Achondroplasia (ACH) in prepubertal children MedDRA version: 20.0 Level: LLT Classification code 10000452 Term: Achondroplasia System Organ Class: 100000004850
Conditions
Interventions
Product Name: TransCon CNP 3.9 mg CNP-38/vial
Product Code: TransCon CNP
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: C-TYPE NATRIURETIC PEPTIDE CONJUGATED
Sponsors
Ascendis Pharma Growth Disorders A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Clinical diagnosis of ACH with genetic confirmation 2. Age between 2 to 10 years old (inclusive) at Screening Visit 3. Prepubertal (Stage 1 breasts for girls or testicular volume =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Clinically significant findings at Screening that: •are expected to require surgical intervention during participation in the trial or •are musculoskeletal in nature, such as Salter-Harris fractures and severe hip pain or •otherwise are considered by investigator or Medical Monitor to make a participant unfit to receive study drug or undergo trial related procedures 2.Have received treatment (>3 months) of human growth hormone (hGH) or other medications known to affect stature or body proportionality at any time 3.Have received any dose of medications intended to affect stature or body proportionality within the previous 6 months of Screening Visit 4.Have received any study drug or device intended to affect stature or body proportionality at any time 5.History or presence of injury or disease of the growth plate(s), other than ACH, that affects growth potential of long bones 6.History of any bone-related surgery that affects growth potential of long bones, such as orthopedic reconstructive urgery and osteotomy (Limb-lengthening with full recovery is allowed with a minimum of 12 months of bone healing. Foramen magnum decompression and laminectomy with full recovery are allowed with minimum of 6 months of bone healing. History of 8 plate epiphysiodesis is allowed, but the plates must have been removed prior to Screening with minimum 4 weeks of healing). 7.Have a form of skeletal dysplasia other than ACH or known medical conditions that result in short stature or abnormal growth. 8.History or presence of malignant disease, other than basal cell epithelioma/carcinoma or completely resected squamous skin cancer with no recurrence for 12 months per medical records 9.History or presence of the following: •Chronic anemia (resolved iron deficiency anemia is allowed) •Significant cardiovascular disease per the judgement of the investigator, such as congenital heart disease (uncomplicated patent ductus arteriosus and atrial or ventricular septal defect with repair are allowed), aortic insufficiency, clinically significant arrhythmias, congestive heart failure with NYHA class II and above, or other conditions that impair regulation of blood pressure or heart rate •Condition that impacts hemodynamic stability (such as autonomic dysfunction, orthostatic intolerance) •History of chronic renal insufficiency •Chronic or recurrent illness that can affect hydration or volume status. This may include conditions associated with decreased nutritional intake or increased volume loss •Bone fracture within 6 months prior to Screening Visit (within 2 months for fracture of digits) •Any disease or condition that, in the opinion of the investigator, may make the participant unlikely to fully complete the trial, may confound interpretation of trial results, or presents undue risk from receiving study drug 10.Child has significant electrocardiogram abnormalities, including evidence of a previous myocardial infarction, left ventricular hypertrophy, flat T waves (particularly in the inferior leads) or more than minor non-specific ST-T wave changes or: •QRS>90 milliseconds (msec) •QT interval corrected using Fridericia's formula (QTcF)>440 msec •PR interval>170 msec •Complete right or left bundle branch block 11.Requires, or anticipated to require, chronic (>4 weeks) or repeated (more than twice per year) treatment with oral corticosteroids during participation in the trial (low and mid-dose inhaled corticosteroids are allowed. High-dose inhaled corticosteroids are
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Efficacy will be evaluated at 52 weeks but safety and PK will be evaluated at 52 weeks and during the open label extension;Main Objective: In prepubertal children with achondroplasia (ACH) at 52 weeks • To determine the safety of once weekly subcutaneous (SC) doses of TransCon CNP • To evaluate the effect of once weekly SC doses of TransCon CNP on annualized height velocity (AHV);Secondary Objective: • To evaluate the effect of once weekly SC doses of TransCon CNP on body proportionality (upper to lower body segment ratio) in prepubertal children with ACH at 52 weeks. • To evaluate the pharmacokinetic (PK) properties of once weekly SC doses of TransCon CNP • To assess the potential immunogenic response to once weekly SC doses of TransCon CNP;Primary end point(s): Safety Endpoints The following safety endpoints will be assessed for both blinded Randomized Period and Open-Label Extension Period: • Incidence of AEs • All blood chemistry, hematology, lipid panel, and urinalysis parameters • Vital sign measurements and physical examination assessments • 12-lead ECG • Radiographic findings from: - Bone age X-ray - DXA - AP standing lower extremity X-ray - AP and lateral spine X-ray • Incidence of anti-drug antibodies Efficacy Endpoints • AHV as measured at 52 weeks of weekly TransCon CNP treatment or placebo Pharmacokinetic Endpoints • Plasma concentration of Total CNP • Plasma concentration of Free CNP • Plasma concentration of mPEG and mPEG-linker | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Change in upper to lower body segment ratio as measured at 52 weeks of weekly TransCon CNP treatment or placebo ;Timepoint(s) of evaluation of this end point: At 52 weeks of weekly TransCon CNP treatment or placebo | — |
Countries
Australia, Austria, Canada, Denmark, Germany, Ireland, New Zealand, Portugal, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactClinical Trial Information Desk
Ascendis Pharma A/S
Outcome results
None listed