treatment for 32 weeks

32 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Adalimumab

Trial Overview

The study tests the safety and effectiveness of Adalimumab injections compared to saline solution (placebo) on joint and skeletal disease in patients with MPS I, II or VI. It's randomized and double-blind: participants don't know if they're getting the real drug or placebo.

How Is the Trial Designed?

Group I: Open-label adalimumab Experimental Treatment 1 Intervention

Open-label extension of adalimumab dose

Group II: Adalimumab Experimental Treatment 1 Intervention

20 mg subQ every other week (weight 15to \<30 kg) 40 mg subQ every other week (weight ≥30 kg). Non-responders will be escalated to weekly dosing.

Group III: Placebo Placebo Group 1 Intervention

Saline placebo comparator

Adalimumab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Humira for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Crohn's disease
• Ulcerative colitis
• Plaque psoriasis
• Juvenile idiopathic arthritis

Approved in United States as Humira for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Crohn's disease
• Ulcerative colitis
• Plaque psoriasis
• Juvenile idiopathic arthritis
• Hidradenitis suppurativa

Approved in Canada as Humira for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Crohn's disease
• Ulcerative colitis
• Plaque psoriasis
• Juvenile idiopathic arthritis

Approved in Japan as Humira for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Crohn's disease
• Ulcerative colitis
• Plaque psoriasis
• Juvenile idiopathic arthritis

Who Is Running the Clinical Trial?

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Lead Sponsor

Trials

105

Recruited

46,600+

McGill University Health Centre/Research Institute of the McGill University Health Centre

Collaborator

Trials

476

Recruited

170,000+

Published Research Related to This Trial

Adalimumab is an effective treatment for rheumatoid arthritis and is expected to be approved for other conditions like psoriasis and ankylosing spondylitis, with a favorable side effect profile compared to traditional treatments, as it does not require regular lab monitoring.

However, it carries a two-fold increased risk of serious infections, particularly tuberculosis, and should not be used during active infections; careful screening and monitoring for side effects are essential for safe use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab: a review of side effects. Scheinfeld, N.[2022]

In a post hoc analysis of the GO-ALIVE study involving 112 ankylosing spondylitis patients, those with early disease showed significantly better responses to IV golimumab compared to those with late disease, indicating that earlier treatment may lead to more effective outcomes.

Patients with early disease experienced higher rates of improvement in disease activity measures at week 16, and while adverse events were reported, they were less frequent in early disease patients (46% vs. 61% in late disease), suggesting a favorable safety profile for early treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Intravenous Golimumab in Ankylosing Spondylitis Patients With Early and Late Disease Through One Year of the GO-ALIVE Study. Deodhar, AA., Shiff, NJ., Gong, C., et al.[2023]

Adalimumab has been shown to be generally safe and well tolerated in patients with rheumatoid arthritis, based on safety data from over 10,000 patients and 12,506 patient-years of exposure in clinical trials.

The rate of serious infections was consistent with previous reports, and after implementing tuberculosis screening, the incidence of TB cases decreased significantly, indicating effective monitoring and management of potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety analyses of adalimumab (HUMIRA) in global clinical trials and US postmarketing surveillance of patients with rheumatoid arthritis. Schiff, MH., Burmester, GR., Kent, JD., et al.[2022]

In a study involving 15,132 patients with rheumatoid arthritis, adalimumab was found to have a well-established safety profile, with serious infections occurring at a low rate of 4.7 events per 100 patient-years and no significant laboratory abnormalities compared to placebo.

The analysis also indicated that pregnancy outcomes for women exposed to adalimumab were similar to those of unexposed women with rheumatoid arthritis and healthy women, with no increased risk of major birth defects or spontaneous abortions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab long-term safety: infections, vaccination response and pregnancy outcomes in patients with rheumatoid arthritis. Burmester, GR., Landewé, R., Genovese, MC., et al.[2022]

In a study of 403 ankylosing spondylitis patients treated with adalimumab over 24 weeks, there was a significant reduction in disease activity, with a mean decrease of 2.0 in BASDAI scores, indicating effective treatment.

The safety profile was acceptable, with serious adverse drug reactions occurring in 3.79% of patients, which aligns with findings from previous clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world effectiveness and safety of adalimumab for treatment of ankylosing spondylitis in Japan. Kobayashi, S., Kashiwagi, T., Kimura, J.[2020]

Adalimumab, a monoclonal antibody that targets TNF-alpha, has been shown to significantly improve symptoms of rheumatoid arthritis in patients who did not respond adequately to other treatments, with higher response rates (ACR20, ACR50, ACR70) compared to placebo over 24-52 weeks.

The treatment not only provides rapid and sustained efficacy but also slows down joint damage and enhances quality of life, making it a valuable option for adults with active rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab: a review of its use in rheumatoid arthritis. Bang, LM., Keating, GM.[2018]

Adalimumab (ADA) is an effective treatment for rheumatoid arthritis (RA) and other inflammatory conditions, and can be used alone or with other medications like methotrexate.

This study compares the safety and effectiveness of ADA with other TNF-α inhibitors, etanercept and infliximab, highlighting the need for more direct comparisons in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab in the treatment of rheumatoid arthritis. Voulgari, PV., Kaltsonoudis, E., Papagoras, C., et al.[2022]

Adalimumab is generally safe for treating psoriasis, with most side effects being mild, such as injection site reactions and upper respiratory infections, which typically do not require stopping the medication.

Serious adverse effects, although rare, can include severe infections and autoimmune conditions, highlighting the need for careful patient screening and monitoring during treatment and for five months afterward.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Safety of adalimumab]. Ferran, M., Pujol, RM.[2015]

In a study involving 838 patients with polyarticular-course juvenile idiopathic arthritis, adalimumab (ADA) was found to be well tolerated, with no deaths or malignancies reported over a 7-year period.

Patients starting treatment with ADA ± methotrexate showed a trend towards lower disease activity compared to those on methotrexate alone, suggesting ADA may be more effective in managing symptoms in the first year.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Effectiveness of Adalimumab in Patients With Polyarticular Course of Juvenile Idiopathic Arthritis: STRIVE Registry Seven-Year Interim Results. Brunner, HI., Nanda, K., Toth, M., et al.[2020]

Citations

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5238608/

Pilot study of the safety and effect of adalimumab on pain ...

Data from this small pilot study suggest that treatment with adalimumab is safe, tolerable, and may improve ROM, physical function, and possibly pain, in ...

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clinicaltrials.gov

clinicaltrials.gov/study/NCT02437253

Effects of Adalimumab in Mucopolysaccharidosis Types I, II ...

The study physicians believe that the potential benefit of adalimumab on pain, quality of life, and other MPS related problems outweigh the potential risks of ...

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Data from this small pilot study suggest that treatment with adalimumab is safe, tolerable, and may improve ROM, physical function, and possibly ...

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ctsi.lundquist.org

ctsi.lundquist.org/case-studies/adalimumab-in-mps-i-ii-and-vi/

Adalimumab in MPS I, II, and VI - CTSI

This study is a randomized, double-blind, placebo-controlled, parallel-group, single-center study followed by open-label phase, to evaluate the effects of ...

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This study is a randomized, double-blind, placebo-controlled, parallel-group, single-center study followed by open-label phase, to evaluate the effects of ...

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researchgate.net

researchgate.net/publication/312382698_Pilot_study_of_the_safety_and_effect_of_adalimumab_on_pain_physical_function_and_musculoskeletal_disease_in_mucopolysaccharidosis_types_I_and_II

Pilot study of the safety and effect of adalimumab on pain ...

[Show full abstract] objective of this study was to evaluate the effects of laronidase on somatic outcomes of patients with MPS IH previously treated with HCT.