A Dose Escalation Trial Evaluating Safety, Efficacy, and Pharmacokinetics of Multiple Subcutaneous Doses of TransCon CNP Administered Once Weekly in Children With Achondroplasia

NCT05246033 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: TCC-204
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 5

Brief Summary

Purpose of the study: The main purpose of this study is to determine the safety and evaluate the effect of a once weekly dose of TransCon CNP in prepubertal children with achondroplasia in China. Study Treatments: TransCon CNP is an investigational (new) drug, which means that it is currently being tested, and therefore is considered experimental. TransCon CNP is designed to provide a sustained exposure of active CNP by subcutaneous (under the skin) injection once weekly. The Randomized Period of this study is a double-blinded and placebo-controlled. "Placebo-controlled" means that some participants will receive injections that don't contain any TransCon CNP (placebo injection - no active ingredient). "Double-blinded" means that neither the participant nor the study doctor will know which treatment the participant will be receiving, except in an emergency. After completion of the Randomized Period the trial participant may be invited to take part of the Open-Label Period of this study. "Open-label" means that all participants will receive injections that contain TransCon CNP; regardless of which treatment (TransCon CNP or placebo) was assigned during the 52 weeks (1 year) Randomized Period/blinded treatment period. It also means that both the participant and the study doctor will know which treatment, and which dose the participant receives.

Conditions

Achondroplasia

Keywords

Achondroplasia; Dwarfism

Outcome Measures

Primary Outcomes (2)

• Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)

  Safety and tolerability of once weekly TransCon CNP treatment or placebo

  52 weeks

• Annualized height velocity (centimeters/year) at 52 weeks

  Annualized height velocity measured in centimeters over 52 weeks for TransCon CNP or placebo

  52 weeks

Study Arms (3)

TransCon CNP 50 mcg

EXPERIMENTAL

TransCon CNP 50 mcg CNP/kg or placebo mimicking TransCon CNP 50 mcg delivered once weekly by subcutaneous injection

Drug: TransCon CNP

TransCon CNP 100 mcg

EXPERIMENTAL

TransCon CNP 100 mcg CNP/kg or placebo mimicking TransCon CNP 100 mcg delivered once weekly by subcutaneous injection

Drug: TransCon CNP

Placebo

PLACEBO COMPARATOR

Placebo delivered once weekly by subcutaneous injection

Drug: Placebo for TransCon CNP

Interventions

TransCon CNP DRUG

TransCon CNP drug product is a lyophilized powder in a single-use vial containing either TransCon CNP 3.9 mg CNP-38/vial or TransCon CNP 0.80 mg CNP-38/vial. Prior to use, the lyophilized powder is reconstituted with sterile water for injection and administered by subcutaneous injection via syringe and needle.

TransCon CNP 100 mcg; TransCon CNP 50 mcg

Placebo for TransCon CNP DRUG

Weekly subcutaneously injection of placebo.

Placebo

Eligibility Criteria

• Age: 2 Years - 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Diagnosis of achondroplasia confirmed by genetic testing
• Age criteria: between ages 2 to 10 years old (inclusive) at Screening Visit
• Tanner stage 1 breast development for females or testicular volume \< 4ml for males at Screening
• Able to stand without assistance
• Parent/ legal guardian willing and able to administer subcutaneous injections of study medication
• Written, signed informed consent of the parent(s) or legal guardian(s) of the participant and written assent of the participant as required by the institutional review board/human research ethics committee/independent ethics committee (IRB/HREC/IEC)

You may not qualify if:

• 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 or severe hip pain or
• Otherwise are considered by the Investigator or Medical Monitor to make a participant unfit to receive investigational medicinal products or undergo trial related procedures
• Have received any dose of prescription medications intended to affect stature or body proportionality (including human growth hormone) in the 6 months prior to Screening (excluding nutritional supplements)
• Have received any investigational medicinal product or device intended to affect stature or body proportionality at any time
• History or presence of injury or disease of the growth plate(s), other than ACH, that affects growth potential of long bones
• History of any bone-related surgery that affects growth potential of long bones, such as orthopedic reconstructive surgery, including but not limited to:
• Foramen magnum decompression and laminectomy with full recovery are allowed with minimum of 6 months of bone healing
• Osteotomy to correct bowing is allowed with 12 months of bone healing
• Limb-lengthening with full recovery is allowed with a minimum of 12 months of bone healing
• History of 8 plate epiphysiodesis is allowed, but the plates must have been removed prior to Screening with minimum of 4 weeks of healing
• Have a growth disorder other than ACH that results in short stature or abnormal growth such as severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN), hypochondroplasia, growth hormone deficiency, Turner syndrome, or pseudoachondroplasia
• Have a medical condition that could result in short stature or abnormal growth such as inflammatory bowel disease, celiac disease, vitamin D deficiency, untreated hypothyroidism, or poorly controlled diabetes mellitus (HbA1c ≥8.0%), or other diabetic complications. Please note the following allowances:
• Vitamin D deficiency or insufficiency treated with supplementation is allowed. Vitamin D deficiency is defined as 25(OH)D level \<20ng/mL (\<49.9 nmol/L), insufficiency is defined as 25(OH)D level \<20-30ng/mL (49.92 - 74.86 nmol/L). Participants with Vitamin D deficiency or insufficiency must be on Vitamin D regimen before enrollment

Sponsors & Collaborators

• Ascendis Pharma A/S: lead

Study Sites (5)

Ascendis Pharma Investigational Site

Beijing, 100045, China

Location

Ascendis Pharma Investigational Site

Guangzhou, 510080, China

Location

Ascendis Pharma Investigational Site

Hangzhou, 310053, China

Location

Ascendis Pharma Investigational Site

Shanghai, 20082, China

Location

Ascendis Pharma Investigational Site

Wuhan, 430030, China

Location

MeSH Terms

Conditions

Achondroplasia; Dwarfism

Condition Hierarchy (Ancestors)

Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Osteochondrodysplasias; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Endocrine System Diseases

Study Officials

• Vibeke Breinholt

  Ascendis Pharma

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: There are 2 cohorts enrolling 24 subjects who will be randomized to receive either TransCon CNP or Placebo in a 3:1 ratio

Study Record Dates

• First Submitted: February 9, 2022
• First Posted: February 18, 2022
• Study Start: January 5, 2022
• Primary Completion: March 15, 2023
• Study Completion: March 1, 2024
• Last Updated: November 2, 2023

Record last verified: 2023-10

Locations

CN (5)