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Trial registered on ANZCTR


Registration number
ACTRN12619000318189
Ethics application status
Approved
Date submitted
20/02/2019
Date registered
1/03/2019
Date last updated
27/02/2020
Date data sharing statement initially provided
1/03/2019
Date results information initially provided
27/02/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Randomized, Double-Blind, Placebo-Controlled, Two-Part, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Effects of KER-050 Administered to Healthy, Postmenopausal Women.
Scientific title
Randomized, Double-Blind, Placebo-Controlled, Two-Part, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Effects of KER-050 Administered to Healthy, Postmenopausal Women.
Secondary ID [1] 297400 0
KER-050-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Muscular dystrophy 311557 0
Condition category
Condition code
Musculoskeletal 310193 310193 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 310344 310344 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Investigational product: KER-050 will be administered subcutaneously. Intervention adherence will be assessed by study monitors, this will be done by audit of nurses notes and pharmacy logs.
The study contains two parts.
1. Single ascending dose study (SAD), 4 cohorts of 10 participants randomised 4 (study drug): 1 (placebo).
Cohort 1: 0.05mg/kg single subcutaneous on day 1
Cohort 2: 0.5 mg/kg single subcutaneous on day 1
Cohort 3: 1.5mg/kg single subcutaneous on day 1
Cohort 4: 4.5 mg/kg single subcutaneous on day 1

2. Multiple ascending dose study (MAD) 4 cohorts of 10 participants randomised 4 (study drug): 1 (placebo).
Cohort 1: TBD* mg/kg subcutaneous on day 1, 15* and 29
Cohort 2: TBD* mg/kg subcutaneous on day 1, 15* and 29
Cohort 3: TBD* mg/kg subcutaneous on day 1, 15* and 29
Cohort 4: TBD* mg/kg subcutaneous on day 1, 15* and 29
(* specific dose levels and frequency to be confirmed following review of SAD data)


Intervention code [1] 313667 0
Treatment: Drugs
Comparator / control treatment
Placebo will be saline in an identical presentation to the Investigational product.
The placebo will be administered subcutaneously.
Control group
Placebo

Outcomes
Primary outcome [1] 319102 0
• Evaluate the safety and tolerability of escalating doses of KER-050 administered as single and multiple SC doses in healthy postmenopausal women;
To be assessed by monitoring
• Incidence and severity of AE;
• Incidence of serious adverse events (SAE) and suspected unexpected serious adverse reactions;
• Clinically significant changes from baseline in:
- Laboratory evaluations (hematology, chemistry, urinalysis, function tests);
- Electrocardiograms (ECG);
- Vital signs;
- Physical examinations;
- Anti-drug antibodies.
Timepoint [1] 319102 0
For the single ascending dose:
Safety is assessed at the following timepoints during the study: Screening, Day -1, Day 1, Day 2, Day 4, Day 7, Day 11, Day 15, Day 21, Day 29, Day 42, Day 63, Day 84.

For the multiple ascending dose:
Safety is assessed at the following timepoints during the study: Screening, Day -1, Day 1, Day 2, Day 4, Day 7, Day 11, Day 15,Day 16, Day 18, Day 21, Day 29, Day 30, Day 32, Day 35, Day 39, Day 42, Day 63, Day 84, Day 112.
Primary outcome [2] 319220 0
Blood samples will be collected to evaluate the PK profile following escalating doses of KER-050 administered as single and multiple SC doses.
To be assessed by calculating:
• Maximal concentration (Cmax);
• Time to maximum concentration (tmax);
• Area under the concentration-time curve from time 0 to last (AUC0-last);
• Area under the concentration-time curve from time 0 to infinity (AUC0-inf);
• Terminal elimination half-life (t1/2);
• Apparent clearance (Cl);
• Apparent volume of distribution (V).
Timepoint [2] 319220 0
For the single ascending dose:
• Day 1: within 30 minutes prior to start of injection;
• Day 2: 24 hours post dose (±30 minutes);
• Day 4: 72 hours post dose (±4 hours);
• Day 7: 6 days post dose (at the same nominal time of the day [±4 hours] as dose administration on Day 1);
• Day 11: 10 days post dose (anytime on Day 11);
• Day 15: 14 days post dose (±1 day);
• Day 21: 20 days post dose (±2 days);
• Day 29: 28 days post dose (±2 days);
• Day 42: 41 days post dose (±2 days);
• Day 63: 62 days post dose (±2 days);
• Day 84: 83 days post dose (±3 days).

For the multiple ascending dose:
• Day 1: within 30 minutes prior to start of injection;
• Day 2: 24 hours post dose (±30 minutes);
• Day 4: 72 hours post dose (±30 minutes);
• Day 7: 6 days post dose (at the same nominal time of the day [±3 hours] as dose administration on Day 1);
• Day 11: 10 days post dose (anytime on Day 11);
• Day 15: 14 days post dose (±1 day);
• Day 16 (only if Q2W): 15 days post dose; 1 day past second dose (±30 minutes);
• Day 18 (only if Q2W): 17 days post dose; 3 days past second dose (±30 minutes);
• Day 21: 20 days post dose (±2 days);
• Day 29: 28 days post dose (±2 days);
• Day 30: 29 days post dose; 1 day past last dose (±30 minutes);
• Day 32: 31 days post dose; 3 days past last dose (±30 minutes);
• Day 35: 34 days post dose (at the same nominal time of the day [±3 hours] as dose administration on Day 29);
• Day 39: 38 days post dose (anytime Day 39);
• Day 42: 41 days post dose (±2 days);
• Day 63: 62 days post dose (±2 days);
• Day 84: 83 days post dose (±3 days)
• Day 112: 111 days post dose (±5 days)

Secondary outcome [1] 366980 0
• Assess changes to serum FSH following escalating doses of KER-050 administered as single and multiple SC doses. This will be performed by collection blood for FSH evaluation.

Timepoint [1] 366980 0
SAD: Blood samples for FSH analysis will be collected at screening, D1, D2, D4, D7, D11, D15, D21, D29, D42, D63, D84.

MAD: Blood samples for FSH analysis will be collected at screening, D1, D2, D4, D7, D11, D15, D16, D18, D21, D29, D30, D32, D35, D39, D42, D63, D84 and Day 112 (or EOS)





Secondary outcome [2] 367349 0
• Assess changes to muscle tissue following escalating doses of KER-050: - Evaluate total body lean mass by full body dual energy x-ray absorptiometry (DXA) following escalating doses of KER-050 administered as multiple SC doses (Part 2 only)
Timepoint [2] 367349 0
Participants will undergo DXA at screening, Day 29, Day 63 and Day 112 (or EOS)
Secondary outcome [3] 367350 0
• Assess changes to bone tissue following escalating doses of KER-050: Changes to serum bone biomarkers following escalating doses of KER-050.

Blood will be collected for assessment of the following biomarkers:
• Follicle-stimulating hormone;
• Type I collagen telopeptide;
• Bone-specific alkaline phosphatase;
• Adiponectin;
• Leptin.
Timepoint [3] 367350 0
Biomarker assessment will occur on:

SAD: D1, D15, D29 and D63
MAD: D1, D15, D29 and D63
Secondary outcome [4] 367351 0
• Assess changes to adipose tissue following escalating doses of KER-050. The volume of the thigh adipose compartment as assessed by MRI scans following escalating doses of KER-050 administered as multiple SC doses (Part 2 only).
Timepoint [4] 367351 0
Participants will undergo MRI at screening, Day 29, Day 63 and Day 112 (or EOS).

Eligibility
Key inclusion criteria
1. Postmenopausal* female, aged 45 to 75 years (inclusive) at screening. *NOTE: Postmenopausal is defined as:
• 12 months of spontaneous amenorrhea, OR 6 months of spontaneous amenorrhea with serum FSH levels greater than 40 IU/L;
OR
• 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy;
2. Non-smoker or social smoker who agrees to smoke 8 or less cigarettes per week or is willing to abstain from smoking/nicotine products during the study;
3. Weight range within 50 kg to 110 kg (inclusive);
4. In good health as determined by review of medical history, physical examination, vital signs, oxygen saturation, clinical laboratory tests, 12-lead ECG, and any abnormal findings that are assessed as not clinically significant by the Investigator.
Minimum age
45 Years
Maximum age
75 Years
Gender
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Clinically significant (as determined by the Investigator) cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease;
2. History of or current malignancy (excluding basal cell carcinoma that has been resected with no evidence of metastatic disease for 3 years);
3. Chronic stable diseases including frequent migraines, type 2 diabetes, hypertension, hyperthyroid disorder, hypothyroid disorder, gastroesophageal reflux disease, or mild depression/anxiety;
4. Current opportunistic infection (eg, invasive candidiasis or pneumocystis pneumonia);
5. Serious local infection (eg, cellulitis, abscess) or systemic infection (eg, septicemia) within the 3 months prior to screening;
6. History of severe allergic or anaphylactic reactions;
7. Surgery within 3 months prior to screening (other than minor cosmetic surgery or minor dental procedures);
8. Fever (body temperature greater than 38°C) or symptomatic viral or bacterial infection within 2 weeks prior to screening that has not resolved prior to dosing;
9. Clinically relevant/significant laboratory findings (up to 2 repeats permitted) at screening including, but not limited to:
• Alanine transaminase and aspartate transaminase greater than or equal to 1.2 times the upper limit of normal (ULN), isolated and mainly unconjugated hyperbilirubinemia consistent with Gilbert's should not be excluded;
• Creatinine outside normal laboratory range;
• Serum creatine kinase greater than 1.5 times the ULN;

10. Donated blood (1 unit or more) within 1 month prior to dosing or plans to donate blood during the study;
11. Recent hormone replacement therapy, within 3 months prior to dosing or plans to begin hormone replacement therapy at any time during the study. Estrogen replacement is permitted;
12. Received systemic glucocorticoid therapy for more than 1 month within 6 months before screening;
13. Changes in medications that may affect muscle function (e.g. statins, beta-blockers, etc.) within 3 months prior to dosing;
14. Positive screen for alcohol and/or potential drugs of abuse (cannabis and metabolites, cocaine and metabolites, amphetamines, barbiturates, benzodiazepines and/or opioids) by urine drug screen at screening and Day -1. Up to 1 repeat permitted;
15. Treatment with another investigational drug, investigational device, or approved therapy for investigational use within 1 month or 7 half-lives prior to dosing;

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is concealed. The allocation will occur via numbered containers at the investigational product manufacturing facility as such they will be the holder of the allocation schedule.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computer-generated randomization schedule will be prepared by an unblinded statistician prior to the start of the study. Investigational product will be prepared in accordance with the randomization list.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
SAD cohorts: Subjects in each SAD cohort will be randomized in a ratio of 4:1 to KER-050 or placebo. Subjects will be screened and report to the study site over a 12 week period.
MAD cohorts: Subjects in each MAD cohort will be randomized in a ratio of 4:1 to KER-050 or placebo. Subjects will be screened and report to the study site over a 16 week period.
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis
There is no formal research hypothesis to be tested in this study. As such, no formal sample size calculations based on statistical power will be performed.

In general, data will be summarized using descriptive statistics (mean, median, standard deviation, minimum and maximum) or frequency counts and percentages, as appropriate to the type of data. Baseline will be defined as the last available, valid, non-missing assessment prior to dosing.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 13155 0
Nucleus Network - Melbourne
Recruitment hospital [2] 16007 0
Q-Pharm Pty - Clive Berghofer Research Centre (CBCRC) - Herston
Recruitment postcode(s) [1] 25709 0
3004 - Melbourne
Recruitment postcode(s) [2] 29517 0
4007 - Herston

Funding & Sponsors
Funding source category [1] 301972 0
Commercial sector/Industry
Name [1] 301972 0
Keros Therapeutics Australia Pty Ltd
Address [1] 301972 0
Floor 19, HWT Tower
40 City Road
Southbank, Vic, 3006
Country [1] 301972 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Keros Therapeutics Australia Pty Ltd
Address
Floor 19, HWT Tower
40 City Road
Southbank, Vic, 3006
Country
Australia
Secondary sponsor category [1] 301829 0
None
Name [1] 301829 0
Address [1] 301829 0
Country [1] 301829 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302652 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 302652 0
55 Commercial Road Melbourne VIC 3004
Ethics committee country [1] 302652 0
Australia
Date submitted for ethics approval [1] 302652 0
27/02/2019
Approval date [1] 302652 0
02/04/2019
Ethics approval number [1] 302652 0

Summary
Brief summary
KER-050 is a muscle anabolic agent proposed to increase muscle mass and strength and is in development for the treatment of Duchenne muscular dystrophy (DMD) and facioscapulohumeral muscular dystrophy (FSHD).
Duchenne muscular dystrophy is the most common form of muscular dystrophy and is estimated to affect 1 in every 3500 males globally. FSHD is one of the most prevalent adult forms of muscular dystrophy and can also affect children. The study hypothesis is that Ker-050 is safe to administer to participants and provides an indication that has an effect on the growth of adipose tissue and bone.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 90938 0
Dr Ben Snyder
Address 90938 0
Nucleus Network
Level 1/484 ST Kilda Road Melbourne Victoria 3004.
Country 90938 0
Australia
Phone 90938 0
+61 3 8593 9835
Fax 90938 0
Email 90938 0
b.snyder@nucleusnetwork.com.au
Contact person for public queries
Name 90939 0
Dr Ben Snyder
Address 90939 0
Nucleus Network
Level 1/484 ST Kilda Road Melbourne Victoria 3004.
Country 90939 0
Australia
Phone 90939 0
+61 3 8593 9835
Fax 90939 0
Email 90939 0
b.snyder@nucleusnetwork.com.au
Contact person for scientific queries
Name 90940 0
Dr Ben Snyder
Address 90940 0
Nucleus Network
Level 1/484 ST Kilda Road Melbourne Victoria 3004.
Country 90940 0
Australia
Phone 90940 0
+61 3 8593 9835
Fax 90940 0
Email 90940 0
b.snyder@nucleusnetwork.com.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual participant data will not be available. data will be analyzed by group and descriptive statistics generated.
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary