| Eligibility |
Inclusion Criteria:
1. Diagnosis of achondroplasia confirmed by genetic testing
2. Age criteria: between ages 2 to 10 years old (inclusive) at Screening Visit
3. Tanner stage 1 breast development for females or testicular volume < 4ml for males at
Screening
4. Able to stand without assistance
5. Parent/ legal guardian willing and able to administer subcutaneous injections of study
medication
6. 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)
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 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
2. 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)
3. Have received any investigational medicinal product or device intended to affect
stature or body proportionality at any time
4. History or presence of injury or disease of the growth plate(s), other than ACH, that
affects growth potential of long bones
5. 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
6. 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
7. 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
- Participants with hypothyroidism must be clinically euthyroid for 3 months prior
to enrollment and, in the opinion of the Investigator, have achieved any catch-up
growth expected from thyroxine replacement
- Participants with diabetes mellitus must have been on a stable medication regimen
for 3 months prior to enrollment (dose adjustments are allowed but addition or
discontinuation of medications in this time period is disallowed). In addition to
HbA1c <8.0%, any participant with diabetes must have adequate glycemic control in
the opinion of the Investigator and Medical Monitor to be considered a good
candidate for the trial
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 (iron deficiency anemia that is resolved or adequately treated in
the Investigator's opinion 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)
- 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 (within 2 months for fracture of
digits)
- Any disease or condition that, in the opinion of the Investigator or Medical
Monitor, may make the participant unlikely to fully complete the trial, may
confound interpretation of trial results, or may present undue risk from
receiving investigational product
10. 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 treatment (more
than twice/year) with oral corticosteroids during participation in the trial (low and
mid-dose inhaled corticosteroids are allowed with Medical Monitor approval. High-dose
inhaled corticosteroids are not allowed)
12. Use of medication known to prolong the QT/QTc interval (https://crediblemeds.org/.
Note: Only medications on the Known Risk list are excluded, not those on the Possible
or Conditional Risk lists). Prior use of such medications is allowed if participant
has sufficient wash-out period (minimum 7 days or 5 half-lives, whichever was longer)
and a normal QT/QTc interval on ECG.
13. Ongoing treatment with any medication that affects blood pressure or heart rate
14. Known hypersensitivity to the components of the investigational medicinal product
(trehalose, tris(hydroxymethyl)aminomethane, succinate and PEG)
15. Any other reason that in the opinion of the Investigator or Medical Monitor would
prevent the child from complying with the trial requirements, prevent successful
completion of the trial, or prevent successful interpretation of trial data • This
could include family situations, comorbid conditions, or medications that might impact
safety or be considered confounding
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