AttaCH: A Phase 2, Multicenter, Long-Term, Open Label Extension Trial Evaluating Safety, Tolerability, and Efficacy of Subcutaneous Doses of TransCon CNP Administered Once Weekly in Children and Adolescents with Achondroplasia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ascendis Pharma Growth Disorders A/S

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

6 Jul 2023 → ongoing

Decision date (initial)

2023-09-04

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Ascendis Pharma Growth Disorders A/S, Denmark

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate safety and tolerability of long-term use of TransCon CNP and
To evaluate sustained efficacy of TransCon CNP on growth

Secondary objectives 4

1. To evaluate sustained efficacy of long-term treatment with navepegritide on growth
2. To evaluate safety and tolerability of long-term treatment with navepegritide
3. To evaluate pharmacokinetic properties of navepegritide
4. To assess potential immunogenic response to navepegritide

Conditions and MedDRA coding

Achondroplasia in Children and Adolescents

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002689-PIP02-03

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

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). For participants who are below the age of consent, a written assent will be obtained in accordance with applicable requirements as required by IRB/HREC/IEC. Upon reaching the legal age of consent, depending on applicable requirements, these participants will be asked to give their own written consent.
2. Participants with achondroplasia who have completed a clinical trial with TransCon CNP.
3. Parent(s)/legal guardian(s) willing and able to administer weekly SC injections of TransCon CNP and to follow the protocol.
4. Considered eligible based on the safety evaluations performed for evaluating stopping/holding rule criteria during the prior TransCon CNP clinical trial.

Exclusion criteria 6

1. Known or suspected hypersensitivity to the investigational product or related products (trehalose, tris[hydroxymethyl]aminomethane, succinate, and methoxy polyethylene glycol [mPEG]).
2. Have received any dose of prescription medications, investigational medicinal product (other than TransCon CNP).
3. Sexually active female participants and female partners of male participants of childbearing potential not using a highly effective form of contraceptive (including oral, injectable, or implantable contraception, or intrauterine device (IUD) for the entire trial period and for 90 days post end of the trial.
4. Participants with serum 25-hydroxy-vitamin D (25OHD) levels of <50 nmol/L (<20 ng/mL) at Visit 1 not on a treatment regimen of Vitamin D supplementation.
5. 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 may present undue risk from receiving trial treatment. This could include family situations, complications or manifestations, or medications that might impact safety or be considered confounding.
6. Closed femur and tibial epiphysis.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Incidence of treatment emergent adverse events (TEAEs) [Time Frame: Through trial completion]
2. Height Z-scores [Time Frame: Through trial completion]

Secondary endpoints 5

1. Annualized growth velocity (AGV) (cm/year)
2. Near final adult height [Time Frame: Through trial completion]
3. Safety assessments: • Laboratory results of safety blood parameters • Vital signs (BP, HR, body temperature) • Abnormal physical examination findings • 12-lead electrocardiogram (ECG) • Tanner stage • Imaging assessments of bone age and bone related safety events (e.g. fracture, skeletal deformities, joint damage, slipped capital femoral epiphysis, avascular necrosis and osteonecrosis) • Tolerability and acceptability [Time Frame: Through trial completion]
4. Plasma concentrations of Total CNP, Free CNP, and mPEG [Time Frame: Through treatment completion]
5. Detection and analysis of anti-drug antibodies (ADAs) [Time Frame: Through trial completion]

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ascendis Pharma Growth Disorders A/S

Sponsor organisation

Ascendis Pharma Growth Disorders A/S

Address

Tuborg Boulevard 12

City

Hellerup

Postcode

2900

Country

Denmark

Scientific contact point

Organisation

Ascendis Pharma Growth Disorders A/S

Contact name

Clinical Trial Information Desk

Public contact point

Organisation

Ascendis Pharma Growth Disorders A/S

Contact name

Clinical Trial Information Desk

Third parties 11

Locations

10 EU/EEA countries · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 301 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

20 submissions — initial application plus substantial / non-substantial modifications