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IGF-1 Treatment for Individuals With Short Stature Due to PAPP-A2 Deficiency

Sponsor
Children's Hospital Medical Center, Cincinnati (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT02636270
Collaborator
(none)
7
Enrollment
1
Arm
83
Anticipated Duration (Months)

Study Details

Study Description

Brief 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. 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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

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 change in height SDS, change in height velocity SDS, and change in whole body and lumbar spine bone mineral density. The study was amended to extend the treatment period to continue until the subject has stopped growing. 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

Study Type:
Interventional
Actual Enrollment :
7 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Treatment With Recombinant Human Insulin-like Growth Factor 1 (rhIGF-1) in Patients With Pappalysin-2 (PAPP-A2) Gene Mutation.
Actual Study Start Date :
Dec 1, 2015
Anticipated Primary Completion Date :
Aug 31, 2022
Anticipated Study Completion Date :
Nov 1, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: PAPP-A2 deficient patients

Patients deficient in PAPP-A2 with short stature will be treated with Increlex (rhIGF-1)

Drug: Increlex
Treat PAPP-A2 deficient patients with Increlex
Other Names:
  • rhIGF-1

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Improve growth velocity [Yearly until participant on treatment stops growing, up to 6 years]

      Increase in participants height

    Secondary Outcome Measures

    1. Pharmacokinetic/Pharmacodynamic (PK/PD) relationship [Yearly until completion of the study, up to 6 years]

      Assess the PK/PD relationship (PD marker being IGFBP-3) during the one year of treatment and until completion of the study

    Other Outcome Measures

    1. Change from pre-treatment in glucose [Yearly until completion of the study, up to 6 years]

      Observe nonparametric measures of glucose in each individual pre and post treatment

    2. Change from pre-treatment in insulin metabolism [Yearly until completion of the study, up to 6 years]

      Observe nonparametric measures of insulin metabolism in each individual pre and post treatment

    3. Change from pre-treatment in body composition [Yearly until completion of the study, up to 6 years]

      Observe nonparametric measures of body composition in each individual pre and post treatment

    4. Change from pre-treatment in bone geometry [1 Year]

      Observe nonparametric measures of bone geometry in each individual pre and post treatment

    5. Change from pre-treatment in bone density [Yearly until completion of the study, up to 6 years]

      Observe nonparametric measures of bone density in each individual pre and post treatment

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    10 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes

    PAPP-A2 deficient

    Inclusion Criteria:
    • Defect in PAPP-A2 (heterozygous or homozygous mutation)
    Exclusion Criteria:
    • None

    Healthy Volunteers

    Inclusion Criteria:

    • Between the ages of 18 and 30

    • In general good health

    Exclusion Criteria:

    • Any medications (with the exception of contraceptives)

    • Pregnancy

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Children's Hospital Medical Center, Cincinnati

    Investigators

    • Principal Investigator: Philippe Backeljauw, MD, Cincinnati Childrens Hospital

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Children's Hospital Medical Center, Cincinnati
    ClinicalTrials.gov Identifier:
    NCT02636270
    Other Study ID Numbers:
    • 2015-6218
    First Posted:
    Dec 21, 2015
    Last Update Posted:
    Jul 19, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Additional relevant MeSH terms:
    Dwarfism
    Mecasermin

    Study Results

    No Results Posted as of Jul 19, 2022