iid 2013 hsc final .pdf


Nom original: iid_2013_hsc_final.pdf
Titre: Style F 36 by 48
Auteur: Cindy Kranz

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Embryonic-like cell-secreted proteins induce hair growth
in a phase I/II trial in male pattern baldness
G. K. Naughton, M. Zimber, J. Peralta-Arambulo, T. Reyes-Cacas, M. Hubka, D. Ehrlich, J. Mansbridge

Introduction

Results

We have evaluated a bioengineered human cellderived formulation, termed Hair Stimulating
Complex (HSC), on the effects of hair growth activity
in male pattern baldness. HSC is produced by cells
grown on beads in hypoxic bioreactors and contains
cytokines including KGF, VEGF, and follistatin.
Follistatin antagonizes activin and BMPs which
maintain the quiescent state of hair follicle stem cell
proliferation.

HSC Significantly Increases Hair
Growth

A Phase I/II 56 patient trial conducted at two clinical
sites, with a similar protocol but with 8 injections of
HSC and control at baseline, and a repeat dose at
week 6, has passed the 12 week primary safety and
efficacy time point and has reached the final 48
week efficacy point. No severe product-related
adverse effects have been reported
and no
evidence of toxicity was observed in any of the
clinical indicators. In addition, statistical significance
was noted in all efficacy endpoints which include
increase in total hair count (p=0.0013), terminal hairs
(p=0.0135), vellus hairs (p=0.033) and cumulative
thickness density (p=0.0026).
The results seen with HSC represent a novel
regenerative medicine approach in hair growth
treatment.

3 month

S1016

Subjects Over 40 Years of Age
Subjects Age 40+
% Change from Baseline

Hair count + 35.88%
Terminal hair +
45.83%
Thickness + 42.76%

S2018

Increases seen across hair growth parameters.
Representative subject samples had notable
increases in total and terminal hair counts, as well
as hair thickness, as measured by Fotofinder
Trichoscan image analysis.

Increased Dose Results in Improved
Growth at 12 Weeks
16

*

14
12
10

46.5%

Total

Terminal

Vellus

12wk

19.35

39.11

15.67

24wk

13.39

16.96

17.26

36wk

12.67

20.97

9.96

Cosmetically
significant results
seen in subjects
40-59 years of age
in both trials.

Pilot Trial -Subjects Age 40+
% Change from Baseline

Total

Terminal

Vellus

12wk

8.52

21.94

5.09

24wk

5.42

12.88

-0.05

48wk

18.30

37.17

18.34

Robust growth in older subjects across
timepoints and hair growth parameters
broadens treatment potential. Unlike currently
available treatments which have efficacy limited to
younger patients in the earlier stages of hair loss,
cosmetically impactful hair growth was seen in
subjects over 40 in the Phase I/II and Pilot clinical
trials of HSC.

8
6
4

Temporal Recession Region

2
0
Honduras

Philippines

Pilot

Phase I/II

Temporal Recession

30

*p=0.0013

Phase I/II shows 46.5% greater increase in
total hair count as compared to the Pilot HSC
clinical trial at 12 weeks. Results indicate
improved efficacy with additional injections; 4 at
baseline in pilot trial as compared to 8 at
baseline and repeat dose at 6 weeks in Phase I/II.

25

20

15

Total Hair Count
Terminal Density

10

Vellus Density
5

0

12 Weeks

24 Weeks

36 Weeks

48 Weeks

-5

Methods

Rise in Terminal and Vellus Hairs
Supports Multiple Routes of
Activity

-10

HSC Phase I/II Clinical Trial – Adverse Events

**

28

HSC was released by QC on the basis of minimal values
of KGF, VEGF, and Follistatin as measured by ELISA. The
bioactivity of HSC is also assessed using a cell-based
bioassay.

Possible or Probable Relationship to Treatment

HSC
Baseline
+ 6 wks

Control
Baseline
+ 6 wks

% Change

Baseline

*

13

8

3

-2

Vellus Hair Count Terminal Hair Count
p=0.033

p=0.0135

Statistically significant increases in both
terminal and vellus hair counts was seen at
12 weeks. Growth of both terminal and vellus
hairs supports the hypothesis that HSC rescues
dormant follicles, in addition to converting vellus
to terminal hairs and increasing the number of
hairs per follicle.

48 Weeks

HSC treatment showed hair growth in the
temporal recession region at 12 weeks and
continuing through 48 weeks, with strong
efficacy in terminal hair count. Efficacy was
seen across treatment locations, including vertex,
mid-scalp and temporal recession in the Phase
I/II HSC clinical trial. Currently available hair loss
treatments have primarily shown efficacy in the
vertex region.

FST Bioactivity in HSC

Increase in Hair Thickness Indicates
Cosmetically Relevant Result
8.80

Cm Thickness Density (mm/cm2)

An independent analysis of macro photography was
performed by the TrichoScale Research Edition,
FotoFinder
Systems,
Inc.,
Columbia,
Maryland.
TrichoScale evaluation of images measured variables
including total hair count, hair shaft thickness and terminal
and vellus densities. The cutoff point for terminal hair
determination was 40 microns, a conservative measure
compared to the 30 micron cutoff in previous trials with
other hair growth products, Serum and urine samples were
obtained at the screening visit as well as the Week 4 and
Week 12 timepoints to assess liver, kidney, and bone
marrow toxicity, as well as testosterone levels.

18

*

8.60
8.40
8.20
8.00
7.80
7.60
7.40
7.20

Baseline
Single Treatment Site

Schematic illustrating treatment sites in Phase I/II
study. Subjects received 8 injections of HSC, spaced 3mm
apart, within a demarcated 1.2cm2 area, of the scalp and 8
injections of placebo in a separate 1.2cm2 area.

Clinical chemistry showed no indication of
toxicity or blood/urine abnormalities in the
general patient population following both sets
of HSC injection. Clinical evaluation of blood
serum chemistry, hematology and urinalysis
showed no changes from baseline over the course
of the treatment. Figures above show the serum
blood chemistry and hematology values obtained
at baseline (pre-treatment), 4 weeks and 12
weeks. No evidence of toxicity is observed in any
of the clinical indicators.

S2001 – Temporal Recession treatment area

23

The Phase I/II study consisted of 56 male subjects with
androgenetic alopecia receiving 8 x 0.1 cc intradermal
injections of HSC or placebo into one of two regions on the
scalp at baseline and at 6 weeks. Global photographs
and hair counts via macro photography (FotoFinderXpert
Clinical Trial System, FotoFinder Systems, Columbia,
Maryland), were performed at Baseline, Week 6, Week 12,
Week 24, Week 36 and Week 48. There were two
Investigators assigned at each site to use the
FotoFinderXpert Clinical Trial System.

HSC Safety Results

3 month
Hair count + 62.82%
Terminal hair +
79.74%
Thickness + 58.65%

% Change

We hypothesized that injection of this medium may
increase the supply of progenitor and transit
amplifying keratinocytes provided to the growing hair
shaft, leading to an increase in the thickness of the
hairs and a reversal of the miniaturization process.
The initial pilot study was a single site, double-blind,
randomized, placebo-controlled trial involving 26
males with androgenetic alopecia. At baseline one
area of the scalp received (4) 0.1cc intradermal
injections of HSC and the parallel site received
identical treatment with placebo. HSC showed an
excellent safety profile and a statistically significant
increase in hair shaft thickness (p<0.05) at 3 months
and hair density at 3 months (p <0.03) and 1 year
(p<0.03) as assessed by Trichoscan image analysis.
Increased terminal hairs were seen in the entire
region within the 4 injection sites supporting the
hypothesis that HSC stimulated resting and
miniaturizing follicles to increase terminal hair
growth.

Baseline

Efficacy in Difficult-to-Treat
Hair Loss Groups

12 Weeks

p=0.026

A statistically significant increase in hair
thickness density was seen at 12 weeks.
Increased hair thickness density results from: 1)
an increase in hair count, 2) an increase in the
number of terminal hairs and 3) an increase in hair
shaft diameter, all of which are important to
cosmetic impact.

Follistatin bioactivity of HSC inhibits the
activin-induced differentiation of K562 CML
cells. HSC decreases hemoglobin production in a
dose-dependent manner (HSC; blue plot) that is
specifically neutralized in the presence of antifollistatin antibodies (HSC-N; red plot).

Adverse Event

Severity

Number of
Subject
Experiencing

Scalp Pruritus/Itch

Mild

7

Resolved

Numbness/Hypoaest
hesia

Mild

2

Resolved

Fever/Pyrexia

Mild

2

Resolved

Wheals/Urticaria
(Rash)

Mild

1

Resolved

Body Malaise

Mild

1

Resolved

Seborrheic Dermatitis

Mild

3

2/3* Resolved

Outcome

* 1 case of seborrheic dermatitis outcome unknown

All adverse events were transient, mild and
quickly resolved. Of the small number of
subjects experiencing possibly treatment-related
adverse events, all events were mild and likely a
result of the injections themselves.

Conclusion
The safety and efficacy results seen with HSC in
this in-patient controlled human clinical trial
represent a novel regenerative medicine approach
in hair growth treatment by using bioengineered,
cell-derived growth factors, and substantiates
research around the activity of follistatin and other
factors
in
hair
growth
stimulation
and
maintenance. Initial safety and efficacy endpoints
at 12 weeks were achieved, with statistical
significance reached. The increased number of
injections and the second injection timepoint
resulted in an increase in terminal hairs that was
46.5% above the pilot clinical study. In addition,
unlike currently approved products, HSC induced
hair growth in the temporal recession as well as
vertex and mid scalp regions, and was highly
effective in men over 40 years of age. At the 48
week time point there continued to be a significant
increase in total hairs over baseline (p=0.028).
These results clearly demonstrate the safety and
efficacy of intradermal injections of HSC in
subjects with androgenetic alopecia.


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