Denosumab for Osteoporosis in Cystic Fibrosis

Overseen By Ashley Keller

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Texas Southwestern Medical Center

Disqualifiers: No CF diagnosis, No osteoporosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 11

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how well Denosumab (also known as Prolia or Xgeva) works for individuals with cystic fibrosis (CF) who have bone diseases like osteoporosis. In the main study, both CF patients and healthy volunteers will attend a single visit to assess bone health through scans and blood tests. CF patients with bone disease may join a sub-study to receive Denosumab injections every six months for up to five years. Eligible participants must have a confirmed CF diagnosis and be willing to attend annual check-ups. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective Denosumab can benefit more patients with CF-related bone disease.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the study coordinators for more details.

What is the safety track record for Denosumab?

Research shows that denosumab, a treatment for bone disease, presents some safety concerns. Studies have found a risk of heart problems, such as heart attacks and strokes, and a higher chance of serious infections, including those affecting the skin, abdomen, and urinary tract.

Despite these risks, long-term studies on denosumab have demonstrated some positive outcomes. After up to 10 years of use, some patients maintained normal bone health and improved bone density. This suggests that denosumab may benefit bone health over time.

Since this trial is in a later stage, more safety information is available compared to earlier stages. Denosumab has been studied more thoroughly for safety, though risks still need consideration. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Denosumab is unique because it offers a targeted approach to treating osteoporosis in cystic fibrosis patients by inhibiting a protein called RANKL, which plays a crucial role in bone resorption. Unlike traditional treatments like bisphosphonates, which also aim to prevent bone loss but through different pathways, denosumab's mechanism can effectively reduce bone turnover, potentially leading to stronger bones. Researchers are excited because this treatment is administered via a convenient subcutaneous injection every six months, which could improve patient adherence compared to other therapies requiring more frequent dosing.

What evidence suggests that Denosumab might be an effective treatment for osteoporosis in cystic fibrosis?

Research shows that denosumab effectively treats osteoporosis, a bone disease, in people with cystic fibrosis (CF). Although specific data for CF is limited, denosumab has increased bone strength and reduced fracture risk in other osteoporosis patients. In this trial, participants in the Denosumab Sub-study will receive denosumab, which targets a protein called RANKL. This protein is often elevated in CF-related bone disease, and denosumab helps strengthen bones. Experts agree that it improves bone health in osteoporosis generally, offering hope for those with CF-related bone issues. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with Cystic Fibrosis (CF) who have been diagnosed with osteoporosis. Participants must be able to understand and write in English, and willing to return for annual study visits over a period of up to five years.

Inclusion Criteria

Subjects (and parents/legal guardians as applicable) must have the ability to read and write in English

My cystic fibrosis diagnosis was confirmed by a sweat test or genetic test.

Exclusion Criteria

I do not have cystic fibrosis.

I am not willing to commit to yearly study visits for 5 years.

I am under 18 years old.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Main Study

Participants undergo a single study visit including a DEXA scan, micro CT, and blood collection

1 day

1 visit (in-person)

Denosumab Sub-study

Participants with bone disease receive Denosumab treatment every 6 months and annual assessments

5 years

10 visits (in-person) over 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Denosumab

Trial Overview The trial is testing Denosumab's effectiveness on bone disease in CF patients. It involves an initial study visit with scans and blood tests, followed by selected patients receiving Denosumab treatment annually for up to five years.

How Is the Trial Designed?

Group I: Denosomab Sub-study Experimental Treatment 1 Intervention

Approximately 10 subjects with CF that have completed the main study and have results which indicate bone disease are eligible to participate in the sub study. Subjects who consent will receive treatment with denosumab (60 mg/ml via subcutaneous injection in the upper arm, upper thigh, or abdomen every 6 months) for up to 5 years. These subjects will be asked to return every 6 months for injections and annually (+/- 6 months) for up to 5 years for a DEXA scan, micro CT, and blood collection.

Group II: Main Study Active Control 1 Intervention

Up to 100 subjects, both non-CF volunteers and Cystic Fibrosis (CF) patients, will participate in a single study visit that will include a DEXA scan (if not completed as standard of care within 6 months prior to research visit), micro CT, and blood collection.

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

Approved in European Union as Prolia for:

• Osteoporosis in postmenopausal women
• Bone loss associated with hormone ablation therapy for prostate cancer
• Bone loss associated with hormone ablation therapy for breast cancer

Approved in United States as Prolia for:

• Treatment of postmenopausal women with osteoporosis at high risk for fracture
• Treatment to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer
• Treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer

Approved in Canada as Prolia for:

• Treatment of osteoporosis in postmenopausal women at high risk for fracture
• Treatment to increase bone mass in men with osteoporosis at high risk for fracture

Approved in Japan as Prolia for:

• Treatment of osteoporosis in postmenopausal women
• Treatment of bone loss associated with hormone ablation therapy for prostate cancer

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Published Research Related to This Trial

Cystic fibrosis patients experience significant bone health issues, including premature osteopenia and osteoporosis, due to factors like delayed puberty, malabsorption, and corticosteroid use, leading to a higher risk of fractures and kyphosis.

Regular monitoring of bone mineral density using dual energy X-ray absorptiometry is recommended for all cystic fibrosis patients starting in adolescence, and early treatment with bisphosphonates shows promise in improving bone health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of lung inflammation on bone metabolism in adolescents with cystic fibrosis. Conway, SP.[2009]

In a study of 16 pre-pubertal children with cystic fibrosis (CF) and 16 control children, bone mineral density (BMD) was found to be normal and comparable between both groups, suggesting that younger, well-nourished CF patients may not experience significant bone density issues at this age.

Despite normal BMD, CF patients exhibited lower serum osteocalcin and higher alkaline phosphatase and vitamin D levels, indicating potential early metabolic changes that could lead to bone disease as they age, highlighting the need for future studies to explore these relationships further.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relation of bone mineral density with clinical and laboratory parameters in pre-pubertal children with cystic fibrosis. Cobanoglu, N., Atasoy, H., Ozcelik, U., et al.[2013]

Patients with cystic fibrosis are at a higher risk for low bone mineral density and fragility fractures, highlighting the need for careful monitoring of bone health in these individuals.

The paper provides consensus statements based on current knowledge and expert validation, offering guidance on assessing, preventing, and treating skeletal deficits associated with cystic fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European cystic fibrosis bone mineralisation guidelines. Sermet-Gaudelus, I., Bianchi, ML., Garabédian, M., et al.[2022]

A case study of a 46-year-old woman with cystic fibrosis-related bone disease showed that treatment with romosozumab led to significant improvements in bone mineral density after one year, indicating its potential efficacy.

This report suggests that romosozumab could be a promising alternative treatment for patients with cystic fibrosis at high risk for fractures, but further research is needed to confirm its safety and effectiveness in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Romosozumab used to treat a patient with cystic fibrosis-related osteoporosis. Crow, HM., Graves, L., Anabtawi, A.[2023]

In a study involving 171 young patients with cystic fibrosis, treatment with calcium and calcifediol improved bone mineral density in 25% of participants, indicating that proper calcium intake can be beneficial for bone health in these patients.

For those who did not respond to the initial treatment, alendronate significantly increased bone mineral density by 16.3% compared to just 3.1% in the placebo group, demonstrating its efficacy and safety in improving bone health in young individuals with cystic fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of low bone density in young people with cystic fibrosis: a multicentre, prospective, open-label observational study of calcium and calcifediol followed by a randomised placebo-controlled trial of alendronate. Bianchi, ML., Colombo, C., Assael, BM., et al.[2022]

In a study of 17 young adult cystic fibrosis patients, normal bone mineral density (BMD) was observed despite abnormal bone turnover, with increased levels of bone formation markers (osteocalcin and PICP) and normal levels of bone resorption marker (ICTP).

BMD was positively correlated with pulmonary function, suggesting that better lung health may support bone health in cystic fibrosis patients, while inflammatory markers like IL-6 were inversely correlated with bone formation markers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of bone mineral density and turnover in patients with cystic fibrosis: associations between the IGF system and inflammatory cytokines. Street, ME., Spaggiari, C., Ziveri, MA., et al.[2015]

In a year-long study involving 48 adults with cystic fibrosis, alendronate significantly improved bone mineral density at the spine and femur compared to placebo, with increases of 4.9% and 2.8% respectively, while the placebo group experienced losses in bone density.

The treatment also reduced levels of urine N-telopeptide, a marker of bone resorption, indicating that alendronate effectively inhibits bone loss, making it a promising option for managing bone health in cystic fibrosis patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of alendronate in adults with cystic fibrosis with low bone density. Aris, RM., Lester, GE., Caminiti, M., et al.[2013]

Adults with late-stage cystic fibrosis have severely decreased bone mineral density, averaging 2 standard deviations below normal, leading to significantly higher fracture rates, particularly in younger women and middle-aged men.

Osteoporosis in these patients is associated with severe kyphosis and height loss, with cumulative prednisone use, body mass index, and age at puberty identified as key predictors of bone mineral density.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased rate of fractures and severe kyphosis: sequelae of living into adulthood with cystic fibrosis. Aris, RM., Renner, JB., Winders, AD., et al.[2019]

In a study of 56 adults with cystic fibrosis and low bone mass, alendronate therapy significantly increased lumbar spine bone mineral density (BMD) by 5.20% compared to a slight decrease in the placebo group, indicating its efficacy in improving bone health.

The treatment was well tolerated with no significant differences in quality of life or adverse events between the alendronate and placebo groups, suggesting it is a safe option for patients with cystic fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alendronate once weekly for the prevention and treatment of bone loss in Canadian adult cystic fibrosis patients (CFOS trial). Papaioannou, A., Kennedy, CC., Freitag, A., et al.[2021]

In a study of 64 adults with cystic fibrosis, 52% were found to have low bone mineral density (BMD), with male sex, short stature, and low lean mass being significant predictors of this condition.

Over a 2-year period, lower lung function and higher fat mass index were linked to greater loss of BMD, highlighting the importance of maintaining lung health and lean body mass in managing bone health in cystic fibrosis patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Body composition, lung function, and prevalent and progressive bone deficits among adults with cystic fibrosis. Baker, JF., Putman, MS., Herlyn, K., et al.[2020]

In a study of 57 patients with cystic fibrosis aged 3 to 21 years, it was found that they had significantly lower vertebral bone density (10% lower) compared to a matched control group, indicating a high prevalence of osteoporosis in this population.

The study revealed that lower bone density was associated with poorer nutritional status and greater disease severity, suggesting that managing nutrition and disease progression may be important for improving bone health in cystic fibrosis patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osteoporosis in cystic fibrosis. Gibbens, DT., Gilsanz, V., Boechat, MI., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8760456/

Treatment of cystic fibrosis related bone disease - PMC There is theoretical evidence that denosumab might be beneficial in CFBD [73] because murine models show that CFTR knockout mice osteoblasts have a higher RANKL ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1569199319308690

Cystic fibrosis bone disease treatment: Current knowledge ... Most of the available data are based on clinical trials of bisphosphonates in postmenopausal women showing fracture reduction efficacy after 3–5 years and as ...

3. clinicaltrial.be clinicaltrial.be/en/details/64112?per_page=100&only_recruiting=1&only_eligible=0&only_active=0

Markers of Osteoporosis in Cystic Fibrosis - Clinical Tri... Denosumab (Prolia) Sub study Approximately 10 adult subjects with CF who participated in the main study and have results indicating bone disease ...

4. withpower.com withpower.com/trial/phase-4-osteoporosis-9-2021-69099

Denosumab for Osteoporosis in Cystic Fibrosis In a year-long study involving 48 adults with cystic fibrosis, alendronate significantly improved bone mineral density at the spine and femur compared to ...

5. journals.sagepub.com journals.sagepub.com/doi/10.1177/20420188251328210

Cystic fibrosis-related bone disease: an update on ... A 2023 Cochrane Review, Bisphosphonates for osteoporosis in people with CF, found no significant difference between fractures in the treatment ...

6. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/441800

Markers of Osteoporosis in Cystic Fibrosis Denosumab (Prolia) Sub study Approximately 10 adult subjects with CF who participated in the main study and have results indicating bone disease ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6037073/

Effects of Long-Term Denosumab on Bone Histomorphometry ... After up to 10 years of denosumab therapy, iliac bone biopsies from postmenopausal women showed normal histology, reduced bone remodeling, and increased matrix ...