Short StaturePhase 1/2NCT02636270
IGF-1 Treatment for Individuals With Short Stature Due to PAPP-A2 Deficiency
A Phase 1/2 study testing Increlex in people with Short Stature, run by Children's Hospital Medical Center, Cincinnati.
Trial summary
With this study we want to investigate the pharmacokinetic (PK) effect of a single injection of rhIGF-1 in patients with PAPP-A2 mutations compared to heterozygous carriers and healthy controls. Read more about this study
- Who is it for?
- Ages 10 years and olderHealthy volunteers can take part
- Conditions the study is for
- Short Stature
- What is being tested?
- Increlex
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- No sites listed yet
- Study dates
- 21 Dec 2015to 1 Dec 2022
- Phase
- Phase 1/2
- 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 10 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Defect in PAPP-A2 (heterozygous or homozygous mutation)
- Between the ages of 18 and 30
- In general good health
Who cannot join
- None
- Healthy Volunteers
- Any medications (with the exception of contraceptives)
- Pregnancy
About this study
Official title: Treatment With Recombinant Human Insulin-like Growth Factor 1 (rhIGF-1) in Patients With Pappalysin-2 (PAPP-A2) Gene Mutation.
With this study we want to investigate the pharmacokinetic (PK) effect of a single injection of rhIGF-1 in patients with PAPP-A2 mutations compared to heterozygous carriers and healthy controls. This will be followed by treatment of PAPP-A2 deficient patients with IGF-1 for a period of one-year to assess growth velocity. Additionally, we want to further describe the phenotypic characteristics of patients with PAPP-A2 deficiency.
Read the detailed description
The 24-hour pharmacokinetic response of free and total IGF-1 and IGF binding protein-3 (IGFBP-3) to a single dose of rhIGF-1 (120 mcg/kg) in three patients with PAPP-A2 mutation compared to up to four unaffected heterozygous relatives and 2 healthy adult controls.
One-year trial of rhIGF-1 at standard dose given to the two youngest males with PAPP-A2 mutation. The primary end point of this trial will be first year height velocity. Secondary outcomes will include height standard deviation score (SDS), height velocity, and whole body and lumbar spine bone mineral density assessment. The study was amended to extend the treatment period to continue until the subject has stopped growing (or elects to withdraw). All study procedures remain the same. Important note: the treatment phase continues to follow the youngest affected male. The older affected male developed an adverse event that resulted in discontinuation of treatment.
A post-treatment follow up visit (either in-person or remote) will be completed for the study participant who remained on Increlex approximately one-year after their discontinuation of therapy.
Description of additional phenotypic characteristics of patients with PAPP-A2 mutation will be studied by collecting information on glucose and insulin metabolism, body composition, bone geometry and bone density before and after treatment with rhIGF-1. These measures will be collected at the 12-month time period, and every year thereafter until the completion of the study. All three affected siblings will take part in the phenotyping activities.
- Conditions
- Short Stature
- Being tested
- Increlex
- Medical subject headings
- Dwarfism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IncrelexDrug
Also called rhIGF-1
Treat PAPP-A2 deficient patients with Increlex
| Study group | Role | What they receive |
|---|---|---|
| PAPP-A2 deficient patients | Experimental | Patients deficient in PAPP-A2 with short stature will be treated with Increlex (rhIGF-1) Receives: Drug: Increlex |
What is being measured
The primary outcome is the main question the study is designed to answer.
Height Velocity
Height velocity in a patient with PAPP-A2 deficiency treated with rhIGF-1 for five years (when the patient elected to discontinue treatment after reviewing growth velocity and skeletal maturation). Ultimately only one patient was treated for the study duration with results reported, as the other recruited participant (sibling of the treated patient) experienced pseudotumor cerebri and discontinued treatment after 51 days. He nevertheless was followed, with height velocity also reported.
Measured: Yearly until participant on treatment stops growing, or discontinues treatment (up to 6 years)
Secondary outcomes (2)
Height Standard Deviation Score
Height Standard Deviation Score is the standard deviation above or below the mean the height is for age and gender. Values were obtained by plotting heights on Centers for Disease Control and Prevention growth charts. An increase in Height Standard Deviation Score correlates with increase in height. Results are reported for the participant with PAPP-A2 deficiency treated with rhIGF-1, as well as sibling who did not continue treatment with rhIGF-1.
Measured: Annually until completion of study, up to 6 years
Pharmacokinetic/Pharmacodynamic (PK/PD) Relationship
Assess the PK/PD relationship (PD marker being IGFBP-3) annually while on treatment with rhIGF-1
Measured: Yearly until completion of the study, up to 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2015 (estimated)
- Study start21 Dec 2015
- Primary completion14 Oct 2022
- Study completion1 Dec 2022
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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Short StatureStudies of the same condition, open and under way.
- More trials run by Children's Hospital Medical Center, CincinnatiThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Philippe Backeljauw, MD, Principal investigator, Cincinnati Childrens HospitalGajanathan Muthuvel, MD, Principal investigator, Cincinnati Childrens Hospital Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02636270
- Sponsor's protocol ID
- 2015-6218
- Status last verified
- Feb 2024
- First submitted
- 10 Nov 2015
- Last updated
- 28 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: De-identifiable data may be shared with physician that is treating the only other two patients in the world with this genetic mutation.
Publications
Muthuvel G, Dauber A, Alexandrou E, Tyzinski L, Andrew M, Hwa V, Backeljauw P. Five-Year Therapy with Recombinant Human Insulin-Like Growth Factor-1 in a Patient with PAPP-A2 Deficiency. Horm Res Paediatr. 2023;96(5):449-457. doi: 10.1159/000529071. Epub 2023 Jan 16.
PubMed 36646053Cabrera-Salcedo C, Mizuno T, Tyzinski L, Andrew M, Vinks AA, Frystyk J, Wasserman H, Gordon CM, Hwa V, Backeljauw P, Dauber A. Pharmacokinetics of IGF-1 in PAPP-A2-Deficient Patients, Growth Response, and Effects on Glucose and Bone Density. J Clin Endocrinol Metab. 2017 Dec 1;102(12):4568-4577. doi: 10.1210/jc.2017-01411.
PubMed 29029190
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment With Recombinant Human Insulin-like Growth Factor 1 (rhIGF-1) in Patients With Pappalysin-2 (PAPP-A2) Gene Mutation.
- ClinicalTrials.gov ID
- NCT02636270
- Acronym / sponsor ID
- 2015-6218
- Conditions
- Short Stature
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Study start
- 21 Dec 2015 (actual)
- Primary completion
- 14 Oct 2022 (actual)
- Study completion
- 1 Dec 2022 (actual)
- First posted
- 21 Dec 2015 (estimated)
- Results
- Posted 28 Feb 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
With this study we want to investigate the pharmacokinetic (PK) effect of a single injection of rhIGF-1 in patients with PAPP-A2 mutations compared to heterozygous carriers and healthy controls. This will be followed by treatment of PAPP-A2 deficient patients with IGF-1 for a period of one-year to assess growth velocity. Additionally, we want to further describe the phenotypic characteristics of patients with PAPP-A2 deficiency.
Detailed description
The 24-hour pharmacokinetic response of free and total IGF-1 and IGF binding protein-3 (IGFBP-3) to a single dose of rhIGF-1 (120 mcg/kg) in three patients with PAPP-A2 mutation compared to up to four unaffected heterozygous relatives and 2 healthy adult controls.
One-year trial of rhIGF-1 at standard dose given to the two youngest males with PAPP-A2 mutation. The primary end point of this trial will be first year height velocity. Secondary outcomes will include height standard deviation score (SDS), height velocity, and whole body and lumbar spine bone mineral density assessment. The study was amended to extend the treatment period to continue until the subject has stopped growing (or elects to withdraw). All study procedures remain the same. Important note: the treatment phase continues to follow the youngest affected male. The older affected male developed an adverse event that resulted in discontinuation of treatment.
A post-treatment follow up visit (either in-person or remote) will be completed for the study participant who remained on Increlex approximately one-year after their discontinuation of therapy.
Description of additional phenotypic characteristics of patients with PAPP-A2 mutation will be studied by collecting information on glucose and insulin metabolism, body composition, bone geometry and bone density before and after treatment with rhIGF-1. These measures will be collected at the 12-month time period, and every year thereafter until the completion of the study. All three affected siblings will take part in the phenotyping activities.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PAPP-A2 deficient patients | Experimental | Drug: IncrelexPatients deficient in PAPP-A2 with short stature will be treated with Increlex (rhIGF-1) |
Who may qualify
- Ages
- 10 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Defect in PAPP-A2 (heterozygous or homozygous mutation)
- Between the ages of 18 and 30
- In general good health
Key exclusion criteria (4 listed)
- None
- Healthy Volunteers
- Any medications (with the exception of contraceptives)
- Pregnancy
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 |
|---|---|---|
| IncrelexAlso: rhIGF-1Treat PAPP-A2 deficient patients with Increlex | Drug | PAPP-A2 deficient patients |
Primary outcome
Height Velocity
Time frame: Yearly until participant on treatment stops growing, or discontinues treatment (up to 6 years)
Height velocity in a patient with PAPP-A2 deficiency treated with rhIGF-1 for five years (when the patient elected to discontinue treatment after reviewing growth velocity and skeletal maturation). Ultimately only one patient was treated for the study duration with results reported, as the other recruited participant (sibling of the treated patient) experienced pseudotumor cerebri and discontinued treatment after 51 days. He nevertheless was followed, with height velocity also reported.
2 secondary outcomes
Height Standard Deviation Score
Time frame: Annually until completion of study, up to 6 years
Pharmacokinetic/Pharmacodynamic (PK/PD) Relationship
Time frame: Yearly until completion of the study, up to 6 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 36646053Muthuvel G, Dauber A, Alexandrou E, Tyzinski L, Andrew M, Hwa V, Backeljauw P. Five-Year Therapy with Recombinant Human Insulin-Like Growth Factor-1 in a Patient with PAPP-A2 Deficiency. Horm Res Paediatr. 2023;96(5):449-457. doi: 10.1159/000529071. Epub 2023 Jan 16.
- Results publication: PubMed 29029190Cabrera-Salcedo C, Mizuno T, Tyzinski L, Andrew M, Vinks AA, Frystyk J, Wasserman H, Gordon CM, Hwa V, Backeljauw P, Dauber A. Pharmacokinetics of IGF-1 in PAPP-A2-Deficient Patients, Growth Response, and Effects on Glucose and Bone Density. J Clin Endocrinol Metab. 2017 Dec 1;102(12):4568-4577. doi: 10.1210/jc.2017-01411.
- Individual participant dataSharing planned: Yes. De-identifiable data may be shared with physician that is treating the only other two patients in the world with this genetic mutation.
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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.
Philippe Backeljauw, MD principal investigator
Cincinnati Childrens Hospital
Gajanathan Muthuvel, MD principal investigator
Cincinnati Childrens Hospital Medical Center
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Increlex in people with Short Stature, run by Children's Hospital Medical Center, Cincinnati.
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 3 inclusion and 4 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: finished, as of the sponsor's last update on 28 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 28 Feb 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?
Height Velocity (time frame: Yearly until participant on treatment stops growing, or discontinues treatment (up to 6 years)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02636270, which also lists 2 linked publications.
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 Feb 2024.