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Burosumab for Fibroblast Growth Factor-23 Mediated Hypophosphatemia in Fibrous Dysplasia

Primary Purpose

Fibrous Dysplasia Of Bone

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Burosumab

About this trial

This is an interventional treatment trial for Fibrous Dysplasia Of Bone focused on measuring McCune-Albright Syndrome, Rickets, Osteomalacia, Metabolic Bone Disorders

Eligibility Criteria

1 Year - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

Confirmed diagnosis of fibrous dysplasia
Serum phosphate <10th percentile for age and sex, AND intact serum FGF23 >=30 pg/mL
Age >=1 year
Provision of signed and dated informed consent/assent form
Stated willingness of subject or Legally Authorized Representative (LAR) to comply with all study procedures and availability for the duration of the study
For females of reproductive potential: agreement to use highly effective contraception for during study participation. Highly effective contraception methods include:
- Total abstinence (when this is in line with the preferred and usual lifestyle of the participant). Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception
- Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment.
- Male sterilization (at least 6 months prior to screening). For female participants on the study the vasectomized male partner should be the sole partner for that participant.
- Combination of the following (a+b or a+c, or b+c):
  - Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception
  - Placement of an intrauterine device (IUD) or intrauterine system (IUS)
  - Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository
For males of reproductive potential: use of condoms or other methods described above to ensure effective contraception with partner
Minimum body weight of 7.5 kilograms

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

Pregnancy or lactation
Known allergic reactions to burosumab or drug component
Treatment with another investigational drug within 30 days of screening
Treatment with burosumab within 30 days of screening
Have any condition which in the opinion of the PI could present a concern for subject safety or difficulty with data interpretation
Severe renal impairment or end stage renal disease, defined as: pediatric patients with estimated glomerular filtration rate (eGFR) 15 mL/min/1.73m2 to 29 mL/min/1.73m2 or end stage renal disease (eGFR < 15 mL/min/1.73m2), adult patients with creatinine clearance (CLcr) 15 mL/min to 29 mL/min or end stage renal disease (CLcr < 15 mL/min)

Sites / Locations

National Institutes of Health Clinical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment

Arm Description

Patients receiving treatment

Outcomes

Primary Outcome Measures

The proportion of subjects achieving serum phosphate levels within the target range (Z-score -1 to +2) at Week 48

Serum phosphate is the primary driver of skeletal complications in patients with FGF23-mediated hypophosphatemia and has been correlated with poor clinical outcomes in patients with FD.

Secondary Outcome Measures

Change and percent change from baseline to post-baseline visits in serum phosphate, serum 1,25(OH)2D, ratio of renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR).

Safety endpoint for monitoring metabolic impact of burosumab in patients with FD.

Change in functional parameters: - Muscle strength - Range-of-motion - Walking speed (9-minute walk)

Outcome measures that reflect activities of daily living

Change in FD lesion histology and cell proliferation as assessed by minimally invasive bone biopsies from baseline to 48 weeks (adults with capacity to consent only) from baseline to 48 weeks

Safety endpoints to determine if burosumab impacts metabolic activity of FD lesions, which are a benign neoplastic process

Change from baseline to 48 weeks in patient reported outcomes measures: SF36, SF10, Brief Fatigue Inventory

Outcome measures to determine pain and health-related quality of life

Proportion of subjects achieving serum phosphate levels within the target range (Z-score -1 to +2) at Week 24.

Serum phosphate is the primary driver of skeletal complications in patients with FGF23-mediated hypophosphatemia and has been correlated with poor clinical outcomes in patients with FD.

Change and percent change in serum bone turnover markers, including procollagen 1 N-terminal propeptide (P1NP), beta crosslaps C-telopeptides (CTX), osteocalcin, and bone-specific alkaline phosphatase from baseline to 48 weeks.

Safety endpoints to determine if burosumab impacts metabolic activity of FD lesions, which are a benign neoplastic process

Adverse events and clinical safety laboratory tests for up to 4 weeks after the final burosumab dose

Safety endpoints for expected and unexpected adverse events

Change in FD lesion activity using 18F-NaF PET/CT total lesion activity

Safety endpoints to determine if burosumab impacts metabolic activity of FD lesions, which are a benign neoplastic process

Skeletal changes assessed on skeletal survey at baseline and 48 weeks

Safety endpoints to determine if burosumab impacts metabolic activity of FD lesions, which are a benign neoplastic process

Full Information

NCT ID

NCT05509595

First Posted

August 19, 2022

Last Updated

September 14, 2023

Sponsor

National Institute of Dental and Craniofacial Research (NIDCR)

1. Study Identification

Unique Protocol Identification Number

NCT05509595

Brief Title

Burosumab for Fibroblast Growth Factor-23 Mediated Hypophosphatemia in Fibrous Dysplasia

Official Title

A Phase 2 Study of Burosumab for Fibroblast Growth Factor-23 Mediated Hypophosphatemia in Fibrous Dysplasia

Study Type

Interventional

2. Study Status

Record Verification Date

September 13, 2023

Overall Recruitment Status

Recruiting

Study Start Date

December 7, 2022 (Actual)

Primary Completion Date

September 30, 2030 (Anticipated)

Study Completion Date

September 30, 2030 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Institute of Dental and Craniofacial Research (NIDCR)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

Background: Fibrous dysplasia (FD) is a disorder that affects bone growth. Affected bone tissue is weakened, and people with FD are prone to deformities, fractures, and other problems. People with FD may also have low blood phosphate levels. This can make bones even weaker. Better treatments are needed. Objective: To test a study drug (burosumab) in people with FD who have low blood phosphate levels. Eligibility: People aged 1 year or older who have FD and low blood phosphate levels. Design: Participants will visit the NIH 3 times in 48 weeks. Each visit will last 5 to 7 days. Participants will self-inject burosumab under the skin in their belly, upper arm, or thigh. They (or a caregiver) will do this at home 1 or 2 times a month. They will be trained in person on how to inject the drug. Home injections will be guided via telehealth. During NIH visits, participants will have a physical exam with blood and urine tests. They will have x-rays of different parts of their body. They will have a radioactive tracer injected into their vein; then they will have a bone scan. They will have tests to assess their strength, walking, and movement. They will complete questionnaires about their pain, mobility, and fatigue levels. Adult participants may have bone biopsies. These will be done under anesthesia with sedation. Small samples of FD-affected bone will be removed for study. Between NIH visits, participants will go to a local laboratory for blood and urine tests. Child participants will have an additional follow-up visit 2 weeks after the final NIH visit.

Detailed Description

Study Description: This will be a phase 2, open-label, single-arm study to evaluate the safety and efficacy of burosumab to normalize serum phosphate levels in subjects with fibrous dysplasia (FD) and fibroblast growth factor 23 (FGF23)-mediated hypophosphatemia. Objectives: Primary Objective: -Evaluate the efficacy of burosumab to normalize serum phosphate levels in subjects with FD and FGF23-mediated hypophosphatemia at 48 weeks. Secondary Objectives: Evaluate the efficacy of burosumab to normalize serum phosphate levels in subjects with FD and FGF23-mediated hypophosphatemia at 24 weeks. Evaluate the safety and tolerability of burosumab in patients with FD. Evaluate the effect of burosumab on increasing serum phosphate and additional mineral markers. Evaluate the impact of burosumab on FD lesion activity. Evaluate the effect of burosumab on functional parameters. Evaluate the effect of burosumab on pain and health-related quality of life. Endpoints: Primary Endpoint: -The proportion of subjects achieving serum phosphate levels within the target range (Z-score -1 to +2) at Week 48. Secondary Endpoints: Proportion of subjects achieving serum phosphate levels within the target range (Z-score -1 to +2) at Week 24. Adverse events and clinical safety laboratory tests for up to 4 weeks after the final burosumab dose (48 weeks for adult subjects, 50 weeks for pediatric subjects). Change and percent change from baseline to post-baseline visits in serum phosphate, serum 1,25(OH)2D, ratio of renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR). Change in FD lesion activity using 18F-NaF PET/CT total lesion activity from baseline to 48 weeks Change and percent change in serum bone turnover markers, including procollagen 1 N-terminal propeptide (P1NP), beta crosslaps C-telopeptides (CTX), osteocalcin, and bone-specific alkaline phosphatase from baseline to 48 weeks. Change in FD lesion histology and cell proliferation as assessed by minimally invasive bone biopsies from baseline to 48 weeks (adults with capacity to consent only) from baseline to 48 weeks Skeletal changes assessed on skeletal survey at baseline and 48 weeks Change from baseline to 48 weeks in: Muscle strength Range-of-motion Walking speed (9-minute walk) Change from baseline to 48 weeks in patient reported outcomes measures: SF36: adults SF10: children PROMIS Pain Intensity: Pediatric and Parent Proxy version 1.0, Adult version 2.0 PROMIS Pain Interference: Pediatric and Parent Proxy v 2.0, Adult v 1.1 PROMIS Mobility: Pediatric and Parent Proxy version 2.0, Adult Mobility Lower Extremity v 1.0 PROMIS Fatigue: Pediatric and Parent Proxy v 2.0, Adult FACIT 13a v1.0 Activities of Daily Living Questions: adults and children

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Fibrous Dysplasia Of Bone

Keywords

McCune-Albright Syndrome, Rickets, Osteomalacia, Metabolic Bone Disorders

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

15 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Treatment

Arm Type

Experimental

Arm Description

Patients receiving treatment

Intervention Type

Drug

Intervention Name(s)

Burosumab

Intervention Description

Human recombinant monoclonal antibody to fibroblast growth factor-23 (FGF23)

Primary Outcome Measure Information:

Title

The proportion of subjects achieving serum phosphate levels within the target range (Z-score -1 to +2) at Week 48

Description

Serum phosphate is the primary driver of skeletal complications in patients with FGF23-mediated hypophosphatemia and has been correlated with poor clinical outcomes in patients with FD.

Time Frame

48 weeks

Secondary Outcome Measure Information:

Title

Description

Safety endpoint for monitoring metabolic impact of burosumab in patients with FD.

Time Frame

48 weeks

Title

Change in functional parameters: - Muscle strength - Range-of-motion - Walking speed (9-minute walk)

Description

Outcome measures that reflect activities of daily living

Time Frame

48 weeks

Title

Change in FD lesion histology and cell proliferation as assessed by minimally invasive bone biopsies from baseline to 48 weeks (adults with capacity to consent only) from baseline to 48 weeks

Description

Safety endpoints to determine if burosumab impacts metabolic activity of FD lesions, which are a benign neoplastic process

Time Frame

48 weeks

Title

Change from baseline to 48 weeks in patient reported outcomes measures: SF36, SF10, Brief Fatigue Inventory

Description

Outcome measures to determine pain and health-related quality of life

Time Frame

48 weeks

Title

Proportion of subjects achieving serum phosphate levels within the target range (Z-score -1 to +2) at Week 24.

Description

Serum phosphate is the primary driver of skeletal complications in patients with FGF23-mediated hypophosphatemia and has been correlated with poor clinical outcomes in patients with FD.

Time Frame

24 weeks

Title

Description

Safety endpoints to determine if burosumab impacts metabolic activity of FD lesions, which are a benign neoplastic process

Time Frame

48 weeks

Title

Adverse events and clinical safety laboratory tests for up to 4 weeks after the final burosumab dose

Description

Safety endpoints for expected and unexpected adverse events

Time Frame

48 weeks (adults), 50 weeks (children)

Title

Change in FD lesion activity using 18F-NaF PET/CT total lesion activity

Description

Safety endpoints to determine if burosumab impacts metabolic activity of FD lesions, which are a benign neoplastic process

Time Frame

48 weeks

Title

Skeletal changes assessed on skeletal survey at baseline and 48 weeks

Description

Safety endpoints to determine if burosumab impacts metabolic activity of FD lesions, which are a benign neoplastic process

Time Frame

48 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

1 Year

Accepts Healthy Volunteers

Eligibility Criteria

INCLUSION CRITERIA: In order to be eligible to participate in this study, an individual must meet all of the following criteria: Confirmed diagnosis of fibrous dysplasia Serum phosphate <10th percentile for age and sex, AND intact serum FGF23 >=30 pg/mL Age >=1 year Provision of signed and dated informed consent/assent form Stated willingness of subject or Legally Authorized Representative (LAR) to comply with all study procedures and availability for the duration of the study For females of reproductive potential: agreement to use highly effective contraception for during study participation. Highly effective contraception methods include: Total abstinence (when this is in line with the preferred and usual lifestyle of the participant). Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. Male sterilization (at least 6 months prior to screening). For female participants on the study the vasectomized male partner should be the sole partner for that participant. Combination of the following (a+b or a+c, or b+c): Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception Placement of an intrauterine device (IUD) or intrauterine system (IUS) Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository For males of reproductive potential: use of condoms or other methods described above to ensure effective contraception with partner Minimum body weight of 7.5 kilograms EXCLUSION CRITERIA: An individual who meets any of the following criteria will be excluded from participation in this study: Pregnancy or lactation Known allergic reactions to burosumab or drug component Treatment with another investigational drug within 30 days of screening Treatment with burosumab within 30 days of screening Have any condition which in the opinion of the PI could present a concern for subject safety or difficulty with data interpretation Severe renal impairment or end stage renal disease, defined as: pediatric patients with estimated glomerular filtration rate (eGFR) 15 mL/min/1.73m2 to 29 mL/min/1.73m2 or end stage renal disease (eGFR < 15 mL/min/1.73m2), adult patients with creatinine clearance (CLcr) 15 mL/min to 29 mL/min or end stage renal disease (CLcr < 15 mL/min)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Olivia J de Jong, C.R.N.P.

Phone

(240) 595-2764

olivia.dejong@nih.gov

First Name & Middle Initial & Last Name or Official Title & Degree

Alison M Boyce, M.D.

Phone

(301) 827-4802

alison.boyce@nih.gov

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Alison M Boyce, M.D.

Organizational Affiliation

National Institute of Dental and Craniofacial Research (NIDCR)

Official's Role

Principal Investigator

Facility Information:

Facility Name

National Institutes of Health Clinical Center

City

Bethesda

State/Province

Maryland

ZIP/Postal Code

20892

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

Phone

800-411-1222

Ext

TTY dial 711

ccopr@nih.gov

12. IPD Sharing Statement

Plan to Share IPD

Undecided

IPD Sharing Plan Description

.The study team anticipates that all IPD that underlie results in a publication will be made available on reasonable request. The specifics of the timing and review process are in development.

Links:

URL

https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_000798-D.html

Description

NIH Clinical Center Detailed Web Page

Learn more about this trial

Burosumab for Fibroblast Growth Factor-23 Mediated Hypophosphatemia in Fibrous Dysplasia

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