Achondroplasia (ACH) in prepubertal children MedDRA version: 25.0 Level: LLT Classification code 10000452 Term: Achondroplasia System Organ Class: 10010331 - Congenital, familial and genetic disorders
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 T
Sponsors
Ascendis Pharma Growth Disorders A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the trial only if all of the following criteria apply: 1. Written, signed informed consent of the parent(s) or legal guardian(s) of the participant, and as required by the institutional review board/human research ethics committee/independent ethics committee (IRB/HREC/IEC). 2. Male or female, between 2 and 11 years of age (inclusive) at the time of Screening. 3. Clinical diagnosis of ACH with documented genetic confirmation available. 4. Able to stand without assistance. 5. Parent(s)/legal guardian(s) willing and able to administer weekly SC injections of IMP and to follow the protocol. 6. At least six months of growth and disease history from ACHieve (TCC-NHS-01) trial or comparable growth and disease history available from medical records (pending confirmation by Medical Monitor). 7. Considered eligible based on the medical history, physical examination, and the results of vital signs, ECG and clinical laboratory tests performed during the Screening period. Are the trial subjects under 18? yes Number of subjects for this age range: 80 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Participants are excluded from the trial if any of the following criteria apply: 1. Participation (i.e., signed informed consent) in any interventional clinical trial before within 3 months prior to screening. 2. Closed epiphysis. 3. Known or suspected hypersensitivity to the IMP or related products (trehalose, tris[hydroxymethyl]aminomethane, succinate, and mPEG). 4. Have a growth disorder or medical condition other than ACH that results in short stature or abnormal growth such as severe ACH with developmental delay and acanthosis nigricans (SADDAN), hypochondroplasia, growth hormone deficiency, Turner syndrome, pseudoachondroplasia, inflammatory bowel disease, celiac disease, hypothyroidism, hyperthyroidism, pre-diabetes, or diabetes mellitus. 5. Have received any dose of prescription medications and IMP or surgical intervention intended to affect stature, growth, or body proportionality at any time. 6. Requires, or anticipated to require, chronic (> 4 weeks) or repeated treatment (more than twice/year and >3 weeks/year) with systemic corticosteroids during participation in the trial. Chronic use of high-dose inhaled corticosteroids is not allowed. 7. Known history of presence of injury or disease of the growth plate(s), other than ACH, that affects growth potential of long bones. 8. Known history of any bone-related surgery affecting growth potential of long bones, such as: • Orthopedic reconstructive surgery for bone lengthening (e.g., procedures for leg bowing such as 8-plate are not exclusionary). • Cervicomedullary decompression surgery without anticipated need for repeat decompression during the time of the trial are allowed with minimum of 6 months of bone healing. • Ventriculoperitoneal (VP) shunt and laminectomy with full recovery are allowed with minimum of 6 months of bone healing. • Bone fracture within 6 months prior to screening (within 2 months for fracture of digits and buckle fractures). 9. Clinically significant findings at Screening, such as: • Expected to require surgical intervention during participation in the trial. Common surgeries, such as insertion of grommets, adenoidectomy, tonsillectomy, or myringotomy tube placement, are permitted. • Severe untreated sleep apnea or newly initiated sleep apnea treatment (e.g., Continuous Positive Airway Pressure [CPAP] in the previous 2 months prior to Screening. • Musculoskeletal disease, such as Salter-Harris fractures or clinical and/or radiographic evidence of severe hip pathology, or • Otherwise, are considered by the Investigator and Medical Monitor to make a participant unfit to receive trial treatment or undergo trial related procedures. 10. Have evidence at Screening that are consistent with severe cervicomedullary junction compression based on clinical and/or radiologic findings that indicate immediate surgical intervention is required. 11. Have a clinically significant finding or arrhythmia as determined by the investigator in consultation with the medical monitor that indicates abnormal cardiac function or conduction that includes, but is not exclusive to: • Repaired or unrepaired coarctation. • Moderate or greater complexity congenital heart disease including tetralogy of Fallot, Atrioventricular septal defects, truncus arteriosus, total anomalous pulmonary venous return, double outlet right ventricle, or single ventricle heart disease. 12. QTcF = 450 msec at the Screening Visit. 13. Known history or presence of condition that impacts hemodynamic stability (s
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate efficacy of TransCon CNP on growth;Secondary Objective: • To evaluate efficacy of TransCon CNP on growth • To evaluate the treatment impact of TransCon CNP on spinal curvature • To evaluate the treatment impact of TransCon CNP on health-related quality of life ;Primary end point(s): AGV at Week 52;Timepoint(s) of evaluation of this end point: Annualized growth velocity (AGV) will be evaluated at Week 52 | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: • Change from baseline in height Z-score will be evaluated at week 52 • Incidence of TEAEs will be evaluated at each visit and safety assessments (safety labs, vital signs, physical examination, 12-lead ECG, and radiographic assessments) will be evaluated, dependant on procedure, at screening and weeks 0, 4, 12, 26, 39, 52, 56, 64, 78, 91, 104 and 109 • Plasma concentration of Total, Free CNP and mPEG will be evaluted at weeks 4, 12, 26, 39, 52, 56, 64, 78, 91 and 104 • Detection and characterisation of ADAs will be evaluated at weeks 0, 4, 12, 26, 39, 52, 56, 64, 78, 91, 104 and 109;Secondary end point(s): • Change from baseline in height Z-score at Week 52 • Change from baseline in TLK ACH-specific Z-score at Week 52 • Change from baseline in the SF-10 PHS score at Week 52 Change from baseline in the following ACEM scores at Week 52: • ACEM-PF • ACEM-DF • ACEM-OSM | — |
Countries
Australia, Canada, Denmark, Ireland, New Zealand, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trial Information Desk
Ascendis Pharma A/S
Outcome results
None listed